Prostate cancer (PCa) is the second most common type of cancer among men worldwide and one of the leading causes of cancer-related deaths. According to data from the World Health Organization (WHO), this cancer causes...Prostate cancer (PCa) is the second most common type of cancer among men worldwide and one of the leading causes of cancer-related deaths. According to data from the World Health Organization (WHO), this cancer causes hundreds of thousands of new cases and tens of thousands of male deaths globally each year. The incidence of PCa varies across different regions and populations, generally being higher in developed countries. This disparity may be attributed to lifestyle factors and the widespread availability of screening and diagnostic technologies. Prostate-specific membrane antigen (PSMA) is a membrane-bound enzyme predominantly expressed in prostate tissue and PCa cells, with lower expression in normal tissues. This high expression makes PSMA a critical target for the diagnosis and treatment of PCa, particularly in the field of molecular imaging and radiopharmaceutical therapy. Recently, various studies have emerged on radiopharmaceuticals developed based on PSMA ligands, which can be used to specifically identify and locate PCa cells. Research on the radiomics of these novel drugs has also been updated. This article will discuss the role and limitations of PSMA PET in the diagnosis and management of PCa treatment.展开更多
Introduction: 68Ga-PSMA-11 is considered the gold standard in detection of micro and oligometastases in advanced prostate cancer, being used for therapeutic planning, as well as, potentially, for evaluating response t...Introduction: 68Ga-PSMA-11 is considered the gold standard in detection of micro and oligometastases in advanced prostate cancer, being used for therapeutic planning, as well as, potentially, for evaluating response to treatment. The development of ready-to-use lyophilized kit of PSMA-11 adds quality and safety to the routine use of this radiopharmaceutical and represents a pharmacotechnical challenge as it must preserve the integrity and specificity of the ligand. Methods: PSMA-11 kit formulation was proposed, considering radiolabeling parameters and the preservation of the peptide during the lyophilization process, using mannitol as an excipient. Critical temperature characterization studies were carried out using DSC equipment and the freeze-drying process was developed. The direct radiolabeling conditions were evaluated and standardized using 68Ge/68Ga generator eluate from two different manufacturers (ITG and Eckert & Ziegler). The radiochemical purity was evaluated by TLC and HPLC. Biological evaluation was carried out with lyophilized PSMA-11 to demonstrate the integrity of the peptide and preservation of biological activity after the lyophilization process. Results: Based on critical temperature characterization studies, the freeze-drying cycle was designed to reach a freezing temperature of around −40˚C and primary drying at 2˚C. Using 20 mg of mannitol, an intact and elegant lyophilized cake was obtained. PSMA-11 lyophilized kit was directly labeled with 68Ga eluate from 68Ge/68Ga GMP generators (ITG and Eckert & Ziegler) resulting in % RP > 95% at pH 4.0 to 4.5. The results obtained from in vitro and in vivo biological competition studies confirmed the preservation of PSMA-11 affinity for the receptor after lyophilization. Conclusion: A lyophilized formulation (Kit) of PSMA-11 was successfully obtained, which preserved the integrity and biological activity of the peptide and guaranteed radiolabeling efficiency.展开更多
Objectives:Due to systematic side effects,there is a growing interest in nanoparticle formulation of anticancer drugs.Here,we aimed to synthesize poly(styrene-alt-maleic anhydride)cross-linked by melamine(PSMA/Me)and ...Objectives:Due to systematic side effects,there is a growing interest in nanoparticle formulation of anticancer drugs.Here,we aimed to synthesize poly(styrene-alt-maleic anhydride)cross-linked by melamine(PSMA/Me)and coated with magnetite nanoparticles(MNPs)PSMA/Me/Fe_(3)O_(4).In addition,we aimed to load paclitaxel(PTX)into PSMA/Me/Fe_(3)O_(4)for drug delivery and anticancer investigations.Methods:Novel PSMA/Me was synthesized via free radical copolymerization,coated with Fe_(3)O_(4),and then used as a transporter for PTX delivery.Fabricated copolymer was characterized using SEM,TGA,and XRD techniques.Drug release rate and loading efficiency were investigated.Human ovarian cancer cells(Skov-3)and breast cancer cells(MCF-7 cells)were incubated with the serial concentration of either free PTX or PSMA/Me/Fe_(3)O_(4)/PTX for cell viability and IC_(50)analysis for 24 and 48 h.Results:Characterization methods confirmed PSMA/Me copolymer formation.The results showed a significant encapsulation efficiency of 83%.The drug release analysis exhibited that PSMA/Me/Fe_(3)O_(4)/PTX may be considered pH-sensitive nanocarriers.PSMA/Me/Fe_(3)O_(4)/PTX reduced cell viability both dose and time-dependently(p<0.05).IC50 values of PSMA/Me/Fe_(3)O_(4)/PTX were low when compared to free PTX either 24 or 48 h post-treatment.Conclusions:Our results indicated that PSMA/Me/Fe_(3)O_(4)/PTX was more cytotoxic than PTX in both cancer cells.Findings indicated the potential of PSMA/Me/Fe_(3)O_(4)/PTX as an anticancer nanocarrier system.展开更多
文摘Prostate cancer (PCa) is the second most common type of cancer among men worldwide and one of the leading causes of cancer-related deaths. According to data from the World Health Organization (WHO), this cancer causes hundreds of thousands of new cases and tens of thousands of male deaths globally each year. The incidence of PCa varies across different regions and populations, generally being higher in developed countries. This disparity may be attributed to lifestyle factors and the widespread availability of screening and diagnostic technologies. Prostate-specific membrane antigen (PSMA) is a membrane-bound enzyme predominantly expressed in prostate tissue and PCa cells, with lower expression in normal tissues. This high expression makes PSMA a critical target for the diagnosis and treatment of PCa, particularly in the field of molecular imaging and radiopharmaceutical therapy. Recently, various studies have emerged on radiopharmaceuticals developed based on PSMA ligands, which can be used to specifically identify and locate PCa cells. Research on the radiomics of these novel drugs has also been updated. This article will discuss the role and limitations of PSMA PET in the diagnosis and management of PCa treatment.
