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
Areas of uptake on positron emission tomography with 1-(2-[18F]fluoro-1-[hydroxymethyl]ethoxy)methyl-2-nitroimidazole (FRP170 PET), a hypoxic cell radiotracer, can include regions retaining highly proliferative activi...Areas of uptake on positron emission tomography with 1-(2-[18F]fluoro-1-[hydroxymethyl]ethoxy)methyl-2-nitroimidazole (FRP170 PET), a hypoxic cell radiotracer, can include regions retaining highly proliferative activity despite tissue hypoxia. The aim of this study was to clarify whether FRP170 image can detect densely populated hypoxic areas without proliferating potential in glioblastoma. We performed FRP170 PET scan and L-methyl-11C-methionine (MET) PET scan in eight patients with non-treated glioblastoma. Standardized uptake values (SUVs) within tumor and apparent normal brain were measured on each FRP170 and MET image for all patients. To visualize actively proliferative areas on MET image we initially extracted pixels showing a ratio of SUV in tumor to SUV in normal brain (T/N) > 1.6. For FRP170 image, we changed the thresholds between minimum SUV and maximum SUV in tumor. Pixels showing SUV above each threshold were extracted and superimposed on previously extracted pixels from MET image. We estimated whether pixels extracted with MET and FRP170 were visually separated on superimposed image for each pa-tient. When no threshold was established, uptake areas on MET image and FRP170 image overlapped widely on superimposed image in all patients. The higher threshold for FRP170 image diminished FRP170-extracted pixels, and shrunk overlapped areas on superimposed image. However, pixels extracted from FRP170 images could not be completely separated from pixels extracted from MET images in all patients, even with threshold raised to almost maximum SUV. The current findings suggest that uptake areas on FRP170 PET scan necessarily include proliferating areas in glioblastoma.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Areas of uptake on positron emission tomography with 1-(2-[18F]fluoro-1-[hydroxymethyl]ethoxy)methyl-2-nitroimidazole (FRP170 PET), a hypoxic cell radiotracer, can include regions retaining highly proliferative activity despite tissue hypoxia. The aim of this study was to clarify whether FRP170 image can detect densely populated hypoxic areas without proliferating potential in glioblastoma. We performed FRP170 PET scan and L-methyl-11C-methionine (MET) PET scan in eight patients with non-treated glioblastoma. Standardized uptake values (SUVs) within tumor and apparent normal brain were measured on each FRP170 and MET image for all patients. To visualize actively proliferative areas on MET image we initially extracted pixels showing a ratio of SUV in tumor to SUV in normal brain (T/N) > 1.6. For FRP170 image, we changed the thresholds between minimum SUV and maximum SUV in tumor. Pixels showing SUV above each threshold were extracted and superimposed on previously extracted pixels from MET image. We estimated whether pixels extracted with MET and FRP170 were visually separated on superimposed image for each pa-tient. When no threshold was established, uptake areas on MET image and FRP170 image overlapped widely on superimposed image in all patients. The higher threshold for FRP170 image diminished FRP170-extracted pixels, and shrunk overlapped areas on superimposed image. However, pixels extracted from FRP170 images could not be completely separated from pixels extracted from MET images in all patients, even with threshold raised to almost maximum SUV. The current findings suggest that uptake areas on FRP170 PET scan necessarily include proliferating areas in glioblastoma.
