A lyophilized peptide radiopharmaceutical kit to target neurotensin receptor for tumor imaging

Abstract

Introduction: Neurotensin (NT) is a tridecapeptide that binds specifically to neurotensin receptors. Several forms of cancer, including small cell lung cancer, colon, pancreatic and prostate carcinomas especially exocrine pancreatic carcinomas express receptors for neurotensin peptide. Radiolabeled neurotensin derivatives with a high affinity for these receptors might be used for scintigraphy. The aim of this work was to prepare a freeze-dried kit formulation for routine preparation of 99mTc labeled neurotensin in nuclear medicine center. Methods: A freeze dried kit containing reducing agent, coligands and HYNIC-Neurotensin derivative for labeling with 99mTc was prepared. Labeling was performed at 95°C for 15 min and radiochemical analysis involved ITLC and HPLC methods. The stability of radiopeptide was checked in the presence of human serum at 37°C up to 24 h. The receptor bound internalization rate was studied in neurotensin receptor expressing HT-29 cells. Biodistribution of radiopeptide was studied in mice. Results: Labeling yield of >95% was obtained corresponding to a specific activity of 80 MBq/nmol. Prepared radioconjugate was stable in human serum and more than 12% of activity was specifically internalized into HT-29 cells up to 4 h. Biodistribution study showed a rapid blood clearance, with renal excretion and specific binding towards NT receptor-positive tissues such as intestines (0.99 ± 0.16% ID/g at 1 h). Conclusion: The favorable characteristics of our new designed labeled peptide formulation make it as a promising candidate for diagnosis of malignant tumors.