PET Imaging of FSHR Expression in Tumors with 68Ga-Labeled FSH1 Peptide

FSHR is an appealing target for cancer theranostics. Radiolabeled FSH1 and its derivatives have shown potential to in vivo detect FSHR expression. However, moderate labeling yields (similar to 50% nondecay-corrected) may partially limit their wide use. Ga-68 is an excellent PET nuclide due to availability, nearly quantitative reaction, and short physical half-life. In this study, Ga-68 labeled FSH1 peptide was developed for imaging of FSHR in cancers. In vitro studies and MicroPET imaging were performed in PC-3 prostate tumor model. [Ga-68] Ga-NOTA-MAL-FSH1 can be produced within 20 min with 93.2 +/- 2.1% yield and the radiochemical purity was greater than 95%. It showed that [Ga-68] Ga-NOTA-MAL-FSH1 possessed FSHR binding affinities. The tracer was stable in PBS and human serum for at least 2 hours. MicroPET imaging revealed that the PC-3 xenografts were clearly visualized and the tumor uptakes were 1.87 +/- 0.10, 1.26 +/- 0.06, and 0.71 +/- 0.10% ID/g at 0.5, 1 h, and 2 h postinjection. The corresponding tumor to blood and tumor to muscle ratios were 1.77 +/- 0.70, 7.94 +/- 1.35, and 10.37 +/- 1.16 and 7.42 +/- 0.46, 26.13 +/- 2.99, and 36.40 +/- 2.54, respectively. FSHR binding specificity was also demonstrated by reduced tumor uptake of [Ga-68] Ga-NOTA-MAL-FSH1 after coinjecting excess unlabeled FSH1 peptide. The favorable characters of [Ga-68] Ga-NOTA-MAL-FSH1 such as convenient synthesis and specific tumor uptake warrant its further investigation for FSHR expression imaging.