Diltiazem enhances tumor blood flow: MRI study in a murine tumor

Muruganandham, M. ; Kasiviswanathan, A. ; Jagannathan, N. R. ; Raghunathan, P. ; Jain, P. C. ; Jain, V. ; Nat, Phil (1999) Diltiazem enhances tumor blood flow: MRI study in a murine tumor International Journal of Radiation Oncology, Biology, Physics, 43 (2). pp. 413-421. ISSN 0360-3016

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Official URL: http://www.sciencedirect.com/science/article/pii/S...

Related URL: http://dx.doi.org/10.1016/S0360-3016(98)00403-9


Purpose: Diltiazem, a calcium-channel blocker, is known to differentially influence the radiation responses of normal and murine tumor tissues. To elucidate the underlying mechanisms, the effects of diltiazem on the radiation response of Ehrlich ascites tumor (EAT) in mice have been investigated, and the hemodynamic changes induced by diltiazem in tumor and normal muscle have been studied using magnetic resonance imaging (MRI) techniques. Methods and Materials: Ehrlich ascites tumors were grown subcutaneously in Swiss albino strain A mice. Dynamic gadodiamide and blood oxygen level dependent (BOLD) contrast enhanced 1H MR imaging studies of EAT and normal muscle were performed after administration of diltiazem in mice using a 4.7 Tesla MR scanner. Tumor radiotherapy experiments (total dose = 10 Gy, 0.4-0.5 Gy/min, single fraction) were carried out with 30 min preadministration of diltiazem (27.5 or 55 mg/kg i.p.) to EAT-bearing mice using a teletherapy machine. Results: The diltiazem+ radiation treated group showed significant tumor regression (in ~65% of the animals) and enhanced animal survival. MR-gadodiamide contrast kinetics revealed a higher magnitude of signal enhancement in diltiazem treated groups as compared to the controls. The observed changes in the magnitude of kinetic parameters were the same for both tumor and normal muscle. BOLD-MR images at 30 min after diltiazem administration showed a 25% and 8% (average) intensity enhancement from their basal values in tumor and normal muscle regions, respectively. The control group showed no significant changes. Conclusion: The present studies demonstrate the radiosensitization potential of diltiazem in the mice EAT model. The enhanced radiation response observed with diltiazem correlates with the diltiazem-induced increase in tumor blood flow (TBF) and tumor oxygenation. The present results also demonstrate the applications of BOLD-MR measurements in investigating the alterations in tumor oxygenation status.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
Keywords:Radiosensitization; Diltiazem; Vasomodulators; Oxygenation; Blood Flow; Tumor; MRI
ID Code:65864
Deposited On:19 Oct 2011 14:27
Last Modified:19 Oct 2011 14:27

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