Abstract
The Auger electron emitting agent 5-[125I]iodo-2′-deoxyuridine (i.e.[125I]IUdR) holds promise for the treatment of residual glioma after surgery because this thymidine analogue kills only proliferating cells. However, malignant cells which are not synthesizing DNA during exposure to the radiopharmaceutical will be spared. To determine whether tumour incorporation of [125I]IUdR could be enhanced by protracted administration, we used a C6 cell line, growing in the brains of Wistar rats, as a glioma model and compared three methods of intracerebral delivery of [125I]IUdR. Twenty-four hours after administration of drug, autoradiography of brain sections demonstrated nuclear uptake of the radiopharmaceutical in cells throughout tumour while normal brain cells remained free of radioactivity. The [125I]IUdR labelling indices (% ± s.e.m.) achieved were 6.2 (0.4) by single injection, 22.5 (4.1) using a sustained release polymer implant (poly(lactide-co-glycolide)) and 34.3 (2.0) by mini-osmotic pump. These results emphasize the need for a sustained delivery system as a prerequisite for effective treatment. These findings are also encouraging for the development of a sustained release system for radiolabelled IUdR for use in the treatment of intracranial tumours, particularly in the immediate postoperative setting. © 2000 Cancer Research Campaign
Keywords: radioiododeoxyuridine, glioma, intracerebral therapy, rat, sustained release
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- Baranowska-Kortylewicz J., Makrigiorgos G. M., Van den Abbeele A. D., Berman R. M., Adelstein S. J., Kassis A. I. 5-[123I]iodo-2'-deoxyuridine in the radiotherapy of an early ascites tumor model. Int J Radiat Oncol Biol Phys. 1991 Nov;21(6):1541–1551. doi: 10.1016/0360-3016(91)90331-w. [DOI] [PubMed] [Google Scholar]
- Beutler A. S., Banck M. S., Wedekind D., Hedrich H. J. Tumor gene therapy made easy: allogeneic major histocompatibility complex in the C6 rat glioma model. Hum Gene Ther. 1999 Jan 1;10(1):95–101. doi: 10.1089/10430349950019228. [DOI] [PubMed] [Google Scholar]
- Brem H., Piantadosi S., Burger P. C., Walker M., Selker R., Vick N. A., Black K., Sisti M., Brem S., Mohr G. Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-brain Tumor Treatment Group. Lancet. 1995 Apr 22;345(8956):1008–1012. doi: 10.1016/s0140-6736(95)90755-6. [DOI] [PubMed] [Google Scholar]
- Cunningham S. H., Mairs R. J., Wheldon T. E., Welsh P. C., Vaidyanathan G., Zalutsky M. R. Toxicity to neuroblastoma cells and spheroids of benzylguanidine conjugated to radionuclides with short-range emissions. Br J Cancer. 1998 Jun;77(12):2061–2068. doi: 10.1038/bjc.1998.348. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kassis A. I., Adelstein S. J. 5-[125]iodo-2'-deoxyuridine in the radiotherapy of solid CNS tumors in rats. Acta Oncol. 1996;35(7):935–939. doi: 10.3109/02841869609104048. [DOI] [PubMed] [Google Scholar]
- Kassis A. I., Fayad F., Kinsey B. M., Sastry K. S., Taube R. A., Adelstein S. J. Radiotoxicity of 125I in mammalian cells. Radiat Res. 1987 Aug;111(2):305–318. [PubMed] [Google Scholar]
- Kassis A. I., Tumeh S. S., Wen P. Y., Baranowska-Kortylewicz J., Van den Abbeele A. D., Zimmerman R. E., Carvalho P. A., Garada B. M., DeSisto W. C., Bailey N. O. Intratumoral administration of 5-[123I]iodo-2'-deoxyuridine in a patient with a brain tumor. J Nucl Med. 1996 Apr;37(4 Suppl):19S–22S. [PubMed] [Google Scholar]
- Kassis A. I., Wen P. Y., Van den Abbeele A. D., Baranowska-Kortylewicz J., Makrigiorgos G. M., Metz K. R., Matalka K. Z., Cook C. U., Sahu S. K., Black P. M. 5-[125I]iodo-2'-deoxyuridine in the radiotherapy of brain tumors in rats. J Nucl Med. 1998 Jul;39(7):1148–1154. [PubMed] [Google Scholar]
- Klecker R. W., Jr, Jenkins J. F., Kinsella T. J., Fine R. L., Strong J. M., Collins J. M. Clinical pharmacology of 5-iodo-2'-deoxyuridine and 5-iodouracil and endogenous pyrimidine modulation. Clin Pharmacol Ther. 1985 Jul;38(1):45–51. doi: 10.1038/clpt.1985.132. [DOI] [PubMed] [Google Scholar]
