Abstract PS1-06-11: Fibroblast activation protein (FAP)-targeted dedicated breast PET for primary invasive lobular carcinoma: A pictorial review

Abstract Background Dedicated breast positron emission tomography (dbPET) is an innovative imaging technology specially designed to scan only the breasts, providing high spatial resolution and detailed characterization of tumor uptake levels, distribution, and textures. Fibroblast activation protein (FAP), predominantly expressed in cancer-associated fibroblasts within the tumor stroma, has recently gained significant attention as a promising target for cancer diagnostics and therapy. Recent whole-body PET/CT studies reported that novel FAP-targeted radiotracers showed higher sensitivity in the detection of primary and metastatic invasive breast cancer compared to the standard 18F-fluorodeoxyglucose (FDG) radiotracer. FAP-targeted radiotracers may offer unique advantages in depicting primary breast cancers, especially in invasive lobular carcinoma (ILC), which has unique imaging challenges due to its diffuse growth pattern and low cellularity. We present initial studies of FAP-targeted dbPET performed on the same day following whole-body PET/CT in patients with primary ILC lesions. Methods Patients with primary ILC were recruited from the participants of the Endocrine Optimization Program (EOP), a sub study of the I-SPY 2 TRIAL. After undergoing whole-body PET/CT with FAP-targeted radiotracer (6mCi +/-20% of 68Ga-FAP-2286) on a separate research protocol, they underwent dedicated breast imaging using the MAMMI dbPET scanner (OncoVision, Spain) without additional radiotracer injection. Due to the transportation of patients between two different PET scanner locations, the average interval between radiotracer injection and the start of dbPET scanning was approximately 2.5 hours. The dbPET scans were performed in the prone position, starting with the ipsilateral breast followed by the contralateral breast, with each scan taking approximately 15 minutes per breast. FAP-dbPET images were interpreted alongside DCE-MRI scans obtained closest to the FAP-dbPET scans. Results Four patients with primary ILC have underwent FAP-dbPET scanning to date: #1. 59 year old postmenopausal woman with Lt. ILC before treatment initiation #2. 78 year old postmenopausal woman with Rt. ILC before treatment initiation #3. 39 year old premenopausal woman with Lt. ILC after 4 weeks of neoadjuvant endocrine treatment #4. 51 year old premenopausal woman with bilateral ILC after 7 weeks of neoadjuvant endocrine treatment In all cases, known ILC lesions were clearly depicted on the dbPET as well as on the whole-bodyPET. Notably, for two patients, FAP-dbPET identified additional suspicious lesions with high uptake (pathology not confirmed) that were either uncertain or masked by background parenchymal enhancement in the DCE-MRI images. For individual patients, FAP-targeted dbPET will be presented along with whole-body PET/CT and DCE-MRI. Discussion Our preliminary study shows the promising capability of FAP-dbPET in visualizing tracer uptake of primary ILC with high resolution. These scans may provide better visibility of ILC lesions and provide a more accurate way to assess response to neoadjuvant treatment. In combination with novel tracers such as FAP that may provide unique insight into the biology of primary breast tumors and drug mechanism of action, dbPET provides a cost-effective and clinically-feasibly technology that will facilitate use of PET biomarkers in clinical trials testing novel drugs in the neoadjuvant setting. Based on these preliminary results, we plan to expand our FAP-dbPET study with advanced qualitative and quantitative analyses, over time, to better measure response to therapy and ultimately to help evaluate how best to target therapy in the setting of lobular cancer. Citation Format: N. Onishi, R. Mukhtar, T. Hope, P. Metanat, Y. Wang, B. Joe, K. Ray, S. Choi, L. Awni, D. Heditsian, D. Romer, S. Brain, I-SPY 2 Imaging Working Group, I-SPY 2 Investigator Network, J. Chien, L. Esserman, N. Hylton. Fibroblast activation protein (FAP)-targeted dedicated breast PET for primary invasive lobular carcinoma: A pictorial review abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-06-11.