TY - JOUR T1 - Time resolved biodistribution of peptide 124I-p5+14 in patients with systemic AL amyloidosis JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 3127 LP - 3127 VL - 61 IS - supplement 1 AU - Alan Stuckey AU - EMILY MARTIN AU - Dustin Powell AU - Yitong Fu AU - Myrwood Besozzi AU - Sarah Hall AU - Steve Kennel AU - Jonathan Wall Y1 - 2020/05/01 UR - http://jnm.snmjournals.org/content/61/supplement_1/3127.abstract N2 - 3127Introduction: We have developed a synthetic peptide designated 124I-p5+14, for PET/CT imaging of patients with systemic amyloidosis. Based on positive preclinical data demonstrating reactivity with many forms of amyloid, p5+14 was labeled with iodine-124 for a Phase I PET/CT imaging trial (clinicaltrials.gov NCT 03678259) Three patients were enrolled in part 1 of the study to assess radiation dosimetry and evaluate the kinetic behavior of the peptide in blood and organs. The patients were given doses in a two-step dose escalation of radioactivity - one patient received 0.3 mCi and two were administered approximately 1 mCi. PET/CT images were acquired serially over 48 hours post-injection. Objectives: The aim for Part 1 of the clinical trial was to generate biodistribution data for up to 48 hours post injection of 124I-p5+14. These data would be used to estimate organ-related dosimetry and establish the injected dose for the rest of the patients to be enrolled in the study. Methods: Three patients >18 y of age with AL amyloidosis and, clinical involvement of two or more organ systems and not requiring heparin therapy were eligible. Subjects received <2mg of 124I-p5+14 and either 0.3 mCi or 1 mCi of 124I administered as a single IV infusion. Whole body PET/CT images and blood samples were acquired at 25 min, 50 min, 2 h, 3 h, 6 h, 24 h, and 48 h post injection. Radiotracer uptake in organs was quantified using region of interest analysis and expressed as organ-to-blood ratios. Organ dosimetry estimates were calculated using OLINDA-EXM. Results: All three patients demonstrated visible uptake in organs including the heart, lung, spleen, and kidneys. The gender-averaged mean whole body effective dose was determined to be 0.24 ± 0.02 mSv/MBq with a coefficient of variation of 9.5. The highest organ dose was received by the salivary glands and thyroid. Blood clearance data were analyzed using a two phase exponential decay model which yielded a fit to the data (R2 > 0.99 for all data) with fast and slow half-life estimates of ~ 15 min and ~700 min. Organ specific clearance varied depending on the presence of amyloid. Notably, an increase in radioactivity occurred, up to 6 h pi, in the positive heart tissue. Conclusions: Radioioidnated peptide 124I-p5+14 was visible in organs considered clinically to contain amyloid. The peptide was eliminated via renal excretion, which (due to dehalogenation) resulted in free radioiodide that was subsequently eliminated via the gastrointestinal tract. Therefore, at later time points post-injection radioactivity associated with the kidney can be interpreted as being indicative of amyloid. The radiation dosimetry findings suggest that a 2 mCi imaging dose would result in acceptable exposure to the patients undergoing this imaging study. Acknowledgements: This study was supported in part by the National Heart Lung and Blood Institute, National Institutes of Health, through the Science Moving TowArds Research Translation and Therapy (SMARTT) program via the following contract(s) HHSN268201600011C, HHSN268201600012C, and HHSN268201600014C, as well as by contributions from CMC Steel TN to the ACTP Gift Fund at the UTGSM and support from UHS. In addition, we thank Michael Stabin, PhD, Brett Hines, Carmella Moody, PhD and Derry Ridgway, MD and the many patients for their support. ER -