Monitoring Pc 4-mediated photodynamic therapy of U87 tumors with dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) in the athymic nude rat

Davood Varghai M.D.; Kelly Covey; Rahul Sharma; Nathan Cross; Denise K. Feyes; Nancy L. Oleinick; Chris A. Flask; David Dean

doi:10.1117/12.763983

26 February 2008 Monitoring Pc 4-mediated photodynamic therapy of U87 tumors with dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) in the athymic nude rat

Davood Varghai M.D., Kelly Covey, Rahul Sharma, Nathan Cross, Denise K. Feyes, Nancy L. Oleinick, Chris A. Flask, David Dean

Author Affiliations +

Proceedings Volume 6842, Photonic Therapeutics and Diagnostics IV; 68422P (2008) https://doi.org/10.1117/12.763983
Event: SPIE BiOS, 2008, San Jose, California, United States

Abstract

Post-operative verification of the specificity and sensitivity of photodynamic therapy (PDT) is most pressing for deeply placed lesions such as brain tumors. We wish to determine whether Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) can provide a non-invasive and unambiguous quantitative measure of the specificity and sensitivity of brain tumor PDT. Methods: 2.5 x 10⁵ U87 cells were injected into the brains of six athymic nude rats. After 5-6 days, the animals received 0.5 mg/kg b.w. of the phthalocyanine photosensitizer Pc 4 via tail-vein injection. On day 7 peri-tumor DCE-MRI images were acquired on a 7T microMRI scanner before and after tail-vein administration of 100 μL gadolinium and 400 μL saline. After this scan the animals received a 30 J/cm² dose of 672-nm light from a diode laser (i.e., PDT). The DCE-MRI scan protocol was repeated on day 13. Next, the animals were euthanized and their brains were explanted for Hematoxylin and Eosin (H&E) histology. Results: No tumor was found in one animal. The DCE-MRI images of the other five animals demonstrated significant tumor enhancement increase (p < 0.053 two-sided t-test and p < 0.026 one-sided t-test) following PDT. H&E histology presented moderate to severe tumor necrosis. Discussion: The change in signal detected by DCE-MRI appears to be due to PDT-induced tumor necrosis. This DCE-MRI signal appears to provide a quantitative, non-invasive measure of the outcome of PDT in this animal model and may be useful for determining the safety and effectiveness of PDT in deeply placed tumors (e.g., glioma).

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Davood Varghai M.D., Kelly Covey, Rahul Sharma, Nathan Cross, Denise K. Feyes, Nancy L. Oleinick, Chris A. Flask, and David Dean "Monitoring Pc 4-mediated photodynamic therapy of U87 tumors with dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) in the athymic nude rat", Proc. SPIE 6842, Photonic Therapeutics and Diagnostics IV, 68422P (26 February 2008); https://doi.org/10.1117/12.763983

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