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

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.