Novel 18F-labeled peptides for GRP and NPY1 receptor imaging in prostate and breast cancer models by PET

Objectives Gastrin releasing peptide receptors (GRPR) and neuropeptide Y1 receptors (NPY1R) are overexpressed in a large proportion of breast and prostate cancers. The purpose of this study was to evaluate new radiofluorinated peptides that can bind with high affinity to the GRPR or NPY1R using prostate or breast tumor-bearing mice.

Methods 18F-ALK-BBN and 18F-ALK-BVD15, along with their non-radioactive standards, were prepared via click chemistry. In vitro competitive binding assays were performed on human prostate and breast cancer cell lines (PC-3 and MCF-7) to determine the inhibition constant (Ki) of 19F-ALK-BBN and 19F-ALK-BVD-15. Biodistribution studies were performed on nude mice bearing PC-3 or MCF-7 cells. Tissues of interest were collected 1 hour post-injection and counted in a gamma counter. The tissue weight and associated count per minute were used to calculate the percentage injected dose per gram of tissue (%ID/g).

Results Competitive binding assays showed a good in vitro binding with a Ki of 21 ±8 nm for 19F-ALK-BBN and 31 ±18 nm nM for 19F-ALK-BVD15. Biodistribution studies showed a rapid clearance of 18F-ALK-BBN through the hepatobiliary tract and low pancreas and tumor uptake in PC-3 tumor-bearing mice. %ID/g of 18F-ALK-BBN in liver, pancreas and tumor was 0.8 ±0.3, 1.22 ±0.4 and 0.14 ±0.04 respectively. 18F-ALK-BVD15 showed improved tracer bioavailability, but no significant uptake of tumor was observed in MCF-7 tumor-bearing mice.

Conclusions 18F-ALK-BBN, despite good in vitro binding, has an extremely rapid clearance in vivo through the hepatobiliary tract and no GRP receptor-mediated binding was observed. 18F-ALK-BVD15 has a suitable biodistribution but no significant receptor-mediated tumor uptake was seen in NPY1R positive MCF-7 cells. Thus, more hydrosoluble peptide and prosthetic group variants have been synthesized and are being tested to improve tumor binding