BOLD contrast MR monitors antivascular photodynamic therapy in lab mice


CONTEXT: A blood oxygen level-dependent (BOLD) contrast MR study conducted by Dr. Yoram Salomon with Dr. Avigdor Scherz and Michal Neeman at the Weizmann Institute of Science in Rehovot, Israel was aimed at online follow-up of vascular targeting photodynamic therapy (PDT). This type of PDT was enabled by Tookad, a member of a new family of bacteriochlorophyll-based photodynamic sensitizers. It was invented by Scherz and developed with Steba Biotech and Negma-Lerads in France. Scherz and Salomon have shown that photosensitization of Tookad by fiber-optic-guided transcutaneous illumination shortly after intravenous injection results in oxidative tumor vascular damage and depletion of oxygen, leading to termination of blood supply and tumor eradication.

RESULTS: Mice were implanted with subcutaneous mouse melanoma. In the control groups, tumors grew in the four mice receiving Tookad without illumination and in four mice receiving illumination without Tookad. All six mice treated with PDT were tumor-free 90 days after treatment. BOLD MR images were acquired before, during, and after PDT every two minutes for 20 minutes with a 4.7T Bruker BioSpec spectrometer. Results suggest that light-induced photochemical oxygen depletion and vascular shutdown can be viewed with functional MRI. The principle was validated in the test tube on isolated human blood treated with Tookad and light under controlled experimental conditions.

IMAGE: Experimental setup (left) includes illumination of the tumor using optic fiber during intravenous administration of the drug inside the magnet bore. Sequential images acquired before (right top) and during (right middle and bottom) PDT enable Tookad shows decrease in MR signal intensity only in the illuminated regions.

IMPLICATIONS: Light-driven BOLD contrast MR could offer accurate monitoring for PDT of prostate, lung, brain, and other cancers. Tookad is in clinical trials for prostate cancer treatment in Canada, France, England, and Israel. U.S. testing may begin in 2004.

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