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
Two novel triflate precursors for radiolabelling of L-tyrosine in positron emission tomography (PET) for tumor imaging,O-(2-trifluoromethanesulfonyloxyethyl)-N-(tert-butoxycarbonyl)-L-tyrosine methyl ester 9a and O-(2...Two novel triflate precursors for radiolabelling of L-tyrosine in positron emission tomography (PET) for tumor imaging,O-(2-trifluoromethanesulfonyloxyethyl)-N-(tert-butoxycarbonyl)-L-tyrosine methyl ester 9a and O-(2-trifluoromethanesulfonyloxyethyl)-N-(tert-butoxycarbonyl)-L-tyrosine tert-butyl ester 9b,are synthesized. The triflate agent,9a or 9b,is prepared by esterification of methanol or transesterification of tert-butyl acetate with L-tyrosine,protection of the amine group with di-tert-butyl dicarbonate,alkylation with chlorohydrin,and triflation with trifluoromethanesulfonic anhydride in four steps with overall yields of 30% and 15%,respectively.展开更多
O-(2-[18F]fluoroethyl) -L-tyrosine([18F]FET) ,a fluorine-18 labeled analogue of tyrosine,has been syn-thesized and biologically evaluated in tumor-bearing mice. The whole synthesis procedure is com-pleted within 50 mi...O-(2-[18F]fluoroethyl) -L-tyrosine([18F]FET) ,a fluorine-18 labeled analogue of tyrosine,has been syn-thesized and biologically evaluated in tumor-bearing mice. The whole synthesis procedure is com-pleted within 50 min. The radiochemical yield is about 40%(no decay corrected) and radiochemical purity more than 97% after simplified solid phase extraction. [18F]FET shows rapid,high uptake and long retention in the tumor as well as low uptake in the brain. The ratios of tumor-to-muscle(T/M) and tumor-to-blood(T/B) of [18F]FET are similar to those of [18F]FDG,but the ratios of tumor-to-brain(T/Br) are 2-3 times higher than that of [18F]FDG. Autoradiography of [18F]FET demonstrates a remarkable accumulation in melanoma with high contrast. It appears to be a probable competitive candidate for melanoma imaging with PET.展开更多
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Two novel triflate precursors for radiolabelling of L-tyrosine in positron emission tomography (PET) for tumor imaging,O-(2-trifluoromethanesulfonyloxyethyl)-N-(tert-butoxycarbonyl)-L-tyrosine methyl ester 9a and O-(2-trifluoromethanesulfonyloxyethyl)-N-(tert-butoxycarbonyl)-L-tyrosine tert-butyl ester 9b,are synthesized. The triflate agent,9a or 9b,is prepared by esterification of methanol or transesterification of tert-butyl acetate with L-tyrosine,protection of the amine group with di-tert-butyl dicarbonate,alkylation with chlorohydrin,and triflation with trifluoromethanesulfonic anhydride in four steps with overall yields of 30% and 15%,respectively.
基金Supported by the Knowledge Innovation Project of Chinese Academy of Sciences (No. KJCX1-SW-08) the National Natural Science Foundation of China (Grant No. 30371634)
文摘O-(2-[18F]fluoroethyl) -L-tyrosine([18F]FET) ,a fluorine-18 labeled analogue of tyrosine,has been syn-thesized and biologically evaluated in tumor-bearing mice. The whole synthesis procedure is com-pleted within 50 min. The radiochemical yield is about 40%(no decay corrected) and radiochemical purity more than 97% after simplified solid phase extraction. [18F]FET shows rapid,high uptake and long retention in the tumor as well as low uptake in the brain. The ratios of tumor-to-muscle(T/M) and tumor-to-blood(T/B) of [18F]FET are similar to those of [18F]FDG,but the ratios of tumor-to-brain(T/Br) are 2-3 times higher than that of [18F]FDG. Autoradiography of [18F]FET demonstrates a remarkable accumulation in melanoma with high contrast. It appears to be a probable competitive candidate for melanoma imaging with PET.
