Preliminary Observations Using 99m-Tc-Peptide p5+14 for the Detection of AL Amyloidosis Using SPECT/CT and Planar Gamma Scintigraphic Imaging

Background: Immunoglobulin light chain (AL) amyloidosis is a systemic protein folding disorder associated with a monoclonal plasma cell dyscrasia. Fibrillar aggregates of monoclonal free light chains, or fragments thereof, can deposit in any organ or tissue. Invariably, more than one anatomic site is involved, including the heart, liver, spleen, kidneys, pancreas, nerves, gastrointestinal tract and vasculature. Cardiac amyloidosis, which occurs in ~70% of patients, is clinically most ominous; however, amyloid in other sites can impact quality of life. We have developed a novel technetium-99m labeled pan-amyloid reactive peptide, p5+14, which is easily produced and could be used in the community setting as a rapid screening tool for AL amyloidosis, notably in patients with MGUS or multiple myeloma, who are at risk for developing AL. Here, we present preliminary observations from the Phase 1 study (NCT05951816) of ^99mTc-p5+14 in healthy subjects and patients with AL amyloidosis using planar gamma scintigraphy and SPECT/CT imaging.

Patient and Study Design: This is an investigator-initiated Phase 1, single-center, open-label, pilot study performed by the University of Tennessee Health Science Center College of Medicine-Knoxville. The four-part study will recruit a total of N=35 subjects: Five (n=5) healthy subjects, ten (n=10) patients with AL, and twenty (n=20) patients with ATTR amyloidosis. Subjects were administered ≤22 mCi of radiotracer intravenously. At 1 h and 3 h post-injection, subjects were imaged using whole body planar gamma scintigraphy and SPECT/CT imaging over the thorax. Blood was collected to assess serum biomarkers, and a transthoracic echocardiogram performed.

Results: Both the planar and SPECT/CT images of ^99mTc-p5+14 were of high quality at both 1 h and 3 h post-injection. No cardiac uptake of the radiotracer was seen in healthy subjects (n=5). Physiologic distribution of radioactivity was observed in the kidneys, ureter, renal bladder, and the liver, consistent with renal and hepatobiliary clearance of the radiotracer. In contrast, patients with cardiac AL amyloidosis had significant uptake of ^99mTc-p5+14 in the heart, specifically in the ventricular walls and interventricular septum. In addition, retention of the ^99mTc-p5+14 was seen in the salivary glands, spleen, and liver (discernable from the physiological uptake).

Conclusion: AL amyloidosis is a progressive, often fatal, plasma cell dyscrasia that is only diagnosed within the first year after symptom onset in ~56% of patients. Moreover, patients with MGUS, particularly a light chain MGUS, or multiple myeloma, are at risk for developing amyloidosis. At present, there are no approved imaging agents for detecting AL amyloidosis. Therefore, p5+14 peptide-based tracers like ^99mTc-p5+14 (and the iodine-124 labeled variant for PET/CT imaging) address a significant clinical unmet need. ^99mTc-p5+14 is easy to synthesize and can be used to detect cardiac AL amyloidosis using SPECT/CT imaging, the most widely used clinical imaging technique. This novel agent may be a useful contribution to the early, biopsy-free, diagnosis of AL amyloidosis in the community setting.

Acknowledgments: This study is supported by a grant from Attralus Inc, CA, USA. Peptide p5+14 was provided by Attralus Inc.

Wall:Attralus, Inc.: Current equity holder in private company, Current holder of stock options in a privately-held company, Patents & Royalties, Research Funding. Kennel:Attralus, Inc.: Current equity holder in private company, Patents & Royalties. Stuckey:Attralus, Inc.: Current equity holder in private company. Martin:Attralus, Inc.: Current equity holder in private company, Patents & Royalties.