文摘Introduction: 68Ga-PSMA-11 is considered the gold standard in detection of micro and oligometastases in advanced prostate cancer, being used for therapeutic planning, as well as, potentially, for evaluating response to treatment. The development of ready-to-use lyophilized kit of PSMA-11 adds quality and safety to the routine use of this radiopharmaceutical and represents a pharmacotechnical challenge as it must preserve the integrity and specificity of the ligand. Methods: PSMA-11 kit formulation was proposed, considering radiolabeling parameters and the preservation of the peptide during the lyophilization process, using mannitol as an excipient. Critical temperature characterization studies were carried out using DSC equipment and the freeze-drying process was developed. The direct radiolabeling conditions were evaluated and standardized using 68Ge/68Ga generator eluate from two different manufacturers (ITG and Eckert & Ziegler). The radiochemical purity was evaluated by TLC and HPLC. Biological evaluation was carried out with lyophilized PSMA-11 to demonstrate the integrity of the peptide and preservation of biological activity after the lyophilization process. Results: Based on critical temperature characterization studies, the freeze-drying cycle was designed to reach a freezing temperature of around −40˚C and primary drying at 2˚C. Using 20 mg of mannitol, an intact and elegant lyophilized cake was obtained. PSMA-11 lyophilized kit was directly labeled with 68Ga eluate from 68Ge/68Ga GMP generators (ITG and Eckert & Ziegler) resulting in % RP > 95% at pH 4.0 to 4.5. The results obtained from in vitro and in vivo biological competition studies confirmed the preservation of PSMA-11 affinity for the receptor after lyophilization. Conclusion: A lyophilized formulation (Kit) of PSMA-11 was successfully obtained, which preserved the integrity and biological activity of the peptide and guaranteed radiolabeling efficiency.
文摘Objectives:Due to systematic side effects,there is a growing interest in nanoparticle formulation of anticancer drugs.Here,we aimed to synthesize poly(styrene-alt-maleic anhydride)cross-linked by melamine(PSMA/Me)and coated with magnetite nanoparticles(MNPs)PSMA/Me/Fe_(3)O_(4).In addition,we aimed to load paclitaxel(PTX)into PSMA/Me/Fe_(3)O_(4)for drug delivery and anticancer investigations.Methods:Novel PSMA/Me was synthesized via free radical copolymerization,coated with Fe_(3)O_(4),and then used as a transporter for PTX delivery.Fabricated copolymer was characterized using SEM,TGA,and XRD techniques.Drug release rate and loading efficiency were investigated.Human ovarian cancer cells(Skov-3)and breast cancer cells(MCF-7 cells)were incubated with the serial concentration of either free PTX or PSMA/Me/Fe_(3)O_(4)/PTX for cell viability and IC_(50)analysis for 24 and 48 h.Results:Characterization methods confirmed PSMA/Me copolymer formation.The results showed a significant encapsulation efficiency of 83%.The drug release analysis exhibited that PSMA/Me/Fe_(3)O_(4)/PTX may be considered pH-sensitive nanocarriers.PSMA/Me/Fe_(3)O_(4)/PTX reduced cell viability both dose and time-dependently(p<0.05).IC50 values of PSMA/Me/Fe_(3)O_(4)/PTX were low when compared to free PTX either 24 or 48 h post-treatment.Conclusions:Our results indicated that PSMA/Me/Fe_(3)O_(4)/PTX was more cytotoxic than PTX in both cancer cells.Findings indicated the potential of PSMA/Me/Fe_(3)O_(4)/PTX as an anticancer nanocarrier system.
