Exploratory study of 99mTc-EC20 imaging for identifying patients with folate receptor-positive solid tumors

Tc-99m-EC20 is a folate receptor (FR)-targeted imaging agent consisting of the vitamin folate conjugated to Tc-99m. FR is expressed on a variety of epithelial cancers, with advanced cancers often expressing FR at significantly higher levels than earlier stages of the disease. The goals of this pilot study were to determine the percentages of various solid tumors that accumulate Tc-99m-EC20 in vivo and to correlate Tc-99m-EC20 uptake with immunohistochemistry (IHC) analysis of FR expression in available biopsied tumor tissue. Methods: A total of 154 patients with proven or suspected cancer and at least one lesion of >= 1.5 cm underwent imaging with Tc-99m-EC20. The majority of these patients (77%) had a diagnosis of renal cell carcinoma. The remaining patients had a variety of other solid tumors. Whole-body planar images were obtained 1-2 h after injection, followed by SPECT of the region containing index lesions. The uptake of Tc-99m-EC20 in tumors was scored as no uptake, mild uptake, or marked uptake. The resultant Tc-99m-EC20 data were analyzed for correlation with the expression of the a-isoform of FR, as determined by IHC analysis, in tissue available from prior or subsequent surgery or biopsy. Results: The administration of Tc-99m-EC20 was well tolerated. Tumors with increased (99m)TcEC20 uptake were identified in 68% of patients, and IHC results were positive for the expression of the a-isoform of FR in 67% of patients. The agreement between methods was 61% overall (kappa = 0.096; 95% confidence interval = -0.085 to 0.277), with 72% agreement of positive results and 38% agreement of negative results. Conclusion: In vivo imaging with Tc-99m-EC20 identified approximately two thirds of patients as having FR-positive tumors. Agreement between imaging and in vitro IHC was poor but was potentially confounded by a lack of correlation between the time of tissue sampling and the time of Tc-99m-EC20 imaging, the heterogeneous expression of FR in metastatic lesions from the same patient, and the inability to detect the P-isoform of FR by IHC. This pilot study of Tc-99m-EC20 scintigraphy indicates that the agent is safe and well tolerated and that this non-invasive procedure may have utility in selecting patients likely to benefit from FR-targeted therapy.