Phases IB and II multidose trial of gadolinium texaphyrin, a radiation sensitizer detectable at MR imaging: Preliminary results in brain metastases

PURPOSE: To evaluate magnetic resonance (MR) imaging results after administ ration of gadolinium texaphyrin, a tumor-selective radiation sensitizer tha t is detectable at MR imaging, and to determine an appropriate intravenous dose of gadolinium texaphyrin for repeated injections during radiation ther apy, the dose-limiting toxicity of reiterated doses of gadolinium texaphyri n, the maximal tolerated dose, the biolocalization of gadolinium texaphyrin las assessed at MR examinations), and the response to treatment. MATERIALS AND METHODS: Ten daily intravenous injections of gadolinium texap hyrin, each followed by whole-brain radiation therapy (total of 10 fraction s, 30 Gy), were administered to patients with brain metastases in a multice nter study. At the study institution, 11 patients underwent MR imaging befo re and after the first injection, after the 10th injection, and 8 weeks aft er entry into the study. RESULTS: MR imaging revealed selective drug uptake in metastases, without e nhancement of normal brain tissue. In 10 patients, tumor uptake was higher after the 10th injection than after the first injection, which indicated ac cumulation of gadolinium texaphyrin in metastases. One lesion was visible o nly after the 10th injection and not at the pretherapeutic MR examination w ith injection of conventional gadolinium-based contrast material. Response to treatment was defined as a reduction in the size of the metastases betwe en the preinjection MR study and the last MR study; seven patients achieved partial remission with tumor regression exceeding 50% of the initial size, and four achieved a minor response with less than; 50% tumor regression. CONCLUSION: These preliminary results indicate that gadolinium texaphyrin i s tumor selective and that brain metastases can be depicted at MR imaging l ong after the administration of gadolinium texaphyrin.