Gallium-68-Labeled KISS1-54 Peptide for Mapping KISS1 Receptor via PET: Initial Evaluation in Human Tumor Cell Lines and in Tumor-Bearing Mice

Kisspeptins (KPs, KISS1) and their receptor (KISS1R) play a pivotal role as metastasis suppressor for many cancers. Low or lost KP expression is associated with higher tumor grade, increased metastatic potential, and poor prognosis. Therefore, KP expression has prognostic relevance and correlates with invasiveness in cancers. Furthermore, KISS1R represents a very promising target for molecular imaging and therapy for KISS1R-expressing tumors. The goal of this study was to evaluate the developed KISS1-54 derivative, [ 68 Ga]KISS1-54, as a PET-imaging probe for KISS1R-expressing tumors. The NODAGA-KISS1-54 peptide was labeled by Gallium-68, and the stability of the resulting [ 68 Ga]KISS1-54 evaluated in injection solution and human serum, followed by an examination in different KISS1R-expressing tumor cell lines, including HepG2, HeLa, MDA-MB-231, MCF7, LNCap, SK-BR-3, and HCT116. Finally, [ 68 Ga]KISS1-54 was tested in LNCap- and MDA-MB-231-bearing mice, using µ-PET, assessing its potential as an imaging probe for PET. [ 68 Ga]KISS1-54 was obtained in a 77 ± 7% radiochemical yield and at a >99% purity. The [ 68 Ga]KISS1-54 cell uptake amounted to 0.6–4.4% per 100,000 cells. Moreover, the accumulation of [ 68 Ga]KISS1-54 was effectively inhibited by nonradioactive KISS1-54. In [ 68 Ga]KISS1-54-PET, KISS1R-positive LNCap-tumors were clearly visualized as compared to MDA-MB-231-tumor implant with predominantly intracellular KISS1R expression. Our first results suggest that [ 68 Ga]KISS1-54 is a promising candidate for a radiotracer for targeting KISS1R-expressing tumors via PET.