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Androgen-Dependent Expression of the Gastrin-Releasing Peptide Receptor in Human Prostate Tumor Xenografts

¹ Department of Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands; and ² Experimental Urology, Erasmus MC, Rotterdam, The Netherlands

Correspondence: For correspondence or reprints contact: Monique de Visser, Bachelor, Department of Nuclear Medicine, Erasmus MC, Room L-208, Dr. Molewaterplein 40, 3015GD Rotterdam, The Netherlands. E-mail: m.devisser{at}erasmusmc.nl

Human prostate cancers (PC) overexpress gastrin-releasing peptide (GRP) receptors. This observation suggests that GRP receptors may be used as new visualization and treatment modalities for these tumors. Radiolabeled GRP receptor-targeting analogs of GRP and bombesin (BN) have successfully been developed for these purposes. Expression of GRP receptors in human prostate tumors is, however, primarily evaluated in early stages of tumor development and information on expression in the more progressive prostate tumors is uncertain. To evaluate GRP receptor expression in all stages of PC, we investigated GRP receptor expression using a panel of 12 established human PC xenograft models representing the different stages of human PC and the effect of antiandrogen treatment (castration). Methods: Human PC xenografts were grown in male nude mice, and GRP receptor density in the tumors was evaluated using displacement receptor autoradiography with the universal BN receptor analog ¹²⁵I-[D-Tyr⁶,ß-Ala¹¹,Phe¹³,Nle¹⁴]BN(6–14) and the BN analog ¹¹¹In-[DTPA-Pro¹,Tyr⁴]BN (DTPA is diethylenetriaminepentaacetic acid) before and after castration. Results: Autoradiography showed high-density GRP receptor expression in the androgen-dependent tumors (3/12 models), whereas only very low receptor expression was found in the androgen-responsive and -independent tumors (9/12 models). Castration resulted in GRP receptor downregulation (11%–36% of initial values) in the 3 androgen-dependent tumors. Conclusion: High GRP receptor density was only observed in androgen–dependent PC xenografts, indicating high GRP receptor expression in the early, androgen-dependent, stages of prostate tumor development and not in later stages. In addition, castration strongly reduced GRP receptor expression in androgen-dependent tumors, indicating that GRP receptor expression in human PC is androgen-regulated.

Key Words: androgen regulation • prostate cancer • bombesin • gastrin-releasing peptide receptor • xenografts

COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.

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