PT  - JOURNAL ARTICLE
AU  - Jörg Schulz
AU  - Martin Rohracker
AU  - Marvin Stiebler
AU  - Jürgen Goldschmidt
AU  - Oliver S. Grosser
AU  - Frank Osterkamp
AU  - Annette Pethe
AU  - Ulrich Reineke
AU  - Christiane Smerling
AU  - Holger Amthauer
TI  - Comparative Evaluation of the Biodistribution Profiles of a Series of Nonpeptidic Neurotensin Receptor-1 Antagonists Reveals a Promising Candidate for Theranostic Applications
AID  - 10.2967/jnumed.115.170530
DP  - 2016 Jul 01
TA  - Journal of Nuclear Medicine
PG  - 1120--1123
VI  - 57
IP  - 7
4099  - http://jnm.snmjournals.org/content/57/7/1120.short
4100  - http://jnm.snmjournals.org/content/57/7/1120.full
SO  - J Nucl Med2016 Jul 01; 57
AB  - 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. Methods: 3BP-227, 3BP-228, and 3BP-483 were labeled with 111In 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. Results: 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 111In-3BP-227 (8.4 ± 3.1 percentage injected dose per gram [%ID/g]) and at 3 h after injection for 111In-3BP-228 (10.2 ± 5.3 %ID/g) and 111In-3BP-483 (1.9 ± 0.8 %ID/g). Tumor–to–normal-tissue ratios obtained with 111In-3BP-227 and 111In-3BP-228 were consistently greater than 1. Conclusion: On the basis of the superior biodistribution profile compared with previously reported radiolabeled NTR1 ligands, 111In-3BP-227 is an ideal candidate for further development as a theranostic tracer.