- Larsen R. H., Vaidyanathan G., Zalutsky M. R. Cytotoxicity of alpha-particle-emitting 5-[211At]astato-2'-deoxyuridine in human cancer cells. Int J Radiat Biol. 1997 Jul;72(1):79–90. doi: 10.1080/095530097143563. [DOI] [PubMed] [Google Scholar]
- Martin R. F., Haseltine W. A. Range of radiochemical damage to DNA with decay of iodine-125. Science. 1981 Aug 21;213(4510):896–898. doi: 10.1126/science.7256283. [DOI] [PubMed] [Google Scholar]
- Menei P., Boisdron-Celle M., Croué A., Guy G., Benoit J. P. Effect of stereotactic implantation of biodegradable 5-fluorouracil-loaded microspheres in healthy and C6 glioma-bearing rats. Neurosurgery. 1996 Jul;39(1):117–124. doi: 10.1097/00006123-199607000-00023. [DOI] [PubMed] [Google Scholar]
- Neshasteh-Riz A., Angerson W. J., Reeves J. R., Smith G., Rampling R., Mairs R. J. Incorporation of iododeoxyuridine in multicellular glioma spheroids: implications for DNA-targeted radiotherapy using Auger electron emitters. Br J Cancer. 1997;75(4):493–499. doi: 10.1038/bjc.1997.86. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neshasteh-Riz A., Mairs R. J., Angerson W. J., Stanton P. D., Reeves J. R., Rampling R., Owens J., Wheldon T. E. Differential cytotoxicity of [123I]IUdR, [125I]IUdR and [131I]IUdR to human glioma cells in monolayer or spheroid culture: effect of proliferative heterogeneity and radiation cross-fire. Br J Cancer. 1998;77(3):385–390. doi: 10.1038/bjc.1998.61. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Donoghue J. A., Wheldon T. E. Targeted radiotherapy using Auger electron emitters. Phys Med Biol. 1996 Oct;41(10):1973–1992. doi: 10.1088/0031-9155/41/10/009. [DOI] [PubMed] [Google Scholar]
- Olivi A., Ewend M. G., Utsuki T., Tyler B., Domb A. J., Brat D. J., Brem H. Interstitial delivery of carboplatin via biodegradable polymers is effective against experimental glioma in the rat. Cancer Chemother Pharmacol. 1996;39(1-2):90–96. doi: 10.1007/s002800050542. [DOI] [PubMed] [Google Scholar]
- Reza M. S., Whateley T. L. Iodo-2'-deoxyuridine (IUdR) and 125IUdR loaded biodegradable microspheres for controlled delivery to the brain. J Microencapsul. 1998 Nov-Dec;15(6):789–801. doi: 10.3109/02652049809008261. [DOI] [PubMed] [Google Scholar]
- Sahu S. K., Wen P. Y., Foulon C. F., Nagel J. S., Black P. M., Adelstein S. J., Kassis A. I. Intrathecal 5-[125I]iodo-2'-deoxyuridine in a rat model of leptomeningeal metastases. J Nucl Med. 1997 Mar;38(3):386–390. [PubMed] [Google Scholar]
- Sipos E. P., Tyler B., Piantadosi S., Burger P. C., Brem H. Optimizing interstitial delivery of BCNU from controlled release polymers for the treatment of brain tumors. Cancer Chemother Pharmacol. 1997;39(5):383–389. doi: 10.1007/s002800050588. [DOI] [PubMed] [Google Scholar]
- Vaidyanathan G., Larsen R. H., Zalutsky M. R. 5-[211 At]astato-2'-deoxyuridine, an alpha particle-emitting endoradiotherapeutic agent undergoing DNA incorporation. Cancer Res. 1996 Mar 15;56(6):1204–1209. [PubMed] [Google Scholar]
- Vertosick F. T., Jr, Selker R. G., Grossman S. J., Joyce J. M. Correlation of thallium-201 single photon emission computed tomography and survival after treatment failure in patients with glioblastoma multiforme. Neurosurgery. 1994 Mar;34(3):396–401. doi: 10.1227/00006123-199403000-00002. [DOI] [PubMed] [Google Scholar]
- Walicka M. A., Vaidyanathan G., Zalutsky M. R., Adelstein S. J., Kassis A. I. Survival and DNA damage in Chinese hamster V79 cells exposed to alpha particles emitted by DNA-incorporated astatine-211. Radiat Res. 1998 Sep;150(3):263–268. [PubMed] [Google Scholar]
- Williams J. A., Dillehay L. E., Tabassi K., Sipos E., Fahlman C., Brem H. Implantable biodegradable polymers for IUdR radiosensitization of experimental human malignant glioma. J Neurooncol. 1997 May;32(3):181–192. doi: 10.1023/a:1005704913330. [DOI] [PubMed] [Google Scholar]
- Zhu J., Zhang L., Hanisch U. K., Felgner P. L., Reszka R. A continuous intracerebral gene delivery system for in vivo liposome-mediated gene therapy. Gene Ther. 1996 Jun;3(6):472–476. [PubMed] [Google Scholar]