Novel Radiopharmaceuticals for Tumor
Synthesis and evaluation of 68Ga-labeled ODAP-PSMA targeting probe
Cao Zhen, Duan Xiaojiang, Zhang Jingming, Li Yuan, Fan Yan, Yang Xing
Published 2021-10-25
Cite as Chin J Nucl Med Mol Imaging, 2021, 41(10): 592-596. DOI: 10.3760/cma.j.cn321828-20210630-00215
Abstract
ObjectiveTo synthesize a 68Ga-labeled oxalyldiaminopropionic acid (ODAP)-urea based prostate specific membrane antigen (PSMA) targeting probe, and evaluate its properties in vitro and in vivo.
MethodsLigand P151 was synthesized by solid-phase synthesis and its Ki value was determined. The ligand P151 was added into the mixture of 68GaCl3 and NaOAc solution and was reacted at 95 ℃ for 10 min. The labeling yield and in vitro stability of 68Ga-P151 were determined by high performance liquid chromatography (HPLC). The lipid-water partition coefficient (log P) and cell binding ability were determined. The biodistribution of 68Ga-P151 in normal KM mice was determined. MicroPET imaging of 68Ga-P151 was carried out in prostate cancer 22Rv1 tumor-bearing mice and compared with 68Ga-PSMA 617. Independent sample t test was used to analyze the data.
ResultsP151 was successfully synthesized with the Ki of 0.58 nmol/L, the labeling yield more than 95% and the radiochemical purity more than 95%. After placement in saline or human serum albumin (HSA) solution at 37 ℃ for 2 h, the radiochemical purity of 68Ga-P151 was still more than 95%, indicating a good stability in vitro. The lipid-water partition coefficient (log P) of 68Ga-P151 was -2.65±0.17, indicating a good hydrophilicity. 68Ga-P151 specifically bound to PSMA in prostate cancer LNCaP cells with the uptake value of (0.83±0.04) percentage injection activity (%IA)/105 cells. Biodistribution of normal mice showed that 68Ga-P151 was mainly excreted through kidneys and other organs showed low uptake. MicroPET imaging of tumor-bearing mice showed the maximum standardized uptake value (SUVmax: 0.79±0.23 vs 0.54±0.05; t=2.12), tumor/kidney ratio (2.04±0.65 vs 1.88±0.33; t=0.44) and tumor/muscle ratio (12.83±5.18 vs 6.95±1.63; t=2.17) between 68Ga-P151 and 68Ga-PSMA 617 were not significantly different (all P>0.05).
Conclusions68Ga-P151 can be prepared simply and labeled in high yield and show improved pharmacokinetic properties in vivo. The imaging of 68Ga-P151 on PSMA positive tumor is comparable to that of 68Ga-PSMA 617, making it a potential radiopharmaceutical for the diagnosis of prostate cancer.
Key words:
Amino acids, diamino; Isotope labeling; Gallium radioisotopes; Prostate-specific membrane antigen; Positron-emission tomography; Tumor cells, cultured; Mice, nude
Contributor Information
Cao Zhen
Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China
Duan Xiaojiang
Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China
Zhang Jingming
Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China
Li Yuan
Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China
Fan Yan
Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China
Yang Xing
Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China
