Bone scintigraphy tracers have been widely recognized as useful diagnostic tools for transthyretin cardiac amyloidosis (ATTR-CA) and are now routinely used in clinical practice (1,2). Currently available bone scintigraphy agents include 99mTc-pyrophosphate (PYP), 99mTc-hydroxymethylene diphosphonate (HMDP), 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD), and 99mTc-methylene diphosphonate (MDP). Regarding 99mTc-MDP, Perugini et al. reported that all cases positive for 99mTc-DPD became negative when reexamined using 99mTc-MDP, suggesting that MDP is not suitable for diagnosing cardiac amyloidosis (3). In Japan, 99mTc-DPD is not commercially available, and only 99mTc-PYP and 99mTc-HMDP are currently approved for diagnostic evaluation of cardiac amyloidosis under the national health insurance system.
Kurisu et al. reported a highly instructive case of a 90-year-old man who underwent 99mTc-MDP bone scintigraphy for prostate cancer surveillance (4). Serial images obtained 16, 9, and 7 years earlier demonstrated a progressively increasing myocardial uptake, leading to the final diagnosis of ATTR-CA. The incidental discovery of cardiac tracer accumulation in a patient being followed up for prostate cancer represents a rare but important clinical clue. Although 99mTc-MDP is known to have low sensitivity for detecting ATTR-CA and is not recommended for diagnostic use, it can occasionally provide valuable information. Indeed, a previous report described the incidental identification of ATTR through MDP bone scans originally performed for prostate cancer staging (5).
Based on these findings, the clinical implications of this case are summarized as follows:
1. Detection of Progressive Changes over Time
The gradual increase in the myocardial uptake over the 16-year period demonstrated by serial MDP scans highlights an “incidental screening” function beyond the original purpose of the examination. Therefore, comparing prior bone scintigraphy images can be valuable for raising early suspicion of cardiac amyloidosis in daily clinical practice.
2. A Suggestive Finding: Myocardial Uptake Even with MDP
Although MDP is generally regarded as insensitive and not recommended for the detection of ATTR-CA, in this case, the cardiac uptake showed clear progression, indirectly reflecting disease development. This serves as a practical reminder that MDP is not entirely irrelevant for cardiac imaging. Nevertheless, the current consensus strongly recommends confirmatory evaluation with specific tracers (PYP, DPD, or HMDP) when their myocardial uptake is observed on MDP scans.
3. Implications for Early Detection and Intervention
The fact that a routine bone metastasis screening procedure led to the diagnosis of ATTR-CA underscores the clinical value of incidental findings in enabling early diagnosis and timely treatment initiation. In the era of disease-modifying therapies such as tafamidis, the early diagnosis of ATTR-CA has become increasingly crucial.
4. Diagnostic Considerations and Pitfalls
The myocardial uptake of 99mTc-MDP alone is insufficient to establish a diagnosis of ATTR-CA. Confirmation with dedicated bone tracers (PYP, DPD, or HMDP) is essential, along with serum and urine immunofixation, free light-chain assays, and TTR gene sequencing, to exclude AL amyloidosis and hereditary variants. Misinterpretation of the uptake of MDP can occur due to other causes, such as prior myocardial infarction, renal dysfunction, or nonspecific soft tissue accumulation, emphasizing the need for a careful differential diagnosis.
In summary, this case demonstrates that serial 99mTc-MDP bone scintigraphy, originally performed for surveillance of bone metastasis, revealed a progressive increase in the myocardial uptake over time, ultimately leading to a diagnosis of wild-type ATTR-CA. Particularly in elderly men presenting with conduction abnormalities or left ventricular hypertrophy suggestive of amyloidosis, careful review of prior bone scintigraphy to investigate the cardiac uptake or interval change may provide critical diagnostic clues.
When the uptake of MDP is observed in the myocardium, clinicians should not dismiss it as an artifact but instead proceed to confirmatory testing with PYP, DPD, or HMDP using planar and single photon emission computed tomography (SPECT) imaging. Advances in quantitative analysis techniques and SPECT/CT technology will improve the precision of myocardial tracer assessment. In the near future, quantitative evaluation of the cardiac uptake on bone scans may enhance the early detection of ATTR-CA. This instructive case by Kurisu et al. reinforces two important lessons: the diagnostic value of reviewing prior imaging studies, and the potential of incidental findings in routine clinical practice. Recognizing the subtle, progressive cardiac uptake on bone scintigraphy, even when obtained for other purposes, can lead to the timely diagnosis and treatment of transthyretin cardiac amyloidosis.
The author states that he has no Conflict of Interest (COI).
References
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