In recent years, patients with Her2-positive breast cancer have benefitted greatly from targeted therapies such as Trastuzumab and Pertuzumab. However, there are currently no FDA-approved Her2-targeted imaging agents to diagnose and monitor Her2-positive breast cancer leaving physicians to rely on biopsies to determine Her2 status. Whole-body visualization of Her2 would allow the noninvasive identification of all Her2 primary and metastatic lesions as well as serve as a powerful tool to monitor the effectiveness of Her2-targeted therapeutics. We recently described the generation of Her2-targeted SUPR (Scanning Unnatural Protease Resistant) peptides that selectively bind the Her2 receptor in vitro with low nanomolar affinity. Cy5-labeled SUPR peptides showed rapid and Her2-specific tumor uptake and minimal retention in non-tumor tissues after 24 hours of washout. In this study, we describe 18F radiolabeling of Her2-targeted SUPR peptides and their evaluation as PET radiotracers to visualize Her2 expression in vivo. The lead compound, SUPR4, was labeled with 18F-fluoroethylazide in high radiochemical yield and specific activity on an automated radiochemical synthesis platform. The resulting radiotracer (SUPR-18F) showed rapid and Her2-selective tumor uptake between 30-60 minutes post-injection with minimal liver uptake. The majority of the tracer was cleared by the kidneys at 2 hours post-injection although some activity was observed in the GI tract suggesting hepatobiliary excretion. No significant uptake was observed in the brain. 90 minute dynamic PET scans were performed to estimate the rate of tumor uptake and clearance in major organ systems and the biodistribution quantified by autoradiography post-mortem. Pre-injection of unlabeled SUPR peptide, Trastuzumab, and Pertuzumab followed by PET imaging with SUPR-18F was used to confirm tumor uptake as a function of specific binding to the Her2 receptor. Having established the utility of SUPR-18F in pre-clinical mouse models, we anticipate that this class of PET tracers could be employed in same-day imaging procedures throughout the administration of Her2-targeted therapy.

Citation Format: Lindsay E. Kelderhouse, Amanda Hardy, Federica Pisaneschi, Joshua P. Gray, Seth Gammon, Richard W. Roberts, Terry T. Takahashi, Steve Fiacco, Steven W. Millward. SUPR-PET: Nuclear imaging of Her2-positieve breast cancer with SUPR peptides. [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 4236.