Synthesis and Evaluation of Bombesin Derivatives on the Basis of Pan-Bombesin Peptides Labeled with Indium-111, Lutetium-177, and Yttrium-90 for Targeting Bombesin Receptor-Expressing Tumors

Abstract

ABSTRACT

Novel 111In-labelled bombesin analogues for molecular imaging of prostate tumours

“…These ratios compare well with those reported for other radiolabelled BN analogues in the literature [26-31, 36, 40]. For example, the recently published 111 In-BZH1 and 111 In-BZH2 showed tumour-to-muscle ratios in AR42J tumourbearing rats of 171 and 99 respectively, compared with 146 for 111 In-Cmp 3 at 4 h post injection [26]. This study shows that shortening the amino acid sequence and replacing specific amino acids in the BN sequence can yield compounds with improved receptor affinity ( Table 1).…”

“…For example, 99m Tcand 111 In-coupled BN analogues have been developed for diagnostic SPECT imaging and 64 Cu-and 68 Ga-labelled analogues for PET imaging of GRP receptor-expressing tumours [26][27][28][29][30][31][32][33][34][35][36][37][38][39]. In addition, 90 Y-and 177 Lu-labelled analogues have been described as promising tools for targeted radiotherapy of these tumours [26,40].…”

Molecular Imaging of Breast Cancer Tissue via Site-Directed Radiopharmaceuticals

“…Radiopharmaceuticals designed to target the GRPr employ modified analogs of bombesin, a tetradecapeptide initially isolated from the skin of the fire-bellied toad Bombina bombina in 1971 (Reubi, 2008;Zhang et al, 2004). The amidated C-terminus sequence of seven amino acids (Trp-Ala-Val-Gly-His-Leu-Met-NH 2 ), which is homologous to that of GRP (Table 3), is utilized for conjugate synthesis as a result of the fact that this sequence is sufficient for specific high affinity binding to the GRPr.…”

“…In the case of BBN(8-14)NH 2 based analogs, the incorporation of a tethering moiety between the receptor binding sequence and the radiometal complex influences not only the pharmacokinetic properties and renal retention of the resulting conjugate, but also the binding affinity and the degree of receptor-mediated analog uptake that is observed in GRPr rich tissues. In order to maintain a GRPr binding affinity that is similar to native BBN, the receptor binding sequence and the radiometal chelate must be separated by a distance of five or more atoms and the spacer sequence employed to serve this purpose must not introduce an extra negative charge at the N-terminus (Hoffman et al, 2001;Zhang et al, 2004). Additionally, a spacer group creates distance between the appended radiometal chelate and the receptor binding sequence, which promotes the biological integrity of the radiotracer (Pomper & Gelovani, 2008).…”

Estudo da marcação com lutécio-177 de derivados da bombesina e avaliação das propriedades biológicas

“…Estudos prévios descrevem que a radiomarcação de peptídeos quelados ao DTPA, com 67 Ga e 177 Lu, pode ser realizada à temperatura ambiente sem prejuízo para a pureza radioquímica (ZHANG et al, 2004). Entretanto, na marcação do derivado de bombesina conjugado ao DTPA, a marcação à temperatura ambiente apresenta grande variação no rendimento de marcação, com valores médio em torno de 80% de pureza radioquímica.…”