Preliminary Study of a Novel 68Ga-Labeled Probe Targeting Neuropilin-1 for Tumor Diagnosis

Abstract

Neuropilin-1 (NRP-1), a transmembrane protein related to tumor progression and invasion, presents potential as a prospective biomarker for tumor diagnosis and therapy. Positron emission tomography (PET) is acknowledged as an ideal modality for accurately monitoring NRP-1 expression in vivo due to its superior sensitivity and resolution. In this study, a novel peptide-based PET imaging probe, [⁶⁸Ga]Ga-DOTA-NEP, was successfully developed for specifically visualizing NRP-1 expression in tumors. The probe was prepared with a radiochemical yield (RCY) and radiochemical purity (RCP) greater than 95%, a molar activity of 13.28 ± 0.97 GBq/μmol, and a lipid–water partition coefficient (log P) of −2.20 ± 0.13. In vitro stability assay showed that the probe possessed sufficient stability for biological evaluation. The cellular uptake of the probe in U87 and A549 cells (4.91 ± 0.14 and 4.58 ± 0.40%AD) with high expression of NRP-1 was higher than that observed in NRP-1 negative cells HCT116 and NCI-H1299 (2.84 ± 0.23 and 1.76 ± 0.25%AD) at 1 h. In vivo PET imaging revealed that the maximum tumor uptake of the probe in U87 (7.20 ± 1.03%ID/mL) and A549 (5.90 ± 0.57%ID/mL) tumor-bearing mice was also markedly higher compared to that in HCT116 (3.09 ± 0.43%ID/mL) and NCI-H1299 (2.90 ± 0.70%ID/mL) tumor-bearing mice. Ex vivo analysis further confirmed the targeting specificity of the probe [⁶⁸Ga]Ga-DOTA-NEP for NRP-1. These results suggest that [⁶⁸Ga]Ga-DOTA-NEP could serve as a promising PET imaging probe for the diagnosis of NRP-1 positive tumors.