Evaluation of 111In-DTPA-folate as a receptor-targeted diagnostic agent for ovarian cancer: Initial clinical results

Barry A. Siegel, Farrokh Dehdashti, David G. Mutch, Donald A. Podoloff, Richard Wendt, Gregory P. Sutton, Robert W. Burt, P. Ron Ellis, Carla J. Mathias, Mark A. Green, David M. Gershenson

Research output: Contribution to journalArticlepeer-review

131 Scopus citations

Abstract

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, 111In-diethylene-triaminepentaacetic acid (DTPA)-folate, evaluated for diagnosis of ovarian malignancy. Methods: 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). 111In-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 111In-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. Results: 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 111In-DTPA- folate scintigraphy was 76% and 82% for the masked and unmasked analyses, respectively. Conclusion: 111In-DTPA-folate is safe, and possibly effective, for scintigraphy differentiating between malignant and benign ovarian masses.

Original languageEnglish (US)
Pages (from-to)700-707
Number of pages8
JournalJournal of Nuclear Medicine
Volume44
Issue number5
StatePublished - May 2003

Keywords

  • Folate receptor
  • In
  • Ovarian carcinoma
  • Tumor imaging

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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