QUANTITATIVE MRI OF GD-DTPA UPTAKE IN TUMORS - RESPONSE TO PHOTODYNAMIC THERAPY

A partial saturation method is described for obtaining rapid images of tissue H-1 spin-lattice relaxation rates following administration of the paramagnetic contrast agent gadolinium-diethylenetriaminepentaacet ate. The paramagnetic contribution to the relaxation rates is proporti onal to the concentration of contrast agent, making possible quantitat ive studies of paramagnetic contrast agent uptake or vessel leakage. S napshot imaging capabilities are not required. Maps of contrast agent uptake rates are made in rat borne tumors before and following photody namic therapy, which is known to cause vascular damage. Uptake efficie ncy is spatially heterogenous before and after therapy. Decreases in u ptake rate are observed after two photo-irradiation protocols, which d iffer by a factor of four in fluence rate but deliver the same total f luence. There is no apparent fluence rate dependence for changes in th e uptake rates within 5 h after therapy. Whole tumor measurements of n ucleotide triphosphates, inorganic phosphate, pH, and lactate made wit h NMR spectroscopy indicate that, while net ATP production is inhibite d, lactate concentrations are not strongly affected by photodynamic th erapy. The ratio of nucleotide triphosphates to inorganic phosphate fa lls to 0.21 +/- 0.02 of initial values 5 h after tumors are treated wi th the lower fluence rate protocol, and falls to 0.40 +/- 0.06 in tumo rs treated with the higher fluence rate.