PT - JOURNAL ARTICLE AU - Schulz, Jörg AU - Rohracker, Martin AU - Stiebler, Marvin AU - Goldschmidt, Jürgen AU - Stöber, Franziska AU - Noriega, Mercedes AU - Pethe, Anette AU - Lukas, Mathias AU - Osterkamp, Frank AU - Reineke, Ulrich AU - Höhne, Aileen AU - Smerling, Christiane AU - Amthauer, Holger TI - Proof of Therapeutic Efficacy of a <sup>177</sup>Lu-Labeled Neurotensin Receptor 1 Antagonist in a Colon Carcinoma Xenograft Model AID - 10.2967/jnumed.116.185140 DP - 2017 Jun 01 TA - Journal of Nuclear Medicine PG - 936--941 VI - 58 IP - 6 4099 - http://jnm.snmjournals.org/content/58/6/936.short 4100 - http://jnm.snmjournals.org/content/58/6/936.full SO - J Nucl Med2017 Jun 01; 58 AB - Increased expression of neurotensin receptor 1 (NTR1) has been shown in a large number of tumor entities such as pancreatic or colon carcinoma. Hence, this receptor is a promising target for diagnostic imaging and radioligand therapy. Using the favorable biodistribution data of the NTR1-targeting agent 111In-3BP-227, we investigated the therapeutic effect of its 177Lu-labeled analog on the tumor growth of NTR1-positive HT29 colon carcinoma xenografts. Methods: 3BP-227 was labeled with 177Lu. To assess its biodistribution properties, SPECT and CT scans of HT29-xenografted nude mice injected with 177Lu-3BP-227 were acquired, and ex vivo tissue activity was determined. To evaluate therapeutic efficacy, 2 groups of mice received the radiopharmaceutical in a median dose of either 165 MBq (129–232 MBq, n = 10) or 110 MBq (82–116 MBq, n = 10), whereas control mice were injected with vehicle (n = 10). Tumor sizes and body weights were monitored for up to 49 d. Renal function and histologic morphology were evaluated. Results: Whole-body SPECT/CT images allowed clear tumor visualization with low background activity and high tumor-to-kidney and -liver ratios. Ex vivo biodistribution data confirmed high and persistent uptake of 177Lu-3BP-227 in HT29 tumors (19.0 ± 3.6 vs. 2.7 ± 1.6 percentage injected dose per gram at 3 and 69 h after injection, respectively). The application of 177Lu-3BP-227 resulted in a distinct delay of tumor growth. Median tumor doubling time for controls was 5.5 d (interquartile range [IQR], 2.8–7.0), compared with 17.5 d (IQR, 5.5–22.5 d) for the 110-MBq and 41.0 d (IQR, 27.5–55.0) for the 165-MBg group. Compared with controls, median relative tumor volume at day 23 after injection was reduced by 55% (P = 0.034) in the 110-MBq and by 88% (P &lt; 0.01) in the 165-MBq group. Renal histology and clinical chemistry results did not differ between radiotherapy groups and controls, suggesting absence of therapy-induced acute renal damage. Conclusion: These data demonstrate that the novel NTR1-targeting theranostic agent 3BP-227 is an effective and promising candidate for radioligand therapy, with a favorable preliminary safety profile and high potential for clinical translation.