Quantification of Peptide ¹²⁴I-p5+14 (AT-01) Uptake in Patients with Systemic Amyloidosis.

Objectives: The amyloid imaging agent, peptide p5+14 (AT-01), has been developed for the detection of systemic amyloid deposits by PET/CT imaging. At present, 42 patients with amyloidosis of varied types have completed a first-in-human imaging study at the University of Tennessee Medical Center (NCT03678259). Evaluating the uptake of the radiotracer in major abdominothoracic organs is a key goal of the trial. Accurate quantification of radioactivity, and by extension amyloid load in the major organs, will permit longitudinal monitoring of the pathology and assessment of progression or regression of amyloid burden in response to therapy.

Methods: The first 26 patients, administered 11 MBq (n=1), 37 MBq (n=4), or 74 MBq (n=21) of iodine-124 and ~1.4 mg peptide were evaluated. PET/CT images were acquired using a Biograph 16 TruePoint with a low dose CT (120 kVp, 50 effective mAs). Whole body images were acquired 5 h post injection. PET data were reconstructed using a 3DOSEM algorithm with attenuation weighting and prompt gamma correction yielding an image matrix of 168 x 168 and an image resolution of ~8 mm full width half maximum. Images were initially analyzed by a single reviewer (Rev1) within 3 wk of acquisition (from November 2018 - June 2020). To assess the accuracy of these measurements the images were reevaluated by Rev1 and by a second reviewer (Rev2) in October 2020 and the data compared using correlation analyses. Images were analyzed using Inveon Research Workplace (IRW) software (Ed. 4.2 [4.2.0.15]) and Graphpad Prism ver. 8.3.0.

Results: Pearson correlation analyses between original Rev1 data and new Rev1 and Rev2 analyses for the heart, kidney, liver, spleen, left ventricular wall and lumen of the thoracic aorta yielded r > 0.95 for all (two-tailed p <0.0001). Linear regression analysis resulted in R² > 0.9 and a slope of ≥ 0.9, indicating a significantly high inter-rater (Rev1 and Rev2) and intra-rater reliability (Rev1). Conclusion: A facile region of interest analysis can be used to quantify the uptake of ¹²⁴I-p5+14 in abdominothoracic organs and provide the basis for a routine method for quantifying amyloid load in patients with systemic amyloidosis. Acknowledgements: Support for this work comes from the Amyloidosis and Cancer Theranostics Program gift fund. We appreciate the support of the Cancer Institute and Department of Nuclear Medicine at the University of Tennessee Medical Center. Attralus Inc. owns intellectual property associated with ¹²⁴I-p5+14 (AT-01).

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