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.
Siegel
Barry A
BA
Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. siegelB@mir.wustl.edu
Dehdashti
Farrokh
F
Mutch
David G
DG
Podoloff
Donald A
DA
Wendt
Richard
R
Sutton
Gregory P
GP
Burt
Robert W
RW
Ellis
P Ron
PR
Mathias
Carla J
CJ
Green
Mark A
MA
Gershenson
David M
DM
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