Radiopharmaceuticals operate by combining radionuclides with carriers.The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues.In c...Radiopharmaceuticals operate by combining radionuclides with carriers.The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues.In comparison to external beam radiation therapy,radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity.This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment.Several key radionuclides are examined,including^(223)Ra,^(90)Y,Lutetium-177(^(177)Lu),212 Pb,and Actinium-225(^(225)Ac).It also explores the current development trends of radiopharmaceuticals,encompassing the introduction of novel radionuclides,advancements in imaging technologies,integrated diagnosis and treatment approaches,and equipment-medication combinations.We review the progress in the development of new treatments,such as neutron capture therapy,proton therapy,and heavy ion therapy.Furthermore,we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.展开更多
1|INTRODUCTION Cancer has emerged as a significant threat to human life,and its incidence and mortality are increasing rapidly.As clinicians increasingly seek to noninvasively investigate tumor phenotypes and evaluate...1|INTRODUCTION Cancer has emerged as a significant threat to human life,and its incidence and mortality are increasing rapidly.As clinicians increasingly seek to noninvasively investigate tumor phenotypes and evaluate functional and molecular responses to therapy,the combination of diagnostic im-aging with targeted therapy is becoming more widely implemented[1].Targeted radionuclide therapy involves the use of small molecules,peptides,and/or antibodies as carriers for therapeutic radionuclides,with these being referred to as radiopharmaceuticals.Radiopharmaceuti-cals,also known as molecular probes in nuclear medicine,play a vital role in clinical diagnosis and therapy.Currently,there are numerous radiopharmaceuticals approved or under research worldwide for a wide range of indications.At the end of March 2022,there were 60 radiopharmaceuticals approved for marketing by the Food and Drug Administration(FDA)[2](Supplemental Table)[2].As of October 2023,42 radiopharmaceuticals have been approved for marketing by the National Medical Products Administration(NMPA)[3].However,there remains an urgent need to identify new targets and new drug molecules to advance the process of radiopharma-ceutical research and development.展开更多
Astatine-211(^(211)At,t_(1/2)=7.21 h)emitting twoαparticles with energies of 5.87 and 7.45 MeV,can lead to a high linear energy transfer(LET=98.84 ke V/μm)and short tissue range(50~90μm).Since the 1950s,^(211)At ha...Astatine-211(^(211)At,t_(1/2)=7.21 h)emitting twoαparticles with energies of 5.87 and 7.45 MeV,can lead to a high linear energy transfer(LET=98.84 ke V/μm)and short tissue range(50~90μm).Since the 1950s,^(211)At had stepped into endoradiotherapy and has always been regarded as one of the most promisingα-emitters for targeted-alpha therapy(TAT)in various malignancies.In the past two decades,^(211)At related radiopharmaceuticals have achieved great progress in the studies of basic physicochemical properties of astatine,^(211)At labeling strategies,preclinical and clinical studies,producing profound effects in nuclear medicine.This work will give a panorama of^(211)At-related researches in the recent 20 years,which will cover both the fundamental insights of^(211)At radiochemistry and applied labeling compounds.It can provide some important hints for the studies of TAT and other radiopharmaceuticals applied in tumor radiotherapy.展开更多
Samarium-153- EDTMP (ethylene diamine tetramethylene phosphonate), for its promising biological properties, has been proved as a palliating therapeutic agent for bone tumor in human beings. 153Sin with high radionucl...Samarium-153- EDTMP (ethylene diamine tetramethylene phosphonate), for its promising biological properties, has been proved as a palliating therapeutic agent for bone tumor in human beings. 153Sin with high radionuclear purity and specific activity of 5.18 GBq (140 mCi)/mg Sm2O3 was prepared by irradiating naturalSm2O3(152Sm, 26.7%) sample, replacing costly enriched samarium oxide target, at a flux of 4x 1013n.cm-2.s-1 for 110 h. The yield of 153Sm complexing with EDTMP is greater than 98% at PH 8￣10 in boiling water bath for 30 min, and not significantly decreases within one week after 153Sm-EDTMP complex formation.展开更多
Genetic heterogeneity and chemotherapy-resistant ＇stem cells＇ represent two of the most pressing issues in devising new strategies for the treatment of advanced prostate cancer. Though curative strategies have long ...Genetic heterogeneity and chemotherapy-resistant ＇stem cells＇ represent two of the most pressing issues in devising new strategies for the treatment of advanced prostate cancer. Though curative strategies have long been present for men with localized disease, metastatic prostate cancer is currently incurable. Though substantial improvements in outcomes are now possible through the utilization of newly approved therapies, novel combinations are clearly needed. Herein we describe potentially synergistic interactions between bone stromal-targeted radiopharmaceuticals and other therapies for treatment of bone-metastatic prostate cancer. Radiation has long been known to synergize with cytotoxic chemotherapies and recent data also suggest the possibility of synergy when combining radiation and immune-based strategies. Combination therapies will be required to substantially improve survival for men with castrate-resistant metastatic prostate cancer and we hypothesize that bone-targeted radiopharmaceuticals will play an important role in this Drocess.展开更多
Pancreatic cancer(PC) is a major health problem. Conventional imaging modalities show limited accuracy for reliable assessment of the tumor. Recent researches suggest that molecular imaging techniques with tracers pro...Pancreatic cancer(PC) is a major health problem. Conventional imaging modalities show limited accuracy for reliable assessment of the tumor. Recent researches suggest that molecular imaging techniques with tracers provide more biologically relevant information and are benefit for the diagnosis of the cancer. In addition,radiopharmaceuticals also play more important roles in treatment of the disease. This review summaries the advancement of the radiolabeled compounds in the theranostics of PC.展开更多
Nuclear medicine plays an irreplaceable role in the diagnosis and treatment of tumors.Radiopharmaceuticals are important components of nuclear medicine.Among the radiopharmaceuticals approved by the Food and Drug Admi...Nuclear medicine plays an irreplaceable role in the diagnosis and treatment of tumors.Radiopharmaceuticals are important components of nuclear medicine.Among the radiopharmaceuticals approved by the Food and Drug Administration(FDA),radio-tracers targeting prostate-specific membrane antigen(PSMA)and somatostatin receptor(SSTR)have held essential positions in the diagnosis and treatment of prostate cancers and neuroendocrine neoplasms,respectively.In recent years,FDA-approved serials of immune-therapy and targeted therapy drugs targeting programmed death 1(PD-1)/programmed death ligand 1(PD-L1),human epidermal growth factor receptor 2(HER2),and nectin cell adhesion molecule 4(Nectin 4).How to screen patients suitable for these treatments and monitor the therapy?Nuclear medicine with specific radiopharmaceuticals can visualize the expression level of those targets in systemic lesions and evaluate the efficacy of treatment.In addition to radiopharmaceuticals,imaging equipment is also a key step for nuclear medicine.Advanced equipment including total-body positron emission tomography/computed tomography(PET/CT)and positron emission tomography/magnetic resonance imaging(PET/MRI)has been developed,which contribute to the diagnosis and treatment of tumors,as well as the development of new radiopharmaceuticals.Here,we conclude most recently advances of radiopharmaceuticals in nuclear medicine,and they substantially increase the“arsenal”of clinicians for tumor therapy.展开更多
