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Estimating cancer risk from 99mTc pyrophosphate imaging for transthyretin cardiac amyloidosis

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Journal of Nuclear Cardiology Aims and scope

Background

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.

Methods and Results

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.

Conclusion

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.

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Abbreviations

ATTR-CA:

Transthyretin cardiac amyloidosis

HFpEF:

Heart failure with preserved ejection fraction

99mTc-PYP:

99mTc-pyrophosphate

AL:

Light chain

TTR:

Transthyretin

BEIR:

Biological Effects of Ionizing Radiation

RadRAT:

Radiation Risk Assessment Tool

MIRD:

Medical Internal Radiation Dose

ICRP:

International Commission on Radiological Protection

SEER:

Surveillance Epidemiology and End Results

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Disclosures

AJE has received consulting fees from GE Healthcare, and his institution has received funding for research from GE Healthcare and Toshiba America Medical Systems. MSM and his institution receive funding for research and serving on advisory boards and DSMBs from Pfizer Inc., Alnylam Pharmaceuticals Inc., Ionis Pharmaceuticals, Prothena Inc. and Eidos, Inc.

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Authors and Affiliations

  1. Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center and New York-Presbyterian Hospital, 622 West 168th Street PH 10-203, New York, 10032, USA

    Andrew J. Einstein MD, PhD, FASNC, Adam Castaño MD, MS, Mathew S. Maurer MD & Sabahat Bokhari MD, FASNC

  2. Department of Radiology, Columbia University Irving Medical Center and New York-Presbyterian Hospital, New York, USA

    Andrew J. Einstein MD, PhD, FASNC & Akiva Mintz MD, PhD

  3. Center for Radiological Research, Columbia University Irving Medical Center, New York, USA

    Igor Shuryak MD, PhD

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  1. Andrew J. Einstein MD, PhD, FASNC
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  2. Igor Shuryak MD, PhD
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  3. Adam Castaño MD, MS
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  5. Mathew S. Maurer MD
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  6. Sabahat Bokhari MD, FASNC
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Correspondence to Andrew J. Einstein MD, PhD, FASNC.

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Funding

Supported by National Institutes of Health R01 HL109711 (AJE) and K24 AG036778 (MSM).

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Einstein, A.J., Shuryak, I., Castaño, A. et al. Estimating cancer risk from 99mTc pyrophosphate imaging for transthyretin cardiac amyloidosis. J. Nucl. Cardiol. 27, 215–224 (2020). https://doi.org/10.1007/s12350-018-1307-7

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  • DOI: https://doi.org/10.1007/s12350-018-1307-7

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