A Pilot Study to Correlate 4-[18F]fluoro-1-naphthol PET/CT Imaging with Chronic Graft Versus Host Disease Manifestations

About This Grant

ABSTRACT / PROJECT SUMMARY Allogeneic hematopoietic cell transplant (alloHCT) is a curative therapy for many life-threatening hematologic malignancies but its full therapeutic potential is undermined by complications such as chronic graft-versus-host disease (GVHD). Chronic GVHD is the greatest cause of non- relapse mortality and develops in 25-50% of long-term survivors of alloHCT. Novel approaches are needed to diagnose and treat chronic GVHD after alloHCT. 4-[18F]fluoro-1-naphthol ([18F]4FN) is a novel radiotracer that is specific to high energy reactive oxygen and nitrogen species produced during the respiratory burst in the active innate immune system. The proposed pilot study will apply [18F]4FN PET/CT to 16 patients with joint and other manifestations of chronic GVHD to obtain preliminary estimates of the anatomic and temporal correlations between [18F]4FN PET/CT signal intensity / location and chronic GVHD manifestations. Although PET, CT, and MRI have previously been used to image chronic GVHD, our approach differs by the use of [18F]4FN which reflects the functional activity of the innate immunity as indicated by respiratory burst intensity in contrast to glucose uptake as in [18F]fluoro-2-deoxyglucose (FDG) PET or anatomical changes as in CT and MRI. Patients will receive one to three [18F]4FN PET/CT scans and six to twelve Chronic GVHD Assessments. Data from these endpoints will be used to calculate preliminary estimates of the utility of [18F]4FN PET/CT as a predictive and prognostic / pharmacodynamic biomarker. We will test the following hypotheses with our specific aims: 1) [18F]4FN PET/CT images correlate anatomically with chronic GVHD manifestations and selected [18F]4FN PET/CT images will precede chronic GVHD manifestation changes. 2) [18F]4FN PET/CT images will provide pharmacodynamic metrics for treatment of chronic GVHD. Information gained from this pilot study will form the scientific basis for a subsequent larger phase II imaging trial to evaluate [18F]4FN PET/CT as a quantitative, predictive, and prognostic / pharmacodynamic biomarker for chronic GVHD. [18F]4FN PET/CT could be applied to other inflammatory conditions such as acute GVHD and cytokine release syndrome / immune effector cell associated neurotoxicity syndrome after CAR T cell infusion, and rheumatologic diseases. This multiple principal investigator project combines the unique, complementary expertise of Drs. Chen (alloHCT, chronic GVHD) and Piwnica-Worms (molecular imaging, radiopharmaceuticals). In 2022-2023, MD Anderson Cancer Center performed 416 adult alloHCTs of which 13.5% developed chronic GVHD within 1 year.