Novel 111In-labelled bombesin analogues for molecular imaging of prostate tumoursReportar como inadecuado

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European Journal of Nuclear Medicine and Molecular Imaging

, Volume 34, Issue 8, pp 1228–1238

First Online: 08 February 2007Received: 11 November 2005Accepted: 03 December 2006


PurposeIt has been shown that some primary human tumours and their metastases, including prostate and breast tumours, overexpress gastrin-releasing peptide GRP receptors. Bombesin BN is a neuropeptide with a high affinity for these GRP receptors. We demonstrated successful scintigraphic visualisation of BN receptor-positive tumours in preclinical studies using the radiolabelled BN analogue In-DTPA-Pro,TyrBN. However, the receptor affinity as well as the serum stability of this analogue leave room for improvement. Therefore new In-labelled BN analogues were synthesised and evaluated in vitro and in vivo.

Methods and resultsThe receptor affinity of the new BN analogues was tested on human GRP receptor-expressing prostate tumour xenografts and rat colon sections. Analogues with high receptor affinity low nM range were selected for further evaluation. Incubation in vitro of GRP receptor-expressing rat CA20948 and human PC3 tumour cells with the In-labelled analogues resulted in rapid receptor-mediated uptake and internalisation. The BN analogue with the best receptor affinity and in vitro internalisation characteristics, Cmp 3 In-DTPA-ACMpip,Tha,βAla,Tha,NleBN5–14, was tested in vivo in biodistribution studies using rats bearing GRP receptor-expressing CA20948 tumours, and nude mice bearing human PC3 xenografts. Injection of In-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.

ConclusionWith 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.

KeywordsBiodistribution Prostate cancer Molecular imaging Gastrin-releasing peptide receptor Bombesin analogues  Download fulltext PDF

Autor: M. de Visser - H. F. Bernard - J. L. Erion - M. A. Schmidt - A. Srinivasan - B. Waser - J. C. Reubi - E. P. Krenning


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