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

Abstract

Purpose It has been shown that some primary human tumours and their metastases, including prostate and breast tumours, overexpress gastrin-releasing peptide (GRP) (5-14)), was tested in vivo in biodistribution studies using rats bearing GRP receptor-expressing CA20948 tumours, and nude mice bearing human PC3 xenografts. Injection of 111In-labelled Cmp 3 in these animals showed high, receptor-mediated uptake in receptor-positive organs and tumours which could be visualised using planar gamma camera and microSPECT/CT imaging. Conclusion With their enhanced receptor affinity and their rapid receptor-mediated internalisation in vitro and in vivo, the new BN analogues, and especially Cmp 3, are promising candidates for use in diagnostic molecular imaging and targeted radionuclide therapy of GRP receptor-expressing cancers.

Bombesin-related peptides and their receptors: recent advances in their role in physiology and disease states

“…Therefore the development of labeled Bn analogues for imaging or targeted cytotoxicity is a very active area of investigation at present. Numerous radiolabeled [ 111 Indium, 68 Gallium, 177 Lutetium, 64 Copper, 86 Yttrium, 18 F, 99m Tc] GRP analogues with enhanced stability that bind with high affinity to BB 2 -receptors are reported, as well as there ability to image various human tumors in vivo using gamma detectors or PET imaging [10,[69][70][71][72][73][74][75][76][77]. In some preliminary studies in humans, tumors were imaged in the majority of patients, and in some cases, tumors were detected using radiolabeled Bn analogues that were not seen on other commonly used imaging modalities [75,[78][79][80].…”

“…Bn has relatively high affinity for both the BB 1 -receptor and the BB 2 -receptor, therefore many of the older pharmacological studies, both in vitro and in vivo, which usually used Bn as the agonist, provide limited information about the subtype of Bn receptor involved [3••]. Whereas BB 3 -receptor has low affinity for all natural occurring Bn-related peptides, a synthetic Bn ligand, [D-Tyr 6 , β-Ala 11 , Phe 13 , Nle 14 ] bombesin [6][7][8][9][10][11][12][13][14] , has been described [7] which has high affinity for the human and monkey BB 3 -receptor and this peptide or its analogues are being widely used to study the presence of the BB 3 -receptor, as well as other Bn receptors in human tissues by autoradiographic methods [8,9,10•]. This synthetic peptide has the unique property of having high affinity also for the BB 1 -receptor and BB 2 -receptor from all species.…”

“…Because there are no specific antagonists to this receptor, the synthetic agonist, [D-Tyr 6 , β-Ala 11 , Phe 13 , Nle 14 ] bombesin [6][7][8][9][10][11][12][13][14], is a nonselective agonist for this receptor and the natural ligand is unknown, the clues to its possible role in physiological and pathological processes have come from studies of BB 3 -receptor knockout mice or from proposals from localization studies of the receptor [3••]. The initial study of BB 3 -receptor knockout mice [42] reported the mice had mild obesity, hypertension and impairment in glucose metabolism, which were associated with increased feeding behavior and increased leptin levels.…”

PET of Tumors Expressing Gastrin-Releasing Peptide Receptor with an 18F-Labeled Bombesin Analog

“…In previous studies in PC-3-bearing mice, 67 Ga-PESIN, 177 Lu-AMBA, and 99m Tc-demobesin-1 showed tumor uptake of 14.8, 6.4, and 16.2 %ID/g, respectively (9,(25)(26)(27)(28). Variation in amounts of peptides, mouse strain (species, sex, and weight), tumor cells (passage number, culture conditions) used, tumor size, and vascularization of the tumor may all be factors that affect tumor uptake and tumor-to-non-tumor ratios.…”

Recent Development and Trends in Molecular Imaging Probes for Prostate Cancer

“…These data suggest that 123I-PD153035 are promising candidates as an imaging probe for EGFR-positive prostate cancer and warrant further in vivo validations to ascertain their potential as imaging agents for clinical used. Another radiolabeled bombesin (a target molecular with high affinity for GRP receptors) analogues was synthesized and assessed for SPECT (111In label) and PET (64Cu or 18F label) visualization of prostate cancer [58,59]. However, imaging of the GRP receptor is being under the further investigation to determine whether it is useful or not in clinical trial for prostate cancer.…”