Estimating cancer risk from 99m Tc pyrophosphate imaging for transthyretin cardiac amyloidosis

Increasing recognition that transthyretin cardiac amyloidosis (ATTR-CA) is much more common than previously appreciated and the emergence of novel disease-modifying therapeutic agents have led to a paradigm shift in which ATTR-CA screening is considered in high-risk populations, such as patients with heart failure with preserved ejection fraction (HFpEF) or aortic stenosis. Radiation risk from 99mTc-pyrophosphate (99mTc-PYP) scintigraphy, a test with very high sensitivity and specificity for ATTR-CA, has not been previously determined. Radiation doses to individual organs from 99mTc-PYP were estimated using models developed by the Medical Internal Radiation Dose Committee and the International Commission on Radiological Protection. Excess future cancer risks were estimated from organ doses, using risk projection models developed by the National Academies and extended by the National Cancer Institute. Excess future risks were estimated for men and women aged 40-80 and compared to total (excess plus baseline) future risks. All-organ excess cancer risks (90% uncertainty intervals) ranged from 5.88 (2.45,11.4) to 12.2 (4.11,26.0) cases per 100,000 patients undergoing 99mTc-PYP testing, were similar for men and women, and decreased with increasing age at testing. Cancer risks were highest to the urinary bladder, and bladder risk varied nearly twofold depending on which model was used. Excess 99mTc-PYP-related cancers constituted < 1% of total future cancers to the critical organs. Very low cancer risks associated with 99mTc-PYP testing suggest a favorable benefit-risk profile for 99mTc-PYP as a screening test for ATTR-CA in high-risk populations, such as such as patients with HFpEF or aortic stenosis.