Quantitative MRI of Gd-DTPA uptake in tumors: response to photodynamic therapy

A partial saturation method is described for obtaining rapid images of tissue 1H spin-lattice relaxation rates following administration of the paramagnetic contrast agent gadolinium-diethylenetriaminepentaacetate. The paramagnetic contribution to the relaxation rates is proportional to the concentration of contrast agent, making possible quantitative studies of paramagnetic contrast agent uptake or vessel leakage. Snapshot imaging capabilities are not required. Maps of contrast agent uptake rates are made in rat borne tumors before and following photodynamic therapy, which is known to cause vascular damage. Uptake efficiency is spatially heterogeneous before and after therapy. Decreases in uptake rate are observed after two photo-irradiation protocols, which differ by a factor of four in fluence rate but deliver the same total fluence. There is no apparent fluence rate dependence for changes in the uptake rates within 5 h after therapy. Whole tumor measurements of nucleotide triphosphates, inorganic phosphate, pH, and lactate made with NMR spectroscopy indicate that, while net ATP production is inhibited, lactate concentrations are not strongly affected by photodynamic therapy. The ratio of nucleotide triphosphates to inorganic phosphate falls to 0.21 +/- 0.02 of initial values 5 h after tumors are treated with the lower fluence rate protocol, and falls to 0.40 +/- 0.06 in tumors treated with the higher fluence rate.