Evaluation of a new radiolabeled bombesin derivative with 99mTc as potential targeted tumor imaging agent

Abstract

Gastrin-releasing peptide (GRP) receptors are over-expressed in various human tumor including breast and prostate which can be targeted with bombesin for diagnosis and targeted therapy. High abdominal accumulation and the poor in vivo stability of radiolabeled bombesin analogues may represent a limitation for diagnostic imaging and targeted therapy. In this study a new bombesin derivative was labeled with ^99mTc via HYNIC and tricine as a coligand and investigated further. The peptide HYNIC conjugate was synthesized on a solid phase using Fmoc strategy. Labeling with ^99mTc was performed at 100 °C for 10 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. Internalization was studied with the human GRP receptor cell line PC-3. The Biodistribution was studied in mice. Labeling yield of >98 % was obtained to correspond a specific activity of ~80.9 GBq/μmol. Radioconjugate internalization into PC-3 cells was high and specific (15.6 ± 1.9 % at 4 h). A high and specific uptake in GRP-receptor-positive organs such as mouse tumor and pancreas (2.11 ± 0.18 and 1.78 ± 0.09 % ID/g after 1 h respectively) was also determined.

Keywords: 99mTc; Bombesin; GRP; Radiopeptide; Tumor.

Fig. 1

Structure of [HYNIC-d-Tyr⁵-d-Tyr⁶-d-Phe¹³] BB (5–14)

Fig. 2

RP-HPLC profile of [^99mTc/tricine/HYNIC⁰, d-Tyr⁵- d-Tyr⁶-d-Phe¹³] Bombesin (5–14)

Fig. 3

Time course internalization of [^99mTc/tricine/HYNIC⁰, d-Tyr⁵-d-Tyr⁶-d-Phe¹³] bombesin (5–14) in unblocked and blocked PC-3 cells. Result of three independent experiments with triplicates in each experiment

Fig. 4

Biodistribution findings in mice (% injected dose per gram organ ± SD, n = 3)