Various single or multi-modality therapeutic options are available to treat pain of bone metastasis in patients with prostate cancer.Different radionuclides that emitβ-rays such as 153Samarium and 89Strontium and ach...Various single or multi-modality therapeutic options are available to treat pain of bone metastasis in patients with prostate cancer.Different radionuclides that emitβ-rays such as 153Samarium and 89Strontium and achieve palliation are commercially available.In contrast toβ-emitters,223Radium as a a-emitter has a short path-length.The advantage of the a-emitter is thus a highly localized biological effect that is caused by radiation induced DNA double-strand breaks and subsequent cell killing and/or limited effectiveness of cellular repair mechanisms.Due to the limited range of the a-particles the bone surface to red bone marrow dose ratio is also lower for 223Radium which is expressed in a lower myelotoxicity.The a emitter 223Radium dichloride is the first radiopharmaceutical that significantly prolongslife in castrate resistant prostate cancer patients with wide-spread bone metastatic disease.In a phaseⅢ,randomized,double-blind,placebo-controlled study 921patients with castration-resistant prostate cancer and bone metastases were randomly assigned.The analysis confirmed the 223Radium survival benefit compared to the placebo(median,14.9 mo vs 11.3 mo;P<0.001).In addition,the treatment results in pain palliation and thus,improved quality of life and a delay of skeletal related events.At the same time the toxicity profile of223Radium was favourable.Since May 2013,223Radium dichloride(Xofigo?)is approved by the US Food and Drug Administration.展开更多
Natural products provide a bountiful supply of pharmacologically relevant precursors for the development of various drug-related molecules,including radiopharmaceuticals.However,current knowledge regarding the importa...Natural products provide a bountiful supply of pharmacologically relevant precursors for the development of various drug-related molecules,including radiopharmaceuticals.However,current knowledge regarding the importance of natural products in developing new radiopharmaceuticals remains limited.To date,several radionuclides,including gallium-68,technetium-99m,fluorine-18,iodine-131,and iodine-125,have been extensively studied for the synthesis of diagnostic and therapeutic radiopharmaceuticals.The availability of various radiolabeling methods allows the incorporation of these radionuclides into bioactive molecules in a practical and efficient manner.Of the radiolabeling methods,direct radioiodination,radiometal complexation,and halogenation are generally suitable for natural products owing to their simplicity and robustness.This review highlights the pharmacological benefits of curcumin and its analogs,flavonoids,and marine peptides in treating human pathologies and provides a perspective on the potential use of these bioactive compounds as molecular templates for the design and development of new radiopharmaceuticals.Additionally,this review provides insights into the current strategies for labeling natural products with various radionuclides using either direct or indirect methods.展开更多
To improve the relevant methods of the quality control standards of tumor Positron Emission Computed Tomography(PET)radiopharmaceuticals and to reduce the clinical application risks of such drugs,this article compares...To improve the relevant methods of the quality control standards of tumor Positron Emission Computed Tomography(PET)radiopharmaceuticals and to reduce the clinical application risks of such drugs,this article compares and analyzes the similarities and differences of the quality control standards of tumor PET radiopharmaceuticals in the Pharmacopoeia of People’s Republic of China(ChP2020),European Pharmacopoeia(EP8.0)and United States Pharmacopoeia(USP39),focusing on comparing and analyzing the identification(identification method),inspection(pH,residual solvent,bacterial endotoxin,sterility,and impurities),and content determination(radionuclear purity,radiochemical purity,and radioactive concentration)of tumor PET radiopharmaceuticals.The quality control standards of ChP2020 for tumor PET radiopharmaceuticals are relatively equivalent to the quality control standards of USP39 but are not as stringent as those of EP8.0.In general,EP8.0 has the most comprehensive and strict quality control standards for tumor PET radiopharmaceuticals.The quality control standards of tumor PET radiopharmaceuticals in the Chinese Pharmacopoeia can be improved by referring to international standards,especially the European Pharmacopoeia.展开更多
The metaiodobenzylguanidine (MIBG) radiopharmaceutical, an analogue of norepinephrine, has been used to diagnose certain diseases in the cardiovascular system when radiolabeled with 123I. This radiopharmaceutical can ...The metaiodobenzylguanidine (MIBG) radiopharmaceutical, an analogue of norepinephrine, has been used to diagnose certain diseases in the cardiovascular system when radiolabeled with 123I. This radiopharmaceutical can also be used to treat tumors, such as neuroblastomas and pheochromocytomas, when radiolabeled with 131I. Its clinical use is often accompanied by a slow intravenous administration, where a significant dose of radiation can directly affect workers in nuclear medicine services. To overcome this problem, the incorporation and controlled release of radiopharmaceuticals from the matrix of mesoporous systems based on silica, such as SBA-15 and hybrid [SBA-15/P(N-iPAAm)], can lead to a significant reduction in radiation doses received by workers. In the present study, silica matrices SBA-15 and hybrid [SBA-15/P(N-iPAAm)] containing the radiopharmaceutical MIBG were prepared and physicochemically characterized through FTIR, SEM, and small angle X-ray diffraction techniques. The release profiles of MIBG from SBA-15 and [SBA-15/P(N-iPAAm)] were studied in a simulated body fluid (SBF) to evaluate their potential application as vehicles for controlled releases. Furthermore, in vitro studies were performed to assess the cytotoxicity of matrices as compared to human lung fibroblast cells (MRC-5). The results revealed that the amount of MIBG incorporated within the studied matrices was indeed quite different, showing that only the hybrid [SBA-15/P(N-iPAAm)] system allowed for a more adequate release profile of MIGB. Taking all results into consideration, it can be concluded that the hybrid matrix [SBA-15/P(N-iPAAm)] can be considered a potential alternative material for the controlled release delivery of radio-pharmaceuticals.展开更多
