Role of Nuclear Medicine in Amyloidosis
Amyloid is made of misfolded protein fibrils that deposit in tissues, and the protein that forms the fibrils determines the type of amyloidosis. The main established nuclear medicine role is diagnosing cardiac ATTR. Other studies can image amyloid deposits, but have more limited use.
The types
| Type | Deposited protein | Main point |
|---|---|---|
| AL (light-chain) | Immunoglobulin light chains | Often affects several organs, including the heart, kidneys and nerves |
| ATTR (transthyretin) | Transthyretin | Often affects the heart; may be wild-type or hereditary |
| AA (amyloid A) | Serum amyloid A | Associated with chronic inflammation; commonly affects the kidneys |
What can be imaged
| Radiopharmaceutical | Main use | Key limitation |
|---|---|---|
| 99mTc-PYP (pyrophosphate), DPD or HMDP | Detect cardiac ATTR | Confirm uptake in the heart muscle with SPECT or SPECT/CT |
| 123I-serum amyloid P | Map systemic deposits, especially AL and AA | Specialised test; poor assessment of the heart |
| 18F-florbetapir or florbetaben PET | Detect cardiac amyloid in AL and ATTR | Specialised or investigational; does not reliably identify the type |
Perugini grading
Perugini grading compares heart-muscle uptake of a 99mTc bone tracer with rib uptake:
| Grade | Finding |
|---|---|
| 0 | No heart-muscle uptake |
| 1 | Less uptake than ribs |
| 2 | Uptake equal to ribs |
| 3 | More uptake than ribs, often with reduced visible bone uptake |
The diagnostic rule
- Grade 2 or 3 uptake can establish cardiac ATTR without a biopsy only when tests for a monoclonal protein are negative.
- Those tests are serum free light chains, and serum and urine immunofixation.
- If the screen is positive, or the scan is uncertain, further assessment is needed — often a biopsy to identify the amyloid type.
- After ATTR is diagnosed, TTR genetic testing distinguishes hereditary from wild-type disease.
Pitfalls
- Blood-pool activity or overlapping ribs can mimic heart uptake.
- Bone-tracer scans are not established for routine treatment-response monitoring.
Fuller version, with the criteria in detail: Cardiac amyloidosis.
Take home
- The established role is diagnosing cardiac ATTR; the other studies image deposits and have more limited use.
- Grade 2 or 3 uptake establishes cardiac ATTR without biopsy only when the monoclonal protein screen is negative.
- Confirm that the uptake is in the heart muscle with SPECT or SPECT/CT — blood pool and overlapping ribs mimic it.
Sources
- Gillmore JD, Maurer MS, Falk RH, et al. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation. 2016;133(24):2404-12.
- Perugini E, Guidalotti PL, Salvi F, et al. Noninvasive etiologic diagnosis of cardiac amyloidosis using 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy. J Am Coll Cardiol. 2005;46(6):1076-84.
- Dorbala S, Ando Y, Bokhari S, et al. ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: part 2 of 2, diagnostic criteria and appropriate utilization. J Nucl Cardiol. 2020;27(2):659-73.
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