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.


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). (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.


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 (111)In-DTPA-folate scintigraphy was 76% and 82% for the masked and unmasked analyses, respectively.


CONCLUSIONS
(111)In-DTPA-folate is safe, and possibly effective, for scintigraphy differentiating between malignant and benign ovarian masses.
Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. siegelB@mir.wustl.edu
Barry A
BA
Siegel
Farrokh
F
Dehdashti
David G
DG
Mutch
Donald A
DA
Podoloff
Richard
R
Wendt
Gregory P
GP
Sutton
Robert W
RW
Burt
P Ron
PR
Ellis
Carla J
CJ
Mathias
Mark A
MA
Green
David M
DM
Gershenson
D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000032:analysis*; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000378:metabolism*; D006801:Humans; D007205:Indium Radioisotopes; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging*; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000378:metabolism*; D011877:Radionuclide Imaging; D011956:Receptors, Cell Surface; D012680:Sensitivity and Specificity
D002352:Carrier Proteins; C108951:DTPA folate; D058973:Folate Receptors, GPI-Anchored; D007205:Indium Radioisotopes; D011956:Receptors, Cell Surface; D004369:Pentetic Acid; D005492:Folic Acid