Radiopharmaceuticals involve the local delivery of radionuclides to targeted lesions for the diagnosis and treatment of multiple diseases.Radiopharmaceutical therapy,which directly causes systematic and irreparable da...Radiopharmaceuticals involve the local delivery of radionuclides to targeted lesions for the diagnosis and treatment of multiple diseases.Radiopharmaceutical therapy,which directly causes systematic and irreparable damage to targeted cells,has attracted increasing attention in the treatment of refractory diseases that are not sensitive to current therapies.As the Food and Drug Administration(FDA)approvals of[177Lu]Lu-DOTA-TATE,[177Lu]Lu-PSMA-617 and their complementary diagnostic agents,namely,[68Ga]Ga-DOTA-TATE and[68Ga]Ga-PSMA-11,targeted radiopharmaceutical-based theranostics(radiotheranostics)are being increasingly implemented in clinical practice in oncology,which lead to a new era of radiopharmaceuticals.The new generation of radiopharmaceuticals utilizes a targeting vector to achieve the accurate delivery of radionuclides to lesions and avoid off-target deposition,making it possible to improve the efficiency and biosafety of tumour diagnosis and therapy.Numerous studies have focused on developing novel radiopharmaceuticals targeting a broader range of disease targets,demonstrating remarkable in vivo performance.These include high tumor uptake,prolonged retention time,and favorable pharmacokinetic properties that align with clinical standards.While radiotheranostics have been widely applied in tumor diagnosis and therapy,their applications are now expanding to neurodegenerative diseases,cardiovascular diseases,and inflammation.Furthermore,radiotheranostic-empowered precision medicine is revolutionizing the cancer treatment paradigm.Diagnostic radiopharmaceuticals play a pivotal role in patient stratification and treatment planning,leading to improved therapeutic outcomes in targeted radionuclide therapy.This review offers a comprehensive overview of the evolution of radiopharmaceuticals,including both FDA-approved and clinically investigated agents,and explores the mechanisms of cell death induced by radiopharmaceuticals.It emphasizes the significance and future prospects of theranostic-based radiopharmaceuticals in advancing precision medicine.展开更多
The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth,migration,and treatment response,thereby influencing tumor progression and therapeutic outcomes.Owing to the prolifer...The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth,migration,and treatment response,thereby influencing tumor progression and therapeutic outcomes.Owing to the proliferation and metastasis of tumors,fibroblast activation protein(FAP)is typically highly expressed in the tumor stroma,whereas it is nearly absent in adult normal tissues and benign lesions,making it an attractive target for precision medicine.Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy.This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization.Within its scope,this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs,combined with insights from structure-activity relationships and clinical studies,providing a valuable perspective for radiopharmaceutical clinical development and application.展开更多
Tumor-targeted radiopharmaceuticals have become an attractive modality for tumor diagnosis and treatment in clinics.However;their wide clinical applications are seriously impeded by poor tumor targeting;rapid systemic...Tumor-targeted radiopharmaceuticals have become an attractive modality for tumor diagnosis and treatment in clinics.However;their wide clinical applications are seriously impeded by poor tumor targeting;rapid systemic clearance;and short tumor retention.Therefore;developing advanced radiopharmaceuticals with great tumor specificity and prolonged retention time is highly desirable for efficient tumor treatment.Herein;we report a tumor-targeted covalently anchoring strategy that selectively crosslinks the radiopharmaceuticals to intratumoral macromolecules for prolonged tumor theranostics.A covalent multi-targeted radiopharmaceutical(CMTR)d-IR-2(^(125)IRGD)that includes a sulfenic acid-reactive 1,3-cyclohexanedione group was developed.We demonstrated this probe could specifically accumulate at the tumor site and bind to the sulfenated proteins that are overexpressed within tumors;which greatly prevents the efflux of probes in tumor tissues while having faster clearance in healthy tissues resulting in 12 h longer tumor retention than conventional probes for sensitive NIR and SPECT/CT detection of tumors in vivo.More notably;the ^(131)I-labeled probe could significantly suppress the growth of lung tumor A549.We thus envision that this work may offer a promising approach to developing effective radiopharmaceuticals for precise diagnosis and treatment of various tumors.展开更多
Chemotherapy is the first-line treatment for cancer, but its systemic toxicity can be severe. Tumorselective prodrug activation offers promising opportunities to reduce systemic toxicity. Here, we present a strategy f...Chemotherapy is the first-line treatment for cancer, but its systemic toxicity can be severe. Tumorselective prodrug activation offers promising opportunities to reduce systemic toxicity. Here, we present a strategy for activating prodrugs using radiopharmaceuticals. This strategy enables the targeted release of chemotherapeutic agents due to the high tumor-targeting capability of radiopharmaceuticals. [^(18)F]FDG(2-[^(18)F]-fluoro-2-deoxy-D-glucose), one of the most widely used radiopharmaceuticals in clinics, can trigger Pt(IV) complex for controlled release of axial ligands in tumors, it might be mediated by hydrated electrons generated by water radiolysis resulting from the decay of radionuclide18F. Its application offers the controlled release of fluorogenic probes and prodrugs in living cells and tumor-bearing mice. Of note,an OxaliPt(IV) linker is designed to construct an [^(18)F]FDG-activated antibody-drug conjugate(Pt-ADC).Sequential injection of Pt-ADC and [^(18)F]FDG efficiently releases the toxin in the tumor and remarkably suppresses the tumor growth. Radiotherapy is booming as a perturbing tool for prodrug activation,and we find that [^(18)F]FDG is capable of deprotecting various radiotherapy-removable protecting groups(RPGs). Our results suggest that tumor-selective radiopharmaceutical may function as a trigger, for developing innovative prodrug activation strategies with enhanced tumor selectivity.展开更多
Radiopharmaceuticals have become indispensable tools in precision medicine,revolutionizing diagnostic imaging and targeted therapeutic strategies.This manuscript provides an overview of advancements globally and in Ch...Radiopharmaceuticals have become indispensable tools in precision medicine,revolutionizing diagnostic imaging and targeted therapeutic strategies.This manuscript provides an overview of advancements globally and in China,focusing on the classification and clinical applications of radiopharmaceuticals,particularly in oncology and neurology.Recent progress includes PET/SPECT diagnostic agents and therapeutic radionuclides that provide precise treatment while limiting damage to healthy tissues.Emerging technologies,such as artificial intelligence,novel ligands,advanced radionuclides,and combination therapies,present promising avenues to further enhance the efficacy and accessibility of the field.Despite these achievements,challenges remain in production,regulatory,and costs,underscoring the need for ongoing innovation and international collaboration to fully realize the potential of radiopharmaceuticals in personalized healthcare and optimize patient outcomes.展开更多
