Proof of Therapeutic Efficacy of a 177Lu-Labeled Neurotensin Receptor 1 Antagonist in a Colon Carcinoma Xenograft Model
| العنوان: | Proof of Therapeutic Efficacy of a 177Lu-Labeled Neurotensin Receptor 1 Antagonist in a Colon Carcinoma Xenograft Model |
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| المؤلفون: | Martin Rohracker, Christiane Smerling, Holger Amthauer, Aileen Höhne, Jürgen Goldschmidt, Anette Pethe, Mercedes Noriega, Ulrich Reineke, Marvin Stiebler, Jörg Schulz, Frank Osterkamp, Mathias Lukas, Franziska Stöber |
| المصدر: | Journal of Nuclear Medicine. 58:936-941 |
| بيانات النشر: | Society of Nuclear Medicine, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Oncology, medicine.medical_specialty, Biodistribution, Neurotensin receptor 1, business.industry, medicine.medical_treatment, Therapeutic effect, Urology, 030218 nuclear medicine & medical imaging, Radiation therapy, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, 030220 oncology & carcinogenesis, Internal medicine, medicine, Radioligand, Doubling time, Radiology, Nuclear Medicine and imaging, business, Ex vivo |
| الوصف: | 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 < 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. |
| تدمد: | 2159-662X 0161-5505 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::4c490a9fee3ccf56b901a6cb975baadc https://doi.org/10.2967/jnumed.116.185140 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........4c490a9fee3ccf56b901a6cb975baadc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2159662X 01615505 |
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