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: | Tesson, Dr Mathias and Mairs, Professor Robert and Nixon, Mr Colin and Rae, Dr Colin |
| Authors: | Tesson, M., Rae, C., Nixon, C., Babich, J. W., and Mairs, R. J. |
| College/School: | College of Medical Veterinary and Life Sciences > School 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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