Prostate cancer imaging of FSHR antagonist modified with a hydrophilic linker

Abstract

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.

In vivo targeting of metastatic breast cancer via tumor vasculature-specific nano-graphene oxide

“…Although decent tumor uptake was shown, fast washout of the tracer from the tumors and a short half-life of 18 F (118 min) limited its application in the longitudinal tumor detection. Same research group made an extra effort in a follow-up study to optimize its in vivo kinetics by incorporation of a hydrophilic linker [23], however the overall tumor imaging capacity did not get improved. Compared with other ligands, antibodies usually possess stronger and more selective target recognition and thus we chose to use 64 Cu-labeled monoclonal antibody (mAb) for PET imaging of FSHR in different cancer types [24].…”

Live imaging of follicle stimulating hormone receptors in gonads and bones using near infrared II fluorophore

“…30,31 The present approach could provide new tools for monitoring tumor progression in vivo . 32 There are only a few studies dealing with molecular imaging reagents with sensitivity to the FSH receptor, 33 the others focus on FSH receptor expressing cancer cells/tumors and vasculature associated with tumor development and progression.…”

Targeting HER2-positive gastric cancer with a novel 18F-labeled ZHER2:342 probe

“…Our teams have successfully accomplished 18 F radiolabeling of several vectors using this process. [30][31][32] Hence, we also chose this method to realize site-specic labelling by introducing a unique cysteine to the N-terminal of Z HER2:342 . Gly-Gly-Gly-Arg-Asp-Asn (GGGRDN) is a new kind of hydrophilic linker with favorable properties.…”