Five Stabilized 111In-labeled neurotensin analogs in nude mice bearing HT29 tumors
| Autor: | Jack L. Erion, Moniaue de Visser, Arnold G. Vulto, Bert F. Bernard, Eric P. Krenning, Marion de Jong, Suzanne M. Verwijnen, Paul J. J. M. Janssen, Wouter A.P. Breeman, Ananth Srinivasan |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty Biodistribution Arginine Lysine Transplantation Heterologous Mice Nude Kidney chemistry.chemical_compound Mice In vivo Internal medicine medicine Animals Humans Radiology Nuclear Medicine and imaging Tissue Distribution Receptor Neurotensin Pharmacology Analysis of Variance Chemistry Indium Radioisotopes General Medicine Pentetic Acid medicine.disease Molecular biology Radiography Endocrinology Oncology Colonic Neoplasms Adenocarcinoma Exocrine pancreatic cancer Oligopeptides |
| Zdroj: | Cancer biotherapyradiopharmaceuticals. 22(3) |
| ISSN: | 1084-9785 |
| Popis: | Neurotensin (NT) receptors are overexpressed in different human tumors, such as human ductal pancreatic adenocarcinoma. New stable neurotensin analogs with high receptor affinity have been synthesized by replacing arginine residues with lysine and arginine derivatives. The aim of this study was to explore the biodistribution, tumor uptake, kidney localization, and stability characteristics of these new analogs in order to develop new diagnostic tools for exocrine pancreatic cancer. Four (111)In-labeled DTPA-chelated NT analogs and one (111)In-labeled DOTA-chelated NT analog were evaluated in NMRI nude mice bearing NT receptor-positive HT29 tumors. Experiments with a coinjection of unlabeled NT or lysine were performed to investigate receptor-mediated uptake and kidney protection, respectively. In addition, the in vivo serum stability of the most promising analog was analyzed. In the biodistribution study in mice, at 4 hours postinjection, a low percentage of the injected dose per gram (%ID/g) of tissue for all compounds was found in NT receptor-negative organs, such as the blood, spleen, pancreas, liver, muscle, and femur. A high uptake was found in the colon, intestine, kidneys, and in implanted HT29 tumors. The coinjection of excess unlabeled neurotensin significantly reduced tumor uptake, showing tumor uptake to be receptor-mediated. To a lesser extent, this was also observed for the colon, but not for other tissues. We concluded that DTPA-(Pip)Gly-Pro-(PipAm)Gly-Arg-Pro-Tyr-tBuGly-Leu-OH and the DOTA-linked counterpart have the most favorable biodistribution properties regarding tumor uptake. |
| Databáze: | OpenAIRE |
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