Abstract 4232: PET imaging of galectin-3 expression with [18F]FPDTG for detection of early breast carcinoma lesions in dense breast tissue

Mammography is the gold standard for breast cancer detection with sensitivity of 85%, which decreases to 68% in women with dense breasts and to 48% in women with extremely dense breasts, making cancer detection challenging. Additional methods for breast cancer screening have been developed, including: contrast-enhanced mammography, tomosynthesis, automated whole breast ultrasound, advanced MRI and molecular imaging (99mTc-MIBI gamma camera; 18F-FDG). However, early detection and differential diagnosis of malignant vs benign breast lesions remains a major challenge in patients with dense breasts. We have been developing novel approaches to early detection and differential diagnosis of malignant vs benign breast lesions using PET imaging of galectin-3 (Gal-3), that is significantly overexpressed in breast carcinomas, as compared to pre-malignant lesions. We developed a novel radiotracer 3-[18F]fluorophenylthio-digalactoside (18F-FPTDG) with high binding affinity (Kd 14 nM) and specificity to Gal-3. In vitro radiotracer binding studies in a panel of MCF10-derived cell lines with different degrees of malignancy and Gal-3 expression, demonstrated a highly significant linear relationship between the level of Gal-3 expression and the magnitude of 18F-FPTDG binding to cell membranes (R2 = 0.99). Preliminary in vivo PET imaging studies with 18F-FPTDG in mice bearing MCF10DCIS tumor xenografts demonstrated a rapid bi-exponential clearance of 18F-FPTDG from the blood (fast and slow clearance half-times: 0.5 and 10.5 min, respectively). 18F-FPTDG cleared predominantly via the hepatobiliary route, as evidenced by high levels of radioactivity in the liver, increasing levels in duodenum and upper intestinal tract. The liver and kidney clearance followed mono-exponential kinetics with half-times of ∼120 min and 37 min, respectively. Renal clearance was more active in mice, as evidenced by higher amounts of radioactivity in the bladder. The magnitude of catabolism of [18F]FPDTG was negligible, as evidenced by very low levels of [18F]F2 accumulation in the bone at 60-75 min post injection. The level of accumulation of [18F]FPDTG-derived radioactivity in the lungs, muscles, and other organs and tissues was extremely low. Also, there was no measurable levels of [18F]FPDTG-derived radioactivity in the brain. In contrast, there were distinct regions in the breast carcinoma xenograft with higher levels of [18F]FPDTG, especially in the central regions (hypoxia). The half-time clearance of [18F]FPDTG from tumors was ∼8 min, which was about twice longer than clearance half-time from lungs and muscles - 4.5 and 4 min, respectively. Additional studies are being conducted in various breast tumor xenograft models, as well as in PyVmT transgenic mice, to assess the utility of PET/CT with [18F]FPDTG for differential diagnosis of benign vs malignant breast lesions and for biopsy guidance. Citation Format: Robin E. Bonomi, Vadim Popov, Thomas Mangner, Avraham Raz, Anthony F. Shields, Juri G. Gelovani. PET imaging of galectin-3 expression with [18F]FPDTG for detection of early breast carcinoma lesions in dense breast tissue. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4232.