Phases IB and II multidose trial of gadolinium texaphyrin, a radiation sensitizer detectable at MR imaging: preliminary results in brain metastases.
OBJECTIVE
To evaluate magnetic resonance (MR) imaging results after administration of gadolinium texaphyrin, a tumor-selective radiation sensitizer that is detectable at MR imaging, and to determine an appropriate intravenous dose of gadolinium texaphyrin for repeated injections during radiation therapy, the dose-limiting toxicity of reiterated doses of gadolinium texaphyrin, the maximal tolerated dose, the biolocalization of gadolinium texaphyrin (as assessed at MR examinations), and the response to treatment.


METHODS
Ten daily intravenous injections of gadolinium texaphyrin, each followed by whole-brain radiation therapy (total of 10 fractions, 30 Gy), were administered to patients with brain metastases in a multicenter study. At the study institution, 11 patients underwent MR imaging before and after the first injection, after the 10th injection, and 8 weeks after entry into the study.


RESULTS
MR imaging revealed selective drug uptake in metastases, without enhancement of normal brain tissue. In 10 patients, tumor uptake was higher after the 10th injection than after the first injection, which indicated accumulation of gadolinium texaphyrin in metastases. One lesion was visible only after the 10th injection and not at the pretherapeutic MR examination with injection of conventional gadolinium-based contrast material. Response to treatment was defined as a reduction in the size of the metastases between 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.


CONCLUSIONS
These preliminary results indicate that gadolinium texaphyrin is tumor selective and that brain metastases can be depicted at MR imaging long after the administration of gadolinium texaphyrin.
Viala
J
J
Department of Radiology, Institut Gustave-Roussy, Villejuif, France.
Vanel
D
D
Meingan
P
P
Lartigau
E
E
Carde
P
P
Renschler
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology / Q000528:radiation effects; D001932:Brain Neoplasms / Q000175:diagnosis / Q000532:radiotherapy / Q000556:secondary*; D003287:Contrast Media / Q000008:administration & dosage* / Q000009:adverse effects; D016371:Cranial Irradiation; D004305:Dose-Response Relationship, Drug; D005260:Female; D005682:Gadolinium / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D008665:Metalloporphyrins / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D010166:Palliative Care; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000009:adverse effects; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D003287:Contrast Media; D008665:Metalloporphyrins; D011838:Radiation-Sensitizing Agents; C437683:motexafin gadolinium; D005682:Gadolinium