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

Publish Year: 1388
نوع سند: مقاله ژورنالی
زبان: English
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شناسه ملی سند علمی:

JR_IRJNM-17-1_003

تاریخ نمایه سازی: 27 فروردین 1399

Abstract:

  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.

Authors

Nourollah Sadeghzadeh

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

Mostafa Gandomkar

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

Mohammad Shafiee

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

Mohammad Mazidi

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