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Peer-reviewedCC BY 4.0European Journal of Nuclear Medicine and Molecular Imaging

The role of extracardiac radiotracer biodistribution in the evaluation of cardiac amyloidosis: a retrospective multicenter study on [99mTc]Tc-DPD and [99mTc]Tc-HMDP

7 affiliations
  1. 1Nuclear medicine, Alma Mater Studiorum University of Bologna, Bologna, 40138 Italy
  2. 2Department of Nuclear Medicine, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
  3. 3Nuclear Medicine Unit, Hospital Care Department of Radiology, Azienda Sanitaria Universitaria Giuliano Isontina, Trieste, Italy
  4. 4Nuclear Medicine Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy
  5. 5Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
  6. 6Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
  7. 7Tuscan Regional Amyloidosis Centre, Careggi University Hospital, Florence, Italy

Abstract

Background: Bone scintigraphy using [99mTc]Tc-DPD or [99mTc]Tc-HMDP is a non-invasive cornerstone for diagnosing transthyretin cardiac amyloidosis (ATTR-CA). However, their interchangeability and the clinical relevance of systemic extracardiac uptake (ExtCU) remain poorly defined.

Aim: To systematically compare the diagnostic performance and whole-body biodistribution profiles of [99mTc]Tc-DPD and [99mTc]Tc-HMDP in patients with suspected cardiac amyloidosis (CA).

Methods: We retrospectively evaluated a multicenter cohort of patients investigated for suspected CA who underwent late planar whole-body scintigraphy and targeted SPECT/CT with either radiotracer as part of their diagnostic workup. Inclusion required a final, confirmed diagnosis of ATTRwt, ATTRv, or AL amyloidosis. Myocardial visual Perugini score (VISUAL_PS) and systemic ExtCU (pulmonary, appendicular muscular, visceral, and miscellaneous) were recorded.

Results: The study included 224 patients (DPD: n = 109, comprising 70 ATTRwt, 20 ATTRv, 19 AL; HMDP: n = 115, comprising 90 ATTRwt, 13 ATTRv, 12 AL). In ATTRwt, the DPD cohort presented predominantly with Perugini Grade 2 (76%), whereas the HMDP cohort skewed toward Grade 3 (72%, p < 0.001). DPD was significantly associated with appendicular muscular uptake (ATTRwt: 84% vs. 38%, p < 0.001), creating a competitive “soft-tissue sink effect”. Conversely, HMDP demonstrated a unique predilection for pulmonary retention (ATTRwt: 68% vs. 46%, p = 0.008; ATTRv: 61% vs. 10%, p = 0.006). Visceral uptake was rare in ATTR but was a robust negative predictor strongly favoring AL amyloidosis (OR 0.016, p < 0.001).

Conclusions: [99mTc]Tc-DPD and [99mTc]Tc-HMDP possess distinct biodistribution profiles precluding direct interchangeability. HMDP maximizes myocardial contrast, whereas DPD provides a superior representation of the systemic musculoskeletal amyloid burden. Nuclear medicine physicians must adopt tracer-specific interpretive approaches to optimize non-invasive phenotyping.

Trial registration: not applicable.

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BibTeX
@article{giorgio2026role,
  title = {{The role of extracardiac radiotracer biodistribution in the evaluation of cardiac amyloidosis: a retrospective multicenter study on [99mTc]Tc-DPD and [99mTc]Tc-HMDP}},
  author = {Andrea Di Giorgio and Giacomo Battisti and Norma Bonazzi and Sonia Elisa Prisco and Maria Starace and Simone Longhi and Stefano Fanti and Valentina Berti and Francesco Cappelli and Rachele Bonfiglioli},
  journal = {European Journal of Nuclear Medicine and Molecular Imaging},
  year = {2026},
  month = oct,
  doi = {10.1007/s00259-026-08153-1},
  url = {https://doi.org/10.1007/s00259-026-08153-1},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - The role of extracardiac radiotracer biodistribution in the evaluation of cardiac amyloidosis: a retrospective multicenter study on [99mTc]Tc-DPD and [99mTc]Tc-HMDP
AU  - Andrea Di Giorgio
AU  - Giacomo Battisti
AU  - Norma Bonazzi
AU  - Sonia Elisa Prisco
AU  - Maria Starace
AU  - Simone Longhi
AU  - Stefano Fanti
AU  - Valentina Berti
AU  - Francesco Cappelli
AU  - Rachele Bonfiglioli
PY  - 2026
DA  - 2026/10/23
JO  - European Journal of Nuclear Medicine and Molecular Imaging
DO  - 10.1007/s00259-026-08153-1
UR  - https://doi.org/10.1007/s00259-026-08153-1
AB  - Background: Bone scintigraphy using [99mTc]Tc-DPD or [99mTc]Tc-HMDP is a non-invasive cornerstone for diagnosing transthyretin cardiac amyloidosis (ATTR-CA). However, their interchangeability and the clinical relevance of systemic extracardiac uptake (ExtCU) remain poorly defined.  Aim: To systematically compare the diagnostic performance and whole-body biodistribution profiles of [99mTc]Tc-DPD and [99mTc]Tc-HMDP in patients with suspected cardiac amyloidosis (CA).  Methods: We retrospectively evaluated a multicenter cohort of patients investigated for suspected CA who underwent late planar whole-body scintigraphy and targeted SPECT/CT with either radiotracer as part of their diagnostic workup. Inclusion required a final, confirmed diagnosis of ATTRwt, ATTRv, or AL amyloidosis. Myocardial visual Perugini score (VISUAL_PS) and systemic ExtCU (pulmonary, appendicular muscular, visceral, and miscellaneous) were recorded.  Results: The study included 224 patients (DPD: n = 109, comprising 70 ATTRwt, 20 ATTRv, 19 AL; HMDP: n = 115, comprising 90 ATTRwt, 13 ATTRv, 12 AL). In ATTRwt, the DPD cohort presented predominantly with Perugini Grade 2 (76%), whereas the HMDP cohort skewed toward Grade 3 (72%, p < 0.001). DPD was significantly associated with appendicular muscular uptake (ATTRwt: 84% vs. 38%, p < 0.001), creating a competitive “soft-tissue sink effect”. Conversely, HMDP demonstrated a unique predilection for pulmonary retention (ATTRwt: 68% vs. 46%, p = 0.008; ATTRv: 61% vs. 10%, p = 0.006). Visceral uptake was rare in ATTR but was a robust negative predictor strongly favoring AL amyloidosis (OR 0.016, p < 0.001).  Conclusions: [99mTc]Tc-DPD and [99mTc]Tc-HMDP possess distinct biodistribution profiles precluding direct interchangeability. HMDP maximizes myocardial contrast, whereas DPD provides a superior representation of the systemic musculoskeletal amyloid burden. Nuclear medicine physicians must adopt tracer-specific interpretive approaches to optimize non-invasive phenotyping.  Trial registration: not applicable.
SN  - 1619-7070
SN  - 1619-7089
ER  -