Biliary tract cancer(BTC)is a group of heterogeneous sporadic diseases,including intrahepatic,hilar,and distal cholangiocarcinoma,as well as gallbladder cancer.BTC is characterized by high invasiveness and extremely p...Biliary tract cancer(BTC)is a group of heterogeneous sporadic diseases,including intrahepatic,hilar,and distal cholangiocarcinoma,as well as gallbladder cancer.BTC is characterized by high invasiveness and extremely poor prognosis,with a global increased incidence due to intrahepatic cholangiocarcinoma(ICC).The 18Ffludeoxyglucose positron emission tomography(PET)computed tomography(18F-FDG PET/CT)combines glucose metabolic information(reflecting the glycolytic activity of tumor cells)with anatomical structure to assess tumor metabolic heterogeneity,systemic metastasis,and molecular characteristics noninvasively,overcoming the limitations of traditional imaging in the detection of micrometastases and recurrent lesions.18F-FDG PET/CT offers critical insights in clinical staging,therapeutic evaluation,and prognostic prediction of BTC.This article reviews research progress in this field over the past decade,with a particular focus on the advances made in the last 3 years,which have not been adequately summarized and recognized.The research paradigm in this field is shifting from qualitative to quantitative studies,and there have been significant breakthroughs in using 18F-FDG PET/CT metabolic information to predict gene expression in ICC.Radiomics and deep learning techniques have been applied to ICC for prognostic prediction and differential diagnosis.Additionally,PET/magnetic resonance imaging is increasingly demonstrating its value in this field.展开更多
Soft tissue sarcomas(STS)are rare malignant tumors originating from mesoder-mal tissues with a poor prognosis,accounting for approximately 1%of all malig-nancies and comprising around 50 distinct subtypes.Conventional...Soft tissue sarcomas(STS)are rare malignant tumors originating from mesoder-mal tissues with a poor prognosis,accounting for approximately 1%of all malig-nancies and comprising around 50 distinct subtypes.Conventional imaging mo-dalities,such as computed tomography(CT)and magnetic resonance imaging(MRI),primarily provide anatomical information,whereas 18F-fluorodeoxyglucose positron emission tomography/CT(18F-FDG PET/CT)integrates functional metabolic and anatomical imaging,serving as a critical complementary tool in the diagnosis and management of STS.This article reviews recent advances in the application of 18F-FDG PET/CT for STS.The advantages of 18F-FDG PET/CT in STS include:(1)Early detection of metabolic activity changes in tumors,partic-ularly when morphological alterations are insignificant;(2)Effective differen-tiation between benign and malignant soft tissue tumors,as well as aiding in distinguishing high-grade from low-grade sarcomas;(3)Identification of occult metastatic lesions,improving staging accuracy,and facilitating restaging in cases of recurrence or metastasis;(4)Utilization of parameters such as maximum stan-dardized uptake value and metabolic tumor volume to assist in tumor grading and prognostic evaluation;and(5)Monitoring treatment response to guide adjust-ments in personalized therapeutic strategies.However,18F-FDG PET/CT has limitations in diagnosis of certain STS subtypes(e.g.,myxoid liposarcoma),detection and biopsy of metastatic lymph nodes,necessitating integration with clinical evaluation and other imaging techniques.18F-FDG PET/CT is poised to play an increasingly vital role in the precision diagnosis and treatment of STS.展开更多
Polyamine metabolism dysregulation is a hallmark of many cancers,offering a promising avenue for early tumor theranostics.This study presents the development of a nuclear probe derived from spermidine(SPM)for dual-pur...Polyamine metabolism dysregulation is a hallmark of many cancers,offering a promising avenue for early tumor theranostics.This study presents the development of a nuclear probe derived from spermidine(SPM)for dual-purpose tumor PET imaging and internal radiation therapy.The probe,radiolabeled with either[68Ga]Ga for diagnostic applications or[177Lu]Lu for therapeutic use,was synthesized with exceptional purity,stability,and specific activity.Extensive testing involving 12 different tumor cell lines revealed remarkable specificity towards B16 melanoma cells,showcasing outstanding tumor localization and target-to-non-target ratio.Mechanistic investigations employing polyamines,non-labeled precursor,and polyamine transport system(PTS)inhibitor,consistently affirmed the probe?s targetability through recognition of the PTS.Notably,while previous reports indicated PTS upregulation in various tumor types for targeted therapy,this study observed no positive signals,highlighting a concentration-dependent discrepancy between targeting for therapy and diagnosis.Furthermore,when labeled with[177Lu],the probe demonstrated its therapeutic potential by effectively controlling tumor growth and extending mouse survival.Investigations into biodistribution,excretion,and biosafety in healthy humans laid a robust foundation for clinical translation.This study introduces a versatile SPM-based nuclear probe with applications in precise tumor theranostics,offering promising prospects for clinical implementation.展开更多
Density functional theory method has been employed to investigate the structures of the prototypical technetium-labeled diphosphonate complex 99mTc-MDP, where MDP represents methylenediphosphonic acid. A total of 14 t...Density functional theory method has been employed to investigate the structures of the prototypical technetium-labeled diphosphonate complex 99mTc-MDP, where MDP represents methylenediphosphonic acid. A total of 14 trial structures were generated by allowing for the geometric, conformational, charge, and spin isomerism. Based on the optimized structures and calculated energies at the B3LYP/LANL2DZ level, two stable isomers were determined for the title complex. And they were further studied systematically in comparison with the experimental structure. The basis sets 6-31G＊（LANL2DZ for Tc）, 6-31G＊（cc-pVDZ-pp for Tc）, and DGDZVP have also been employed in combination with the B3LYP functional to study the basis set effect on the geometries of isomers. The optimized structures agree well with the available experimental data, and the bond lengths are more sensitive to the basis set than the bond angles. The charge distributions were studied by the Mulliken population analysis and natural bond orbital analysis. The results reflect a significant ligand-to-metal electron donation.展开更多
基金the National Key R&D Program of China(No.2023YFE0197700)the Fundamental Research Funds for the Central Universities(No.2632023TD04).
