Evaluation of 111In-DTPA-Folate as a Receptor-Targeted Diagnostic Agent for Ovarian Cancer: Initial Clinical Results

The cell-membrane folate receptor is a potential molecular target for tumor-selective drug delivery, including radiolabeled folate-chelate conjugates for diagnostic imaging. We report here the initial clinical study of such an agent, (111)In-diethylenetriaminepentaacetic acid (DTPA)-folate, evaluated for diagnosis of ovarian malignancy. Thirty-five women were enrolled in a phase I/II clinical study, with 33 completing the surgical follow-up required by the study protocol for definition of disease status. Patients either had a pathologically proven malignancy or were scheduled for surgery for suspected new ovarian cancer (n = 26), recurrent ovarian cancer (n = 5), or endometrial cancer (n = 2). (111)In-DTPA-folate was administered as an intravenous bolus, and whole-body images were obtained at 30 min, 4 h, and (for the first 19 patients) 24 h after injection; SPECT also was done at the delayed imaging times. For 19 of the patients, unlabeled free folic acid was injected before administration of (111)In-DTPA-folate to also assess the impact of folate loading on tracer biodistribution. Masked and unmasked readings of the images by 2 nuclear medicine physicians were compared with the pathologic findings after surgery. Among 33 patients who had surgical intervention, 14 had new or recurrent malignant tumors. All of 7 newly diagnosed ovarian carcinomas were identified by both masked readers (sensitivity, 100%). The sensitivity for detection of 7 recurrent malignancies was 38% for masked readings and 85% for unmasked readings, indicating that correlation with anatomic imaging studies (CT) was highly important in diagnosis of these lesions. Eighteen of the studied patients were found to have benign masses; for this limited population, the specificity of (111)In-DTPA-folate scintigraphy was 76% and 82% for the masked and unmasked analyses, respectively. (111)In-DTPA-folate is safe, and possibly effective, for scintigraphy differentiating between malignant and benign ovarian masses.