Cardiovascular

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

TL;DR

[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.

Key Findings

The multicenter retrospective cohort comprised 224 patients with confirmed ATTRwt, ATTRv, or AL amyloidosis who underwent late planar whole-body scintigraphy and targeted SPECT/CT with either DPD or HMDP.

  • DPD cohort: n = 109 (70 ATTRwt, 20 ATTRv, 19 AL).
  • HMDP cohort: n = 115 (90 ATTRwt, 13 ATTRv, 12 AL).
  • Inclusion required a final, confirmed diagnosis of ATTRwt, ATTRv, or AL amyloidosis.
  • Myocardial visual Perugini score (VISUAL_PS) and systemic extracardiac uptake (pulmonary, appendicular muscular, visceral, miscellaneous) were recorded.

In ATTRwt, the distribution of myocardial Perugini grades differed between tracers, with DPD predominantly Grade 2 and HMDP skewed toward Grade 3.

  • DPD cohort presented predominantly with Perugini Grade 2 (76%).
  • HMDP cohort skewed toward Grade 3 (72%, p < 0.001).
  • The authors conclude that HMDP maximizes myocardial contrast.

DPD was significantly associated with appendicular muscular uptake compared with HMDP in ATTRwt.

  • Appendicular muscular uptake in ATTRwt: 84% with DPD vs. 38% with HMDP (p < 0.001).
  • The authors describe this as creating a competitive 'soft-tissue sink effect'.
  • DPD is concluded to provide a superior representation of the systemic musculoskeletal amyloid burden.

HMDP showed a predilection for pulmonary retention compared with DPD in both ATTRwt and ATTRv.

  • ATTRwt: 68% with HMDP vs. 46% with DPD (p = 0.008).
  • ATTRv: 61% with HMDP vs. 10% with DPD (p = 0.006).

Visceral uptake was rare in ATTR but was a strong negative predictor of ATTR, favoring AL amyloidosis.

  • Odds ratio 0.016, p < 0.001 for visceral uptake as a negative predictor (strongly favoring AL).
  • Visceral uptake was rare in ATTR.

The two tracers have distinct biodistribution profiles that preclude direct interchangeability, requiring tracer-specific interpretation.

  • HMDP maximizes myocardial contrast, whereas DPD better represents systemic musculoskeletal amyloid burden.
  • The authors state nuclear medicine physicians must adopt tracer-specific interpretive approaches to optimize non-invasive phenotyping.

What This Means

This study compared two bone-scan tracers, DPD and HMDP, that are commonly used to detect transthyretin cardiac amyloidosis, a condition where abnormal protein builds up in the heart. The researchers reviewed scans from 224 patients at multiple centers who had a confirmed type of amyloidosis, and looked at both heart uptake and uptake elsewhere in the body. The two tracers behaved differently. HMDP tended to give stronger heart uptake (most wild-type patients scored at the highest grade) and was more often retained in the lungs. DPD more often showed uptake in the limb muscles, which may reflect a wider picture of amyloid in the musculoskeletal system but may also compete with heart uptake. Uptake in internal organs was uncommon in transthyretin amyloidosis but pointed strongly toward AL amyloidosis, a different type. This research suggests the two tracers cannot be treated as interchangeable, and that scans should be read with the specific tracer's patterns in mind. As a retrospective study, it shows associations and cannot establish which tracer is better for patients overall.

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Citation

Di Giorgio A, Battisti G, Bonazzi N, Prisco S, Starace M, Longhi S, et al.. (2026). The role of extracardiac radiotracer biodistribution in the evaluation of cardiac amyloidosis: a retrospective multicenter study on [99mTc]Tc-DPD and [99mTc]Tc-HMDP.. European journal of nuclear medicine and molecular imaging. https://doi.org/10.1007/s00259-026-08153-1