文摘Radiopharmaceuticals operate by combining radionuclides with carriers.The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues.In comparison to external beam radiation therapy,radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity.This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment.Several key radionuclides are examined,including^(223)Ra,^(90)Y,Lutetium-177(^(177)Lu),212 Pb,and Actinium-225(^(225)Ac).It also explores the current development trends of radiopharmaceuticals,encompassing the introduction of novel radionuclides,advancements in imaging technologies,integrated diagnosis and treatment approaches,and equipment-medication combinations.We review the progress in the development of new treatments,such as neutron capture therapy,proton therapy,and heavy ion therapy.Furthermore,we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.
基金Capital's Funds for Health Improvement and Research,Grant/Award Numbers:2022‐2Z‐2154,2022‐2Z‐2155Youth talent support program,Grant/Award Number:A002863。
文摘1|INTRODUCTION Cancer has emerged as a significant threat to human life,and its incidence and mortality are increasing rapidly.As clinicians increasingly seek to noninvasively investigate tumor phenotypes and evaluate functional and molecular responses to therapy,the combination of diagnostic im-aging with targeted therapy is becoming more widely implemented[1].Targeted radionuclide therapy involves the use of small molecules,peptides,and/or antibodies as carriers for therapeutic radionuclides,with these being referred to as radiopharmaceuticals.Radiopharmaceuti-cals,also known as molecular probes in nuclear medicine,play a vital role in clinical diagnosis and therapy.Currently,there are numerous radiopharmaceuticals approved or under research worldwide for a wide range of indications.At the end of March 2022,there were 60 radiopharmaceuticals approved for marketing by the Food and Drug Administration(FDA)[2](Supplemental Table)[2].As of October 2023,42 radiopharmaceuticals have been approved for marketing by the National Medical Products Administration(NMPA)[3].However,there remains an urgent need to identify new targets and new drug molecules to advance the process of radiopharma-ceutical research and development.
基金the financial supports from the National Natural Science Foundation of China(No.22006105)the China Postdoctoral Science Foundation(No.2020M683309)the Fundamental Research Funds for the Central Universities。
文摘Astatine-211(^(211)At,t_(1/2)=7.21 h)emitting twoαparticles with energies of 5.87 and 7.45 MeV,can lead to a high linear energy transfer(LET=98.84 ke V/μm)and short tissue range(50~90μm).Since the 1950s,^(211)At had stepped into endoradiotherapy and has always been regarded as one of the most promisingα-emitters for targeted-alpha therapy(TAT)in various malignancies.In the past two decades,^(211)At related radiopharmaceuticals have achieved great progress in the studies of basic physicochemical properties of astatine,^(211)At labeling strategies,preclinical and clinical studies,producing profound effects in nuclear medicine.This work will give a panorama of^(211)At-related researches in the recent 20 years,which will cover both the fundamental insights of^(211)At radiochemistry and applied labeling compounds.It can provide some important hints for the studies of TAT and other radiopharmaceuticals applied in tumor radiotherapy.
文摘Samarium-153- EDTMP (ethylene diamine tetramethylene phosphonate), for its promising biological properties, has been proved as a palliating therapeutic agent for bone tumor in human beings. 153Sin with high radionuclear purity and specific activity of 5.18 GBq (140 mCi)/mg Sm2O3 was prepared by irradiating naturalSm2O3(152Sm, 26.7%) sample, replacing costly enriched samarium oxide target, at a flux of 4x 1013n.cm-2.s-1 for 110 h. The yield of 153Sm complexing with EDTMP is greater than 98% at PH 8￣10 in boiling water bath for 30 min, and not significantly decreases within one week after 153Sm-EDTMP complex formation.
文摘Genetic heterogeneity and chemotherapy-resistant ＇stem cells＇ represent two of the most pressing issues in devising new strategies for the treatment of advanced prostate cancer. Though curative strategies have long been present for men with localized disease, metastatic prostate cancer is currently incurable. Though substantial improvements in outcomes are now possible through the utilization of newly approved therapies, novel combinations are clearly needed. Herein we describe potentially synergistic interactions between bone stromal-targeted radiopharmaceuticals and other therapies for treatment of bone-metastatic prostate cancer. Radiation has long been known to synergize with cytotoxic chemotherapies and recent data also suggest the possibility of synergy when combining radiation and immune-based strategies. Combination therapies will be required to substantially improve survival for men with castrate-resistant metastatic prostate cancer and we hypothesize that bone-targeted radiopharmaceuticals will play an important role in this Drocess.
基金Supported by National Natural Science Foundation,Nos.81171399,51473071,81101077,21401084,81401450 and 81472749Jiangsu Province Foundation,Nos.BE2014609,BE2012622,BL2012031 and BM2012066Wuxi Foundation,No.CSZ0N1320
文摘Pancreatic cancer(PC) is a major health problem. Conventional imaging modalities show limited accuracy for reliable assessment of the tumor. Recent researches suggest that molecular imaging techniques with tracers provide more biologically relevant information and are benefit for the diagnosis of the cancer. In addition,radiopharmaceuticals also play more important roles in treatment of the disease. This review summaries the advancement of the radiolabeled compounds in the theranostics of PC.
文摘Nuclear medicine plays an irreplaceable role in the diagnosis and treatment of tumors.Radiopharmaceuticals are important components of nuclear medicine.Among the radiopharmaceuticals approved by the Food and Drug Administration(FDA),radio-tracers targeting prostate-specific membrane antigen(PSMA)and somatostatin receptor(SSTR)have held essential positions in the diagnosis and treatment of prostate cancers and neuroendocrine neoplasms,respectively.In recent years,FDA-approved serials of immune-therapy and targeted therapy drugs targeting programmed death 1(PD-1)/programmed death ligand 1(PD-L1),human epidermal growth factor receptor 2(HER2),and nectin cell adhesion molecule 4(Nectin 4).How to screen patients suitable for these treatments and monitor the therapy?Nuclear medicine with specific radiopharmaceuticals can visualize the expression level of those targets in systemic lesions and evaluate the efficacy of treatment.In addition to radiopharmaceuticals,imaging equipment is also a key step for nuclear medicine.Advanced equipment including total-body positron emission tomography/computed tomography(PET/CT)and positron emission tomography/magnetic resonance imaging(PET/MRI)has been developed,which contribute to the diagnosis and treatment of tumors,as well as the development of new radiopharmaceuticals.Here,we conclude most recently advances of radiopharmaceuticals in nuclear medicine,and they substantially increase the“arsenal”of clinicians for tumor therapy.
