TY - JOUR
T1 - Evaluation of 111In-DTPA-folate as a receptor-targeted diagnostic agent for ovarian cancer
T2 - Initial clinical results
AU - Siegel, Barry A.
AU - Dehdashti, Farrokh
AU - Mutch, David G.
AU - Podoloff, Donald A.
AU - Wendt, Richard
AU - Sutton, Gregory P.
AU - Burt, Robert W.
AU - Ellis, P. Ron
AU - Mathias, Carla J.
AU - Green, Mark A.
AU - Gershenson, David M.
PY - 2003/5
Y1 - 2003/5
N2 - 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.
AB - 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.
KW - Folate receptor
KW - In
KW - Ovarian carcinoma
KW - Tumor imaging
UR - http://www.scopus.com/inward/record.url?scp=0038621645&partnerID=8YFLogxK
M3 - Article
C2 - 12732670
AN - SCOPUS:0038621645
SN - 0161-5505
VL - 44
SP - 700
EP - 707
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 5
ER -