Prostate cancer imaging of FSHR antagonist modified with a hydrophilic linker.
Follicle-stimulating hormone receptor (FSHR) is selectively expressed in endothelial cells of prostate cancer (PCa) and becomes a potential target for tumor diagnosis and therapy. (18)F-Al-NOTA-MAL-FSH1 is a promising PET imaging probe for targeting FSHR; however, the unfavorable abdominal backgrounds may hamper clinical translation. GGGRDN is a new hydrophilic linker, which can improve the imaging quality of radiolabeled peptides. In this study, GGGRDN-FSH1 (denoted as FSH2) was designed and conjugated with NOTA-MAL for (18)F-Al radiolabeling. NOTA-MAL-FSH2 was obtained with about 50% yield and labeled using (18)F-Al in a one-step method within 20 min with a yield of 41.46 ± 10.36% (non-decay-corrected). The radiochemical purity was more than 95% and the specific activity was more than 50 GBq/µmol. The in vitro stability studies were determined in PBS and human serum. (18)F-Al-NOTA-MAL-FSH2 remained stable in PBS and human serum. Balb/c nude mice bearing PC-3 human PCa were used for in vivo study. PC-3 tumors were clearly visualized with good contrast to background through microPET. ROI analysis showed the tumor uptake values were 2.68 ± 0.52 and 1.97 ± 0.61%ID/g at 30 and 60 min post injection (p.i.), respectively. Biodistribution studies showed that the accumulations of (18)F-Al-NOTA-MAL-FSH2 in liver and intestine were 0.47 ± 0.11 and 0.12 ± 0.03%ID/g respectively at 60 min p.i. FSHR-binding specificity was also demonstrated by reduced tumor uptake after coinjection of excessive unlabeled FSH2. In conclusion, (18)F-Al-NOTA-MAL-FSH2 was successfully prepared in a one-step method and showed better pharmacokinetics than (18) F-Al-NOTA-MAL-FSH1. Favorable preclinical study revealed that (18)F-Al-NOTA-MAL-FSH2 appears to be a promising candidate for FSHR-positive tumor imaging.
Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
Chen
C
Zhu
Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
Qing
Q
Xu
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, 20 Qianrong Road, Wuxi, 214063, China.
Donghui
D
Pan
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, 20 Qianrong Road, Wuxi, 214063, China.
Yuping
Y
Xu
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, 20 Qianrong Road, Wuxi, 214063, China.
Ping
P
Liu
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, 20 Qianrong Road, Wuxi, 214063, China.
Runlin
R
Yang
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, 20 Qianrong Road, Wuxi, 214063, China.
Lizhen
L
Wang
Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
Xinchen
X
Sun
Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.|Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, 20 Qianrong Road, Wuxi, 214063, China.
Shineng
S
Luo
Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.|Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, 20 Qianrong Road, Wuxi, 214063, China.
Min
M
Yang
D000818:Animals; D045744:Cell Line, Tumor; D005462:Fluorine Radioisotopes / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D008297:Male; D051379:Mice; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry; D049268:Positron-Emission Tomography / Q000379:methods*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D011962:Receptors, FSH / Q000008:administration & dosage* / Q000737:chemistry; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
D005462:Fluorine Radioisotopes; D010455:Peptides; D011962:Receptors, FSH
18F; FSHR; microPET; prostate cancer