文摘Various single or multi-modality therapeutic options are available to treat pain of bone metastasis in patients with prostate cancer.Different radionuclides that emitβ-rays such as 153Samarium and 89Strontium and achieve palliation are commercially available.In contrast toβ-emitters,223Radium as a a-emitter has a short path-length.The advantage of the a-emitter is thus a highly localized biological effect that is caused by radiation induced DNA double-strand breaks and subsequent cell killing and/or limited effectiveness of cellular repair mechanisms.Due to the limited range of the a-particles the bone surface to red bone marrow dose ratio is also lower for 223Radium which is expressed in a lower myelotoxicity.The a emitter 223Radium dichloride is the first radiopharmaceutical that significantly prolongslife in castrate resistant prostate cancer patients with wide-spread bone metastatic disease.In a phaseⅢ,randomized,double-blind,placebo-controlled study 921patients with castration-resistant prostate cancer and bone metastases were randomly assigned.The analysis confirmed the 223Radium survival benefit compared to the placebo(median,14.9 mo vs 11.3 mo;P<0.001).In addition,the treatment results in pain palliation and thus,improved quality of life and a delay of skeletal related events.At the same time the toxicity profile of223Radium was favourable.Since May 2013,223Radium dichloride(Xofigo?)is approved by the US Food and Drug Administration.
文摘Natural products provide a bountiful supply of pharmacologically relevant precursors for the development of various drug-related molecules,including radiopharmaceuticals.However,current knowledge regarding the importance of natural products in developing new radiopharmaceuticals remains limited.To date,several radionuclides,including gallium-68,technetium-99m,fluorine-18,iodine-131,and iodine-125,have been extensively studied for the synthesis of diagnostic and therapeutic radiopharmaceuticals.The availability of various radiolabeling methods allows the incorporation of these radionuclides into bioactive molecules in a practical and efficient manner.Of the radiolabeling methods,direct radioiodination,radiometal complexation,and halogenation are generally suitable for natural products owing to their simplicity and robustness.This review highlights the pharmacological benefits of curcumin and its analogs,flavonoids,and marine peptides in treating human pathologies and provides a perspective on the potential use of these bioactive compounds as molecular templates for the design and development of new radiopharmaceuticals.Additionally,this review provides insights into the current strategies for labeling natural products with various radionuclides using either direct or indirect methods.
基金National Key Research and Development Plan(Grant No.2017YFC0113305).
文摘To improve the relevant methods of the quality control standards of tumor Positron Emission Computed Tomography(PET)radiopharmaceuticals and to reduce the clinical application risks of such drugs,this article compares and analyzes the similarities and differences of the quality control standards of tumor PET radiopharmaceuticals in the Pharmacopoeia of People’s Republic of China(ChP2020),European Pharmacopoeia(EP8.0)and United States Pharmacopoeia(USP39),focusing on comparing and analyzing the identification(identification method),inspection(pH,residual solvent,bacterial endotoxin,sterility,and impurities),and content determination(radionuclear purity,radiochemical purity,and radioactive concentration)of tumor PET radiopharmaceuticals.The quality control standards of ChP2020 for tumor PET radiopharmaceuticals are relatively equivalent to the quality control standards of USP39 but are not as stringent as those of EP8.0.In general,EP8.0 has the most comprehensive and strict quality control standards for tumor PET radiopharmaceuticals.The quality control standards of tumor PET radiopharmaceuticals in the Chinese Pharmacopoeia can be improved by referring to international standards,especially the European Pharmacopoeia.
基金This research was supported by the Brazilian agencies CAPES,CNPq,and FAPEMIGThe authors would like to thank the Microscopy Center at UFMG for its techni-cal support during electron microscopy work.
文摘The metaiodobenzylguanidine (MIBG) radiopharmaceutical, an analogue of norepinephrine, has been used to diagnose certain diseases in the cardiovascular system when radiolabeled with 123I. This radiopharmaceutical can also be used to treat tumors, such as neuroblastomas and pheochromocytomas, when radiolabeled with 131I. Its clinical use is often accompanied by a slow intravenous administration, where a significant dose of radiation can directly affect workers in nuclear medicine services. To overcome this problem, the incorporation and controlled release of radiopharmaceuticals from the matrix of mesoporous systems based on silica, such as SBA-15 and hybrid [SBA-15/P(N-iPAAm)], can lead to a significant reduction in radiation doses received by workers. In the present study, silica matrices SBA-15 and hybrid [SBA-15/P(N-iPAAm)] containing the radiopharmaceutical MIBG were prepared and physicochemically characterized through FTIR, SEM, and small angle X-ray diffraction techniques. The release profiles of MIBG from SBA-15 and [SBA-15/P(N-iPAAm)] were studied in a simulated body fluid (SBF) to evaluate their potential application as vehicles for controlled releases. Furthermore, in vitro studies were performed to assess the cytotoxicity of matrices as compared to human lung fibroblast cells (MRC-5). The results revealed that the amount of MIBG incorporated within the studied matrices was indeed quite different, showing that only the hybrid [SBA-15/P(N-iPAAm)] system allowed for a more adequate release profile of MIGB. Taking all results into consideration, it can be concluded that the hybrid matrix [SBA-15/P(N-iPAAm)] can be considered a potential alternative material for the controlled release delivery of radio-pharmaceuticals.
基金supported by the National Natural Science Foundation of China(No.82372002)the Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences(No.2022-RC350-04)+5 种基金the CAMS Innovation Fund for Medical Sciences(Nos.2023-I2M-2-006,2023-I2M-QJ-010,02149942,2021-I2M-1-026,2022-I2M-2-002-2,and 2021-I2M-3-001)the National Key Research and Development Programme of China(No.2022YFE0111700)the Beijing Nova Programme to K.H..This work was also supported by the Beijing Natural Science Foundation(Nos.L234044 and L248087)the Fundamental Research Funds for the Central Universities(Nos.3332023044 and 3332023151)the CIRP Open Fund of Radiation Protection Laboratories(No.ZHYLYB2021005)the China National Nuclear Corporation Young Talent Programme.
