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

ABSTRACT

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 [HYNIC[0], D-Tyr[6], D-Trp[8]] - BN [6-14] NH[2] that could be easily labeled with[99m]Tc and evaluation of its potential as an imaging agent. Synthesis of the peptide amide was carried out onto Rink Amide MB HA [4-Methylbenzhydrylamine] resin. A bifunctional chelating agent [BFCA] was attached to the N terminal peptide in solid-phase. [99m]Tc labeling was performed by addition of sodium pertechnetate to solution that include [HYNIC[0], D-Tyr[6], D-Trp[8]] Bombesin [6-14] NH[2], tricine, ethylenediamine-N,N'-diaeetic acid [EDDA] and SnCl[2]. 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. [99m]Tc/tricine/EDDA-HYNIC[0], D-Tyr[6], D-Trp[8]] bombesin [6-14] NH[2] 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. In this study, labeling of this novel conjugate with [99m] Tc easily was performed using coligand. The prepared [99m]Tc-HYNIC-BN conjugate has promising characteristics for the diagnosis of malignant tumors