Key result
Tc-DPD and Tc-HMDP exhibit distinct uptake patterns in wild-type ATTR, differing in muscular and cardiac retention.
Why the study?
Although bone scintigraphy with [99mTc]Tc-DPD or [99mTc]Tc-HMDP is a non-invasive cornerstone for diagnosing ATTR-CA, the interchangeability of these tracers and the clinical relevance of systemic extracardiac uptake remain poorly defined.
Does bone scintigraphy with [99mTc]Tc-DPD compared to [99mTc]Tc-HMDP result in different myocardial visual grading and systemic extracardiac biodistribution profiles in patients with confirmed cardiac amyloidosis?
Cohort (n=224)
Blinded reader evaluation
Yes
Does bone scintigraphy with [99mTc]Tc-DPD compared to [99mTc]Tc-HMDP result in different myocardial visual grading and systemic extracardiac biodistribution profiles in patients with confirmed cardiac amyloidosis?
[99mTc]Tc-DPD and [99mTc]Tc-HMDP exhibit distinct whole-body biodistribution profiles in cardiac amyloidosis—with DPD causing a muscular 'soft-tissue sink' that lowers Perugini grading and HMDP showing higher pulmonary retention and myocardial contrast—precluding their direct interchangeability and necessitating tracer-specific interpretation.
Distinct DPD/HMDP biodistributions may require tracer-specific Perugini thresholds; leaves open standardization of bone scintigraphy in ATTR amyloidosis.
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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Giorgio et al. (2026) conducted a cohort in Cardiac amyloidosis (ATTRwt, ATTRv, and AL amyloidosis) (n=224). [99mTc]Tc-DPD bone scintigraphy (or Perugini visual score >=2 in multivariable model) vs. [99mTc]Tc-HMDP bone scintigraphy was evaluated on Prediction of ATTR cardiac amyloidosis diagnosis (vs. AL amyloidosis) using Perugini visual score >= 2 (OR 30.49, 95% CI 8.16-113.93, p=<0.001). [99mTc]Tc-DPD and [99mTc]Tc-HMDP showed distinct biodistributions in ATTRwt, with DPD favoring muscular uptake (84% vs 38%, p<0.001) and HMDP favoring Perugini Grade 3 (72% vs 21%, p<0.001).
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