Synthesis and evaluation of a new radiolabeled bombesin analogue for diagnosis of GRP receptor expressing tumors

Document Type: Original Article


1 Department of Nuclear Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

2 Nuclear Science Research School, Nuclear Science & Technology Research Institute (NSTRI), Atomic Energy Organization of Iran, Tehran, Iran

3 Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran


  Introduction: Bombesin (BN), a 14-amino acid neuropeptide, shows high affinity for the human GRP (gastrin releasing peptide) receptors, which are overexpressed by a variety of cancers, including prostate, breast, pancreas, gastrointestinal, and small cell lung cancer. Aim was to prepare [6-hydrazinopyridine-3-carboxylic acid (HYNIC0), D-Tyr6, D-Trp8] - BN [6-14] NH2 that could be easily labeled with 99mTc and evaluation of its potential as an imaging agent. Methods: Synthesis of the peptide amide was carried out onto Rink Amide MBHA (4-Methylbenzhydrylamine) resin. A bifunctional chelating agent (BFCA) was attached to the N terminal peptide in solid-phase. 99mTc labeling was performed by addition of sodium pertechnetate to solution that include [HYNIC0, D-Tyr6, D-Trp8] Bombesin [6-14] NH2, tricine, ethylenediamine-N,N′-diacetic acid (EDDA) and SnCl2. Radiochemical evaluation was carried out by reverse phase high-performance liquid chromatography (HPLC) and instant thin layer chromatography (ITLC). In-vitro internalization was tested using human prostate cancer cells (PC-3) with blocked and non-blocked receptors. Biodistribution was determined in rats. Results:[99mTc/tricine/EDDA-HYNIC0, D-Tyr6, D-Trp8] bombesin [6-14] NH2 was obtained with radiochemical purities >98%. Results of in-vitro studies demonstrated a high stability in serum and suitable internalization. Biodistribution data showed a rapid blood clearance, with renal excretion and specific binding towards GRP receptor-positive tissues such as pancreas. Conclusion: In this study, labeling of this novel conjugate with 99mTc easily was performed using coligand. The prepared 99mTc-HYNIC-BN conjugate has promising characteristics for the diagnosis of malignant tumors.


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