# S1PR1-targeted PET imaging to predict and monitor response to HER2-targeting antibody-drug conjugates > **NIH NIH R21** · WASHINGTON UNIVERSITY · 2024 · $399,829 ## Abstract PROJECT SUMMARY/ABSTRACT – In patients with gastric cancers who are clinically classified as HER2- positive, antibody-drug conjugates (ADC) prolong progression-free and overall survival. However, not all gastric tumors benefit from these therapies, or even those who initially respond inevitably develop resistance over time. Complementary biomarkers and methods are therefore needed to identify patients that will respond or develop resistance to HER2-targeting ADC therapies. Preclinical data we obtained in HER2 heterogeneous gastric patient-derived xenografts (PDXs) demonstrate that tumoral sphingosine-1-phosphate receptor (S1PR1) associate with tumors’ response to ADCs. Here, we will validate a S1PR1-targeted imaging approach (that is already used in the clinics for non-cancer applications) that allows quantitative measurements of S1PR1 to evaluate the early response to ADC treatment in mouse models of gastric cancer. We will correlate HER2 membrane availability, tumoral S1PR1, and the presence of genetic alterations with gastric tumor response to ADCs. We will perform randomized imaging and therapeutic studies in gastric PDXs to identify biological features that confer tumor sensitivity and resistance to ADCs. Aim 1 will use molecular imaging approaches involving positron emission tomography (PET) to further investigate the role of S1PR1 in ADC efficacy. Our innovative approach can quantitatively measure ADC-tumor binding through immunoPET and S1PR1 through a radiolabeled small molecule in the same subject and in real-time in gastric PDXs. Our studies will show that our imaging approaches, combined with analyses at the tissue level, can quantitatively detect different levels of early response to ADC therapy in gastric tumors, providing a strong impact. Aim 2 will further establish PET to determine the potential of modulating tumoral S1PR1 to reverse ADC resistance in gastric tumors. We will measure changes in HER2 and S1PR1 in response to treatments that enhance ADC efficacy. For each study, we will correlate the magnitudes of changes in our imaging biomarkers to a longer- term therapeutic outcome, as well as determine which combinations of multiple biomarkers improve the evaluation of early treatment response. This project could provide an excellent foundation for many future investigations, including the clinical translation of PET imaging approaches to predict and monitor tumor response to ADCs and the potential broader application to other membrane receptors and heterogeneous tumors. The long-term translational objectives of the studies proposed are to establish a foundation for a clinical study using imaging approaches of antibody-tumor accumulation and S1PR1 as predictive biomarkers of tumors response to HER2-targeting antibody drugs. ## Key facts - **NIH application ID:** 10937435 - **Project number:** 1R21CA291680-01 - **Recipient organization:** WASHINGTON UNIVERSITY - **Principal Investigator:** Patricia Manuela Ribeiro Pereira - **Activity code:** R21 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $399,829 - **Award type:** 1 - **Project period:** 2024-07-16 → 2026-06-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10937435 ## Citation > US National Institutes of Health, RePORTER application 10937435, S1PR1-targeted PET imaging to predict and monitor response to HER2-targeting antibody-drug conjugates (1R21CA291680-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10937435. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*