Use of technetium-99m-pyrophosphate single-photon emission computed tomography/computed tomography in monitoring therapeutic changes of RNA interference therapeutics in patients with hereditary transthyretin amyloid cardiomyopathy

Yi-Hsin Hung; An-Li Yu; Yi-Chieh Chen; Cheng-Hsuan Tsai; Mao-Yuan Su; Chia-Tung Shun; Hsueh-Wen Hsueh; Jimmy Jyh-Ming Juang; Ming-Jen Lee; Ping-Huei Tseng; Chia-Hua Hsu; Sung-Tsang Hsieh; Chi-Lun Ko; Kon-Ping Lin; Wen-Chung Yu; Mei-Fang Cheng; Chi-Chao Chao; Yen-Hung Lin

doi:10.1016/j.jfma.2024.10.005

Use of technetium-99m-pyrophosphate single-photon emission computed tomography/computed tomography in monitoring therapeutic changes of RNA interference therapeutics in patients with hereditary transthyretin amyloid cardiomyopathy

J Formos Med Assoc. 2024 Oct 10:S0929-6646(24)00481-9. doi: 10.1016/j.jfma.2024.10.005. Online ahead of print.

Authors

Yi-Hsin Hung¹, An-Li Yu², Yi-Chieh Chen³, Cheng-Hsuan Tsai⁴, Mao-Yuan Su⁵, Chia-Tung Shun⁶, Hsueh-Wen Hsueh⁷, Jimmy Jyh-Ming Juang¹, Ming-Jen Lee⁷, Ping-Huei Tseng⁸, Chia-Hua Hsu⁷, Sung-Tsang Hsieh⁷, Chi-Lun Ko³, Kon-Ping Lin⁹, Wen-Chung Yu¹⁰, Mei-Fang Cheng¹¹, Chi-Chao Chao¹², Yen-Hung Lin¹

Affiliations

¹ Department of Internal Medicine, Division of Cardiology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
² Department of Internal Medicine, Division of Cardiology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, Division of Cardiology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan.
³ Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
⁴ Department of Internal Medicine, Division of Cardiology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; National Taiwan University College of Medicine, Graduate Institute of Clinical Medicine, Taipei, Taiwan.
⁵ Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Imaging and Radiological Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan.
⁶ Department of Forensic Medicine and Pathology, National Taiwan University Hospital, Taipei, Taiwan.
⁷ Department of Neurology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
⁸ Department of Internal Medicine, Division of Gastroenterology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
⁹ Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan.
¹⁰ Department of Internal Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Cardiovascular Center, Taipei Veterans General Hospital, Taipei, Taiwan.
¹¹ Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Institute of Environmental and Occupational Health Sciences, National Taiwan University, Taipei, Taiwan. Electronic address: meifang@ntuh.gov.tw.
¹² Department of Neurology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address: ccchao@ntu.edu.tw.

PMID: 39389803
DOI: 10.1016/j.jfma.2024.10.005

Abstract

Background: RNA interference therapeutics reduce transthyretin production; however, their effect on hereditary transthyretin amyloid cardiomyopathy (ATTR-CA) remains unclear. We aimed to investigate alterations in technetium-99 m (^99mTc)-pyrophosphate (PYP) single-photon emission computed tomography/computed tomography (SPECT/CT) outcomes in patients receiving patisiran or vutrisiran.

Methods: We retrospectively identified individuals with hereditary ATTR-CA who received patisiran or vutrisiran. First and second ^99mTc-PYP SPECT/CT data, including visual grading, planar heart to contralateral lung (H/CL) ratio, and volumetric heart to lung (H/L) ratio were assessed.

Results: Eight patients with hereditary ATTR-CA were enrolled. Cohort A included four patients who underwent their first ^99mTc-PYP SPECT/CT imaging at the initiation of small interfering RNA (siRNA) treatment, while cohort B comprised four patients who had been receiving siRNA treatment before their first ^99mTc-PYP SPECT/CT imaging (median duration 1281 days). Overall, there were numerical reductions in planar H/CL ratio (1.7 ± 0.2 to 1.6 ± 0.1, p = 0.050) and a significant improvement in volumetric H/L ratio (4.0 ± 0.9 to 3.5 ± 0.4, p = 0.035). Although without significance, subgroup analysis showed more pronounced changes in cohort A for both planar H/CL ratio and volumetric H/L ratio (-20.1 ± 12.6% and -17.1 ± 11.4%) compared to cohort B (-3.3 ± 11.2% and -4.3 ± 12.7%).

Conclusion: Our results demonstrated a significant decrease in volumetric H/L ratio in hereditary ATTR-CA patients receiving RNA interference therapeutics.

Keywords: (99m)Tc‐pyrophosphate; Hereditary transthyretin amyloidosis; RNA interference therapeutics; Single‐photon emission computed tomography/computed tomography.