Tc-99m-PYP⁹⁹ᵐTc-pyrophosphate

Quick Answer

Tc-99m-pyrophosphate (PYP) is a bone-avid tracer that localizes to transthyretin (ATTR) cardiac amyloid deposits, enabling noninvasive diagnosis when a monoclonal protein is excluded. Positivity is graded by the Perugini visual score (0–3) and the heart-to-contralateral (H/CL) ratio, with SPECT mandatory to confirm myocardial (not blood-pool/bone) uptake. In Europe, DPD/HMDP are the equivalent bone tracers.

Mechanism

PYP binds microcalcifications associated with amyloid fibrils (the exact mechanism is incompletely understood), with greater uptake in ATTR than AL amyloid — though AL can still be avid, which is why the monoclonal screen is mandatory. It is also a hydroxyapatite-seeking bone agent (hence rib/sternal uptake to reference against).

Biodistribution

Bone (ribs, sternum, spine), blood pool early, and — in disease — myocardium. Imaging at 1 hour (± 3 hours), when blood-pool activity has cleared further.

Clinical Indications

• ATTR cardiac amyloidosis — the dominant modern use (see the cardiac amyloidosis disease page for the full diagnostic algorithm).
• (Historical) acute myocardial-infarction imaging; some soft-tissue/vascular-calcification settings.

Protocol

1. Screen for a monoclonal protein (serum/urine immunofixation + serum free light chains) — first or in parallel; not optional.
2. Inject Tc-99m-PYP; image at 1 h (± 3 h).
3. Acquire planar + SPECT (or SPECT/CT) — SPECT required to prove myocardial (not blood-pool/rib) uptake.
4. Grade (Perugini 0–3) and quantify (H/CL ratio).

Interpretation & Grading

• Perugini 0 (none), 1 (< rib), 2 (= rib), 3 (> rib, faint bone) — grade 2–3 with a negative monoclonal screen is highly specific for ATTR.
• H/CL ratio ≥ 1.5 at 1 h (or ~1.3 at 3 h) supports ATTR.
• SPECT confirmation is decisive when planar/quantitative results are borderline or blood pool is retained.

Reporting Checklist

• Perugini grade, H/CL ratio (with timing), and explicit SPECT confirmation of myocardial uptake.
• Monoclonal-screen result (a positive-uptake scan is not ATTR-diagnostic without it).
• Note blood-pool retention, rib overlap, or prior-MI calcification if present.

Common Pitfalls

• Blood-pool activity on early/planar images mimicking myocardial uptake.
• Rib/sternal overlap misread as cardiac uptake on planar views.
• Skipping the plasma-cell-dyscrasia workup (mislabeling AL as ATTR).
• Early-imaging blood-pool retention (renal failure) inflating apparent uptake.

Board Pearls

A positive PYP scan diagnoses ATTR cardiac amyloidosis only after a monoclonal protein is excluded (serum/urine immunofixation + serum free light chains) — AL amyloid can also take up bone tracer, and missing a plasma-cell dyscrasia risks a dangerous misdiagnosis.

SPECT is mandatory to confirm uptake is truly myocardial rather than residual blood pool or overlying rib — the classic planar false positives.

Grade with the Perugini visual score (0–3) relative to rib/bone and the H/CL ratio (≥ 1.5 at 1 h; ~1.3 at 3 h). Grade 2–3 + negative monoclonal screen is highly specific (Gillmore, > 99%) for ATTR — establishing the diagnosis without biopsy. PYP historically imaged acute MI, but ATTR is its dominant modern use (DPD/HMDP are the European equivalents).

Related Pages

• Disease: Cardiac amyloidosis (ATTR) — full diagnostic algorithm and therapy.
• Related: Nuclear cardiology overview; pitfalls: Pearls, pitfalls & normal variants.

Figure / Diagram Suggestions

• A PYP diagnostic algorithm (uptake + monoclonal screen → ATTR vs biopsy).
• The Perugini 0–3 grading plate (cardiac vs rib uptake).
• A planar-vs-SPECT teaching pair (blood-pool mimicry resolved by SPECT).

Self-Check (Board-Style)