Abstract
PET radioligands with low molar activity (MA) may underestimate the quantity of the target of interest because of competitive binding of the target with unlabeled ligand. The aim of this study was to evaluate the change in the whole-body distribution of 18F-PSMA-1007 targeting prostate-specific membrane antigen (PSMA) when solutions with different peptide concentrations are used. Methods: Mouse xenograft models of LNCaP (PSMA-positive prostate cancer) (n = 18) were prepared and divided into 3 groups according to the peptide concentration injected: a high-MA group (1,013 ± 146 GBq/μmol; n = 6), a medium-MA group (100.7 ± 23.1 GBq/μmol; n = 6), and a low-MA group (10.80 ± 2.84 GBq/μmol; n = 6). Static PET scans were performed 1 h after injection (scan duration, 10 min). SUVmean in tumor and normal organs was compared by the multiple-comparison test. Immunohistochemical staining and Western blot analysis were performed to confirm expression of PSMA in tumor, salivary gland, and kidney. Results: The low-MA group (SUVmean, 1.12 ± 0.30) showed significantly lower uptake of 18F-PSMA-1007 in tumor than did the high-MA group (1.97 ± 0.77) and the medium-MA group (1.81 ± 0.57). On the other hand, in salivary gland, both the low-MA group (SUVmean, 0.24 ± 0.04) and the medium-MA group (0.57 ± 0.08) showed significantly lower uptake than the high MA group (1.27 ± 0.28). The tumor-to-salivary gland SUVmean ratio was 1.73 ± 0.55 in the high-MA group, 3.16 ± 0.86 in the medium-MA group, and 4.78 ± 1.29 in the low-MA group. The immunohistochemical staining and Western blot analysis revealed significant overexpression of PSMA in tumor and low expression in salivary gland and kidney. Conclusion: A decrease in the MA level of the injected 18F-PSMA-1007 solution resulted in decreased uptake in tumor and, to a greater degree, in normal salivary gland. Thus, there is a possibility of minimizing the adverse effects in salivary gland by setting an appropriate MA level in PSMA-targeting therapy.
Highlights
Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer cells and is considered a novel target of theranostics in prostate cancer [1,2]
There were no significant differences in tumor size among the 3 groups, the larger trend was observed in the high-molar activity (MA) group because of the variability in size
PSMA overexpression in the plasma membrane of the tumor cells was confirmed in tumor for all 3 groups
Summary
Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer cells and is considered a novel target of theranostics in prostate cancer [1,2]. Giesel et al reported the superiority of 18F-PSMA-1007 for the diagnosis of pelvic metastases, focusing on its minimal uptake in the urinary tract [4] They showed a good correlation between the results of pretreatment PET evaluation and distribution of the therapeutic agent 177Lu-PSMA-617 [5]. Chatalic into a reaction vessel with 0.075 M tetrabutylammonium HCO3 soluet al., in a preclinical model using SPECT, showed that coinjection tion (600 mL) This solution was azeotropically dried with acetonitrile of a PSMA inhibitor decreased the absorbed dose to the kidney (1 mL). Different peptide concentrations of nonradiolabeled PSMA between diagnostic PET and radionuclide therapy might result in different degrees of radioligand accumulation in the target tissues and normal organs. In this study on mouse xenograft models, we evaluated changes in whole-body distribution using 18F-PSMA-1007 solutions with different peptide concentrations to optimize the MA level for subsequent targeted radionuclide therapy. These cartridges were washed with 5% ethanol solution (23 mL) and 30% ethanol solution (3 mL) for removal of any chemical or radiochemical impurities. 18F-PSMA-1007 trapped on the cartridge was eluted with 30% ethanol solution (4 mL) into the product vial containing 0.9% NaCl solution (11 mL) plus 100 mg of sodium ascorbate
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