文摘Radiopharmaceuticals involve the local delivery of radionuclides to targeted lesions for the diagnosis and treatment of multiple diseases.Radiopharmaceutical therapy,which directly causes systematic and irreparable damage to targeted cells,has attracted increasing attention in the treatment of refractory diseases that are not sensitive to current therapies.As the Food and Drug Administration(FDA)approvals of[177Lu]Lu-DOTA-TATE,[177Lu]Lu-PSMA-617 and their complementary diagnostic agents,namely,[68Ga]Ga-DOTA-TATE and[68Ga]Ga-PSMA-11,targeted radiopharmaceutical-based theranostics(radiotheranostics)are being increasingly implemented in clinical practice in oncology,which lead to a new era of radiopharmaceuticals.The new generation of radiopharmaceuticals utilizes a targeting vector to achieve the accurate delivery of radionuclides to lesions and avoid off-target deposition,making it possible to improve the efficiency and biosafety of tumour diagnosis and therapy.Numerous studies have focused on developing novel radiopharmaceuticals targeting a broader range of disease targets,demonstrating remarkable in vivo performance.These include high tumor uptake,prolonged retention time,and favorable pharmacokinetic properties that align with clinical standards.While radiotheranostics have been widely applied in tumor diagnosis and therapy,their applications are now expanding to neurodegenerative diseases,cardiovascular diseases,and inflammation.Furthermore,radiotheranostic-empowered precision medicine is revolutionizing the cancer treatment paradigm.Diagnostic radiopharmaceuticals play a pivotal role in patient stratification and treatment planning,leading to improved therapeutic outcomes in targeted radionuclide therapy.This review offers a comprehensive overview of the evolution of radiopharmaceuticals,including both FDA-approved and clinically investigated agents,and explores the mechanisms of cell death induced by radiopharmaceuticals.It emphasizes the significance and future prospects of theranostic-based radiopharmaceuticals in advancing precision medicine.
基金supported by the National Natural Science Foundation of China(No.82372002)the Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences(No.2022-RC350-04)+6 种基金the CAMS Innovation Fund for Medical Sciences(Nos.2024-12M-ZH-009,2023-I2M-2-006,2023-I2M-QJ010,2021-I2M-1-026,and 2021-I2M-3-001,China)the Beijing Nova Program and Beijing Nova Program Interdisciplinary Cooperation Project to Ksupported by the Beijing Natural Science Foundation(Nos.L234044,L248087,L246051 and 7252206,China)the Fundamental Research Funds for the Central Universities(Nos.3332023044,3332023151,China)the China Postdoctoral Science Foundation(No.2025M773592)the China National Nuclear Corporation Young Talent Program,the special project of“Technological Innovation”project of CNNC Medical Industry Co.Ltd(ZHYLYB2021005)Medical+X Innovation Team of the Discipline Construction Enhancement Project,the Second Affiliated Hospital of Soochow University(XKTJ-TD202410).
文摘The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth,migration,and treatment response,thereby influencing tumor progression and therapeutic outcomes.Owing to the proliferation and metastasis of tumors,fibroblast activation protein(FAP)is typically highly expressed in the tumor stroma,whereas it is nearly absent in adult normal tissues and benign lesions,making it an attractive target for precision medicine.Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy.This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization.Within its scope,this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs,combined with insights from structure-activity relationships and clinical studies,providing a valuable perspective for radiopharmaceutical clinical development and application.
基金supported by the National Natural Science Foundation of China(T2325019,22077092)the Basic Research Program of Jiangsu(BK20243030)+3 种基金the Special Project of“Technological Innovation”Project of CNNC Medical Industry Co.Ltd.(ZHYLYB2021001)the Four“Batches”Innovation Project of Invigorating Medical through Science and Technology of Shanxi Province(2022XM19)the Open Project Program of the State Key Laboratory of Radiation Medicine and Protection(GZK12024016,GZK12023050,GZK12024013)a Project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Tumor-targeted radiopharmaceuticals have become an attractive modality for tumor diagnosis and treatment in clinics.However;their wide clinical applications are seriously impeded by poor tumor targeting;rapid systemic clearance;and short tumor retention.Therefore;developing advanced radiopharmaceuticals with great tumor specificity and prolonged retention time is highly desirable for efficient tumor treatment.Herein;we report a tumor-targeted covalently anchoring strategy that selectively crosslinks the radiopharmaceuticals to intratumoral macromolecules for prolonged tumor theranostics.A covalent multi-targeted radiopharmaceutical(CMTR)d-IR-2(^(125)IRGD)that includes a sulfenic acid-reactive 1,3-cyclohexanedione group was developed.We demonstrated this probe could specifically accumulate at the tumor site and bind to the sulfenated proteins that are overexpressed within tumors;which greatly prevents the efflux of probes in tumor tissues while having faster clearance in healthy tissues resulting in 12 h longer tumor retention than conventional probes for sensitive NIR and SPECT/CT detection of tumors in vivo.More notably;the ^(131)I-labeled probe could significantly suppress the growth of lung tumor A549.We thus envision that this work may offer a promising approach to developing effective radiopharmaceuticals for precise diagnosis and treatment of various tumors.
基金was Beijing Municipal Natural Science Foundation (Z200018)National Natural Science Foundation of China (22225603)+2 种基金Ministry of Science and Technology of the People’s Republic of China (2021YFA1601400)Program of the Local Science and Technology Development (Gansu Province) Guided by Central Government (YDZX20216200001201)Changping Laboratory, and the Central Guidance for Local Science and Technology Development Projects (202138-03)。
文摘Chemotherapy is the first-line treatment for cancer, but its systemic toxicity can be severe. Tumorselective prodrug activation offers promising opportunities to reduce systemic toxicity. Here, we present a strategy for activating prodrugs using radiopharmaceuticals. This strategy enables the targeted release of chemotherapeutic agents due to the high tumor-targeting capability of radiopharmaceuticals. [^(18)F]FDG(2-[^(18)F]-fluoro-2-deoxy-D-glucose), one of the most widely used radiopharmaceuticals in clinics, can trigger Pt(IV) complex for controlled release of axial ligands in tumors, it might be mediated by hydrated electrons generated by water radiolysis resulting from the decay of radionuclide18F. Its application offers the controlled release of fluorogenic probes and prodrugs in living cells and tumor-bearing mice. Of note,an OxaliPt(IV) linker is designed to construct an [^(18)F]FDG-activated antibody-drug conjugate(Pt-ADC).Sequential injection of Pt-ADC and [^(18)F]FDG efficiently releases the toxin in the tumor and remarkably suppresses the tumor growth. Radiotherapy is booming as a perturbing tool for prodrug activation,and we find that [^(18)F]FDG is capable of deprotecting various radiotherapy-removable protecting groups(RPGs). Our results suggest that tumor-selective radiopharmaceutical may function as a trigger, for developing innovative prodrug activation strategies with enhanced tumor selectivity.
基金supported by the construction project of Shanghai Key Laboratory of Molecular Imaging of China(No.18DZ2260400)the research grants from the National Natural Science Foundation of China(No.82127807)the National Key Research and Development Program of China(No.2020YFA0909000).
