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European Journal of Nuclear Medicine and Molecular Imaging

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Open Access 01-07-2010 | Original Article

A standardised study to compare prostate cancer targeting efficacy of five radiolabelled bombesin analogues

Authors: Rogier P. J. Schroeder, Cristina Müller, Suzanne Reneman, Marleen L. Melis, Wout A. P. Breeman, Erik de Blois, Chris H. Bangma, Eric P. Krenning, Wytske M. van Weerden, Marion de Jong

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 7/2010

Abstract

Purpose

Prostate-specific antigen (PSA)-based screening for prostate cancer (PC) has dramatically increased early diagnosis. Current imaging techniques are not optimal to stage early PC adequately. A promising alternative to PC imaging is peptide-based scintigraphy using radiolabelled bombesin (BN) analogues that bind to gastrin-releasing peptide receptors (GRPR) being overexpressed in PC. When labelled to appropriate radionuclides BN targeting of GRPRs may also provide applications for peptide radionuclide receptor therapy (PRRT). Assessment studies under identical experimental conditions allowing a reliable comparison of the potential of such analogues are lacking. This study was performed to evaluate and directly compare five promising radiolabelled BN analogues for their targeting efficacy for PC under standardised conditions.

Methods

The BN agonists [¹¹¹In]DOTA-PESIN, [¹¹¹In]AMBA, [¹¹¹In]MP2346 and [¹¹¹In]MP2653 and one antagonist [^99mTc]Demobesin-1 were evaluated in GRPR-overexpressing human PC-3 tumour-bearing mice to determine peptide stability in vivo, biodistribution and GRPR targeting potential by animal SPECT/CT imaging and ex vivo autoradiography.

Results

HPLC analysis of blood showed intact Demobesin-1 at 5 and 15 min after injection (64.1 ± 1.6% and 41.0 ± 01%, respectively) being much less for the other compounds. AMBA, the second most stable analogue, showed 36.1 ± 2.7% and 9.8 ± 1.1% intact peptide after 5 and 15 min. PC-3 tumour uptake at 1 h was comparable for Demobesin-1, AMBA, PESIN and MP2346 (3.0 ± 0.4, 2.7 ± 0.5, 2.3 ± 0.5 and 2.1 ± 0.9%ID/g, respectively), but very low for MP2653 (0.9 ± 0.2%ID/g). In addition, MP2346 showed undesirably high uptake in the kidneys (7.9 ± 1.9%ID/g) being significantly less for the other analogues. AMBA, MP2346 and PESIN revealed favourable increases in tumour to blood ratios over time while changes in tumour to kidney and pancreas ratios for Demobesin-1 from 1 to 24 h after injection were significantly better than for the other analogues. All analogues visualised PC-3 tumours by SPECT/CT and autoradiography.

Conclusion

In the present study the BN antagonist Demobesin-1 was the best performing analogue showing superior in vivo stability, highest tumour uptake and retention while pancreatic and renal clearance were rapid. PESIN and AMBA were the best GRP agonists with sufficient in vivo stabilities as well as high tumour uptake and retention. Based on these results all three analogues deserve further evaluation for clinical use in PC patients.

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Title: A standardised study to compare prostate cancer targeting efficacy of five radiolabelled bombesin analogues
Authors: Rogier P. J. Schroeder
Cristina Müller
Suzanne Reneman
Marleen L. Melis
Wout A. P. Breeman
Erik de Blois
Chris H. Bangma
Eric P. Krenning
Wytske M. van Weerden
Marion de Jong
Publication date: 01-07-2010
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 7/2010
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-010-1388-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

A standardised study to compare prostate cancer targeting efficacy of five radiolabelled bombesin analogues

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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