Professor Jonathan Wall, Ph.D., Distinguished Professor and Director of the University of Tennessee Graduate School of Medicine’s Amyloidosis and Cancer Theranostics Program speaks about the ASH 2021 Abstract – 2952 Detection of Systemic AL Amyloidosis By 124I-p5+14 PET/CT Imaging – Providing the Complete Picture for Diagnosis.
Link to Abstract:
https://ash.confex.com/ash/2021/webprogram/Paper154327.html
Background:
The deposition of fibrils in abdominothoracic organs, particularly the heart, liver, spleen, and kidneys, is associated with Immunoglobulin light chain-associated (AL) amyloidosis, resulting in organ failure and substantial morbidity. The fluctuating quantities of amyloid load and the varied organ presentation of amyloid make accurate and speedy diagnosis difficult. Organ biopsy and inferences based on anatomic imaging or changes in serum and urine biomarkers are currently the most prevalent methods for determining organ involvement. In the United States, there are currently no approved radiotracers for non-invasive detection of AL amyloid burden in key organs.
To overcome this, we created 124I-p5+14 (AT-01), a synthetic peptide radiotracer suited for PET/CT imaging. Through multivalent electrostatic interactions with amyloid-associated glycosaminoglycans and fibrils, this peptide binds to a variety of amyloid forms. Wall, J.S. et al. (2015) Molecules, 20, 7657) established the peptide’s particular reactivity with several types of amyloid in preclinical experiments. Peptide p5+14 was labeled with iodine-124 and tested in a Phase 1/2 PET/CT imaging trial of patients with systemic amyloidosis based on these findings (NCT 03678259).
We present the results of a study that included 23 patients with systemic AL amyloidosis and 5 healthy volunteers. Patient and organ-based sensitivity of 124I-p5+14 uptake in the heart, liver, spleen, and kidney are among the efficacy endpoints.
Methods:
Subjects who are over the age of 18 and have a confirmed diagnosis of AL amyloidosis based on organ or abdominal fat pad biopsy findings, as well as organ-related biomarker alterations. Heparin-treated patients were not allowed to participate. The subjects were given a 2 mg IV infusion of 124I-p5+14 (2 mCi) and images were taken 5-6 hours later with a Biograph PET/CT with a low dose CT. The organ-based distribution of amyloid was identified prior to imaging based on a study of the medical record. A reader blinded to patient-related clinical data assessed PET/CT pictures for visual uptake of radiotracer. The visual interpretation of the photographs by a reader blinded to organ involvement and the organ involvement based on the clinical record were compared to evaluate patient and organ-specific sensitivity.
Results:
The study included 23 patients with systemic amyloidosis and five healthy volunteers. There were no subjects who dropped out or were lost to follow-up. Radioactivity was seen in the parotid, salivary, and thyroid glands, as well as saliva, stomach lumen, and urine in the ureters and bladder, in healthy participants, confirming the biodistribution of free radioiodide. There was no uptake in the abdominothoracic organs. Patients with AL amyloidosis, on the other hand, showed uptake in the heart (71%), kidneys (61%), spleen (43%), liver (30%), pancreas (30%), lung, bone marrow, and other organs.
Patients exhibiting visual uptake in at least one anatomic site had a sensitivity of 96 percent (22/23). The organ-based sensitivity (13/14 heart; 3/3 liver; 1/1 spleen; 7/10 kidney) was 86 percent (13/14 heart; 3/3 liver; 1/1 spleen; 7/10 kidney). The patient who did not have cardiac uptake had been diagnosed for 8 years and had received successful stem cell transplant therapy for 7 years. PET/CT imaging found 68 percent more abdominothoracic organs (47 vs 28) than clinical examination (16/14 heart; 7/3 liver; 10/1 spleen; 14/10 kidney).
Conclusion:
PET/CT amyloidosis imaging with 124I-p5+14 allows for the accurate detection of AL amyloid deposits in many organ systems. Clinically undiagnosed amyloid was found in a variety of anatomic locales, with 124I-p5+14 detecting amyloid in 68 percent more abdominothoracic organs than was noted in the clinical record. Non-invasive PET/CT imaging with 124I-p5+14 can increase amyloid detection throughout the body, giving a more complete picture of the disease and possibly allowing for disease progression monitoring.