Abstract
2822
Introduction: The amyloid imaging agent, iodine (124I) evuzamitide (aka 124I-p5+14; 124I-AT-01), is being developed for the detection of systemic amyloid deposits, of any type, by PET/CT imaging. There are no approved radiotracers that bind directly to amyloid components and that can yield quantitative detection of all types of amyloid in all abdominothoracic organs. This reagent could provide a facile, first-line method for the diagnosis of amyloidosis as well as permit quantitative longitudinal imaging for monitoring organ-specific progression or regression of disease. In the first-in-human imaging study at the University of Tennessee Medical Center (NCT03678259), one patient with multi-organ AL amyloidosis received two exposures of the radiotracer 23 mos apart. Here we report a case study of this subject where quantitation of amyloid in the heart, liver, spleen and kidneys was assessed from PET/CT images by using both manual (single slice) and automated (fully 3D) methods. These data are evaluated in the context of clinical biomarkers of organ function. The data suggest a correlation between hepatic function and amyloid regression in the liver; however, despite reductions in hepatosplenic amyloid, based on imaging, similar decreases in cardiac and renal amyloid were not observed.
Methods: Patient P07, a 72-year-old man, presented with abnormal liver function tests, notably increased alkaline phosphatase. Biopsy of the liver and celiac nodes both showed presence of AL amyloid. The patient received ~2 mCi 124I-p5+14 and PET/CT imaging in May 2019 and April 2021 and was on daratumumab-based therapy. PET/CT images were acquired at 5 h post injection using a Biograph 16 TruePoint with a low dose CT (120 kVp, 50 effective mAs). The entire liver, spleen, kidneys, heart, and aorta were automatically segmented on the CT image using a pretrained 3D U-net convolutional neural network (TRAQinform IQ technology, AIQ Solutions). The contours were used to quantify the mean standardized uptake value (SUV) in each organ normalized by the mean aorta lumen radioactivity (3D SUVRmean). Separately, the fully manual 2D ROI analysis was performed on a single representative slice of each organ, resulting in 2D SUVRmean outputs. Serum free light chain and biomarkers of hepatic and renal function (AST, ALT, Alk. phos., Cre., BUN) were collected as standard of care, whereas NT-proBNP was collected coincident with imaging.
Results: The PET images indicated amyloid uptake of the radiotracer in the heart, spleen, liver, kidneys, pancreas and bone marrow, with physiological distribution of radioactivity in the parotid and salivary glands, stomach lumen and urinary bladder. At the later time point, hepatosplenic radioactivity had visually decreased relative to heart and kidney. Quantitative analysis of PET/CT images by manual 2D and automated 3D methods correlated significantly (rP < 0.98; p < 0.02). Changes in hepatic, splenic, renal and cardiac uptake were -22.6%, -53.2%. +13.1%, +18.2% for the manual method, and -25.5%, -56.3%, +12.9%, +19.64% for the automated method. Concurrently, serum free light chain levels and serum alkaline phosphatase decreased from ~200 IU/mL to ~120 IU/mL.
Conclusions: Organ-specific regression of amyloid deposits can be visualized using iodine (124I) evuzamitide, occurring with concomitant recovery in organ function serum biomarkers. However, reduction in hepatosplenic amyloid may occur in the context of increasing amyloid deposition in the heart and kidneys. Organ-specific amyloid regression and progression, and biomarker-based response to therapy following anti-plasma cell therapies, remains a complex phenomenon in patients with systemic AL amyloidosis.