The noninvasive assessment of anticancer treatment efficacy is very important for the improvement of therapeutic window. The purpose of the present study was to evaluate the antitumoral effects of the vascular targeting agent, combretastatin A-4 phosphate (CA-4-P), at selected time points after repeated intraperitoneal drug administrations (25 mg/kg), using diffusion-weighted magnetic resonance imaging (DW-MRI). The experiments were performed during an overall follow-up period of 3 weeks on WAG/Rij rats with subcutaneously growing rhabdomyosarcomas. Each animal served as its own baseline. The DW-MRI studies were quantified by calculating the apparent diffusion coefficient (ADC) for different low and high b-values to separate the effects on tumor vasculature and cellular integrity. The changes in ADC as well as the extent of necrosis development (proportional to the tumor volume), measured on the MR images, were of comparable magnitude after each treatment. All ADC values showed a significant decrease at 6 hours, followed by a significant increase at 2 days for various CA-4-P administrations. DW-MRI allowed us to monitor both reduction in perfusion and changes in the extent of tumor necrosis after CA-4-P injection. Repeated CA-4-P administration retains efficacy in rat rhabdomyosarcomas, with similar findings after each drug administration.

Photodynamic therapy (PDT) involves the local or systemic administration of a photosensitizing drug that, upon light irradiation and presence of oxygen, results in tissue damage such as tumor destruction. Hypericin, a hydroxylated phenanthroperylenequinone, is obtained from Hypericum perforatum plants. Hypericin exhibits a high fluorescence quantum yield, and its presence in the tissue can easily be visualized. Interestingly, when instilled into the human bladders, hypericin selectively accumulates in the bladder carcinoma lesions, with the specificity and sensitivity of detecting CIS reaching up to 98.5 and 93%, respectively. Due to this selective accumulation of hypericin in bladder carcinoma lesions, the compound is now used as a fluorescent diagnostic tool for superficial bladder cancer. However, hypericin is also a photosensitizer with a potent photocytotoxic activity. Taken together, these data indicate that hypericin could be used for whole bladder wall PDT of superficial bladder tumors. This review focuses on the more recent in vitro and in vivo evaluation of hypericin as a photodynamic agent in the treatment of superficial transitional cell carcinoma (TCC) bladder tumors.

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