Comparative Evaluation of the Biodistribution Profiles of a Series of Nonpeptidic Neurotensin Receptor-1 Antagonists Reveals a Promising Candidate for Theranostic Applications

Neurotensin receptor-1 (NTR1) is a promising target for diagnostic imaging and targeted radionuclide therapy. The aim of this study was to evaluate the biodistribution profiles of a series of newly developed diarylpyrazole-based NTR1 antagonists regarding their suitability as diagnostic and potentially radiotherapeutic agents. 3BP-227, 3BP-228, and 3BP-483 were labeled with (111)In and injected intravenously into NTR1-positive HT29 xenograft-bearing nude mice. At 3, 6, 12, and 24 h after administration, SPECT/CT images were acquired or mice were sacrificed for ex vivo determination of tissue-associated radioactivity. High-contrast tumor visualization in SPECT/CT images was achieved using the 3 compounds of this study. Ex vivo biodistribution studies confirmed a high and persistent tumor uptake, peaking at 6 h after injection for (111)In-3BP-227 (8.4 ± 3.1 percentage injected dose per gram [%ID/g]) and at 3 h after injection for (111)In-3BP-228 (10.2 ± 5.3 %ID/g) and (111)In-3BP-483 (1.9 ± 0.8 %ID/g). Tumor-to-normal-tissue ratios obtained with (111)In-3BP-227 and (111)In-3BP-228 were consistently greater than 1. On the basis of the superior biodistribution profile compared with previously reported radiolabeled NTR1 ligands, (111)In-3BP-227 is an ideal candidate for further development as a theranostic tracer.