Preliminary evaluation of prostate-targeted radiotherapy using 131I-MIP-1095 in combination with radiosensitising chemotherapeutic drugs

Tesson, M., Rae, C. , Nixon, C., Babich, J. W. and Mairs, R. J. (2016) Preliminary evaluation of prostate-targeted radiotherapy using 131I-MIP-1095 in combination with radiosensitising chemotherapeutic drugs. Journal of Pharmacy and Pharmacology, 68(7), pp. 912-921. (doi:10.1111/jphp.12558) (PMID:27139157) (PMCID:PMC5298040)

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Abstract

Objectives Despite recent advances in the treatment of metastatic prostate can- cer, survival rates are low and treatment options are limited to chemotherapy and hormonal therapy. 131I-MIP-1095 is a recently developed prostate-specific membrane antigen (PSMA)-targeting, small molecular weight radiopharmaceuti- cal which has anti-tumour activity as a single agent. Our purpose was to deter- mine in vitro the potential benefit to be gained by combining 131I-MIP-1095 with cytotoxic drug treatments. Methods Various cytotoxic agents were evaluated in combination with 131I- MIP-1095 for their capacity to delay the growth of LNCaP cells cultured as multicellular tumour spheroids. Two end-points were used to assess treatment efficacy: (i) the time required for doubling of spheroid volume and (ii) the area under the volume–time growth curves. Key findings The PARP-1 inhibitor olaparib, the topoisomerase I inhibitor topotecan, the proteasome inhibitor bortezomib, the inhibitor of the P53– MDM2 interaction nutlin-3 and the copper-chelated form of the oxidising agent disulfiram (DSF:Cu) all significantly enhanced the inhibition of the growth of spheroids induced by 131I-MIP-1095. However, the Chk1 inhibitor AZD7762 failed to potentiate the effect of 131I-MIP-1095. Conclusions These results indicate that targeted radiotherapy of prostate cancer may be optimised by combining its administration with chemotherapy.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Nixon, Mr Colin and Rae, Dr Colin and Tesson, Dr Mathias and Mairs, Professor Robert
Authors: Tesson, M., Rae, C., Nixon, C., Babich, J. W., and Mairs, R. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Journal of Pharmacy and Pharmacology
Publisher:Wiley
ISSN:0022-3573
ISSN (Online):2042-7158
Published Online:03 May 2016
Copyright Holders:Copyright © 2016 Royal Pharmaceutical Society
First Published:First published in Journal of Pharmacy and Pharmacology 68(7):912-921
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
647981CR-UK Centre renewalKaren VousdenCancer Research UK (CAN-RES-UK)C596/A18076RI CANCER SCIENCES