文摘Radiopharmaceuticals have become indispensable tools in precision medicine,revolutionizing diagnostic imaging and targeted therapeutic strategies.This manuscript provides an overview of advancements globally and in China,focusing on the classification and clinical applications of radiopharmaceuticals,particularly in oncology and neurology.Recent progress includes PET/SPECT diagnostic agents and therapeutic radionuclides that provide precise treatment while limiting damage to healthy tissues.Emerging technologies,such as artificial intelligence,novel ligands,advanced radionuclides,and combination therapies,present promising avenues to further enhance the efficacy and accessibility of the field.Despite these achievements,challenges remain in production,regulatory,and costs,underscoring the need for ongoing innovation and international collaboration to fully realize the potential of radiopharmaceuticals in personalized healthcare and optimize patient outcomes.
文摘Biliary tract cancer(BTC)is a group of heterogeneous sporadic diseases,including intrahepatic,hilar,and distal cholangiocarcinoma,as well as gallbladder cancer.BTC is characterized by high invasiveness and extremely poor prognosis,with a global increased incidence due to intrahepatic cholangiocarcinoma(ICC).The 18Ffludeoxyglucose positron emission tomography(PET)computed tomography(18F-FDG PET/CT)combines glucose metabolic information(reflecting the glycolytic activity of tumor cells)with anatomical structure to assess tumor metabolic heterogeneity,systemic metastasis,and molecular characteristics noninvasively,overcoming the limitations of traditional imaging in the detection of micrometastases and recurrent lesions.18F-FDG PET/CT offers critical insights in clinical staging,therapeutic evaluation,and prognostic prediction of BTC.This article reviews research progress in this field over the past decade,with a particular focus on the advances made in the last 3 years,which have not been adequately summarized and recognized.The research paradigm in this field is shifting from qualitative to quantitative studies,and there have been significant breakthroughs in using 18F-FDG PET/CT metabolic information to predict gene expression in ICC.Radiomics and deep learning techniques have been applied to ICC for prognostic prediction and differential diagnosis.Additionally,PET/magnetic resonance imaging is increasingly demonstrating its value in this field.
文摘Soft tissue sarcomas(STS)are rare malignant tumors originating from mesoder-mal tissues with a poor prognosis,accounting for approximately 1%of all malig-nancies and comprising around 50 distinct subtypes.Conventional imaging mo-dalities,such as computed tomography(CT)and magnetic resonance imaging(MRI),primarily provide anatomical information,whereas 18F-fluorodeoxyglucose positron emission tomography/CT(18F-FDG PET/CT)integrates functional metabolic and anatomical imaging,serving as a critical complementary tool in the diagnosis and management of STS.This article reviews recent advances in the application of 18F-FDG PET/CT for STS.The advantages of 18F-FDG PET/CT in STS include:(1)Early detection of metabolic activity changes in tumors,partic-ularly when morphological alterations are insignificant;(2)Effective differen-tiation between benign and malignant soft tissue tumors,as well as aiding in distinguishing high-grade from low-grade sarcomas;(3)Identification of occult metastatic lesions,improving staging accuracy,and facilitating restaging in cases of recurrence or metastasis;(4)Utilization of parameters such as maximum stan-dardized uptake value and metabolic tumor volume to assist in tumor grading and prognostic evaluation;and(5)Monitoring treatment response to guide adjust-ments in personalized therapeutic strategies.However,18F-FDG PET/CT has limitations in diagnosis of certain STS subtypes(e.g.,myxoid liposarcoma),detection and biopsy of metastatic lymph nodes,necessitating integration with clinical evaluation and other imaging techniques.18F-FDG PET/CT is poised to play an increasingly vital role in the precision diagnosis and treatment of STS.
基金supported by the Science and Technology Innovation Team Talent Project of Hunan Province(No.2021RC4056)the clinical research foundation of the National Clinical Research Center for Geriatric Diseases(XIANGYA)(No.2020LNJJ01)+1 种基金the Natural Science Foundation of Hunan Province in China(No.2021JJ20084)the Science and Technology Innovation Program of Hunan Province(No.2021RC3020)。
文摘Polyamine metabolism dysregulation is a hallmark of many cancers,offering a promising avenue for early tumor theranostics.This study presents the development of a nuclear probe derived from spermidine(SPM)for dual-purpose tumor PET imaging and internal radiation therapy.The probe,radiolabeled with either[68Ga]Ga for diagnostic applications or[177Lu]Lu for therapeutic use,was synthesized with exceptional purity,stability,and specific activity.Extensive testing involving 12 different tumor cell lines revealed remarkable specificity towards B16 melanoma cells,showcasing outstanding tumor localization and target-to-non-target ratio.Mechanistic investigations employing polyamines,non-labeled precursor,and polyamine transport system(PTS)inhibitor,consistently affirmed the probe?s targetability through recognition of the PTS.Notably,while previous reports indicated PTS upregulation in various tumor types for targeted therapy,this study observed no positive signals,highlighting a concentration-dependent discrepancy between targeting for therapy and diagnosis.Furthermore,when labeled with[177Lu],the probe demonstrated its therapeutic potential by effectively controlling tumor growth and extending mouse survival.Investigations into biodistribution,excretion,and biosafety in healthy humans laid a robust foundation for clinical translation.This study introduces a versatile SPM-based nuclear probe with applications in precise tumor theranostics,offering promising prospects for clinical implementation.
基金This work was supported by the National Natural Science Foundation of China （No.20801024 and No.21001055）, the Natural Science Foundation of Jiangsu Province （No.BK2009077）, and the Science Foundation of Health Department of Jiangsu Province （No.H200963）.
文摘Density functional theory method has been employed to investigate the structures of the prototypical technetium-labeled diphosphonate complex 99mTc-MDP, where MDP represents methylenediphosphonic acid. A total of 14 trial structures were generated by allowing for the geometric, conformational, charge, and spin isomerism. Based on the optimized structures and calculated energies at the B3LYP/LANL2DZ level, two stable isomers were determined for the title complex. And they were further studied systematically in comparison with the experimental structure. The basis sets 6-31G＊（LANL2DZ for Tc）, 6-31G＊（cc-pVDZ-pp for Tc）, and DGDZVP have also been employed in combination with the B3LYP functional to study the basis set effect on the geometries of isomers. The optimized structures agree well with the available experimental data, and the bond lengths are more sensitive to the basis set than the bond angles. The charge distributions were studied by the Mulliken population analysis and natural bond orbital analysis. The results reflect a significant ligand-to-metal electron donation.
