Reliability and reproducibility of etarfolatide as a folate receptor (FR)-targeted diagnostic imaging agent

Objectives FR is overexpressed in many cancers and can be a useful biomarker to select patients for targeted therapy. This study assessed the reliability and reproducibility of ^99mTc-etarfolatide, a FR-targeted SPECT imaging agent, to identify patients with FR-positive lesions.

Methods Target lesions of patients with platinum-resistant ovarian cancer were selected according to RECIST 1.0 criteria based on CT scans. SPECT images of the lesions were taken and ^99mTc-etarfolatide uptake was assessed by 2 independent nuclear medicine radiologists and 1 adjudicator. A total of 60 patients were classified as FR(10-100%) [≥1positive lesion] or FR(0%) [no positive lesions], and as FR(100%) [all lesions positive] or FR(0-90%) [no or < all lesions positive]. Lesions located in/near organs of high background were considered non-evaluable for SPECT images. All hepatic lesions were considered FR-positive. The radiologists were asked to re-read 20 cases after ≥28 days from their first read.

Results For the identification of FR(10-100%) vs FR(0%) patients, the readers’ agreement was 87% (95%CI: 75.4-94.1). Eight cases were read as FR(0%) and FR(10-100%) and required adjudication, with 2 patients classified as FR(0%), and 6 patients classified as FR(10-100%). For the identification of FR(100%) vs FR(0-90%) patients, the agreement rate was 85% (95% CI: 73.4-92.9). Nine cases were read as FR(0-90%) and FR(100%) and needed adjudication, with 2 patients classified as FR(0-90%) and 7 patients classified as FR(100%). The reproducibility of the reads as assessed by the same radiologist was high for the 2 readers in the identification of both FR(10-100%) vs FR(0%) patients (90% and 95%, respectively) and FR(100%) vs FR(0-90%) patients (100% and 95%, respectively).

Conclusions ^99mTc-etarfolatide imaging is a reliable and reproducible method to identify patients who may benefit from FR-targeted therapy.

Research Support This work was supported by Endocyte, Inc., West Lafayette, IN.