Pittsburgh compound B positron emission tomography detects cardiomyopathy in hereditary transthyretin amyloidosis patients with negative bone scintigraphy: a pilot study.

Abstract

Purpose: To evaluate the effectiveness of positron emission tomography (PET) with [¹¹C]-Pittsburgh Compound-B ([¹¹C]PiB) for detecting transthyretin amyloid (ATTR) cardiomyopathy in patients with transthyretin gene (TTR) variants associated with reduced bone scintigraphy sensitivity, and its ability to detect brain involvement in hereditary transthyretin amyloidosis.

Methods: This prospective case series included four hereditary ATTR amyloidosis patients with TTR variants associated with reduced bone scintigraphy sensitivity, and two patients with positive bone scintigraphy (one hereditary ATTR and one wild-type ATTR amyloidosis patient). All patients underwent diagnostic work-up at the Groningen Amyloidosis Centre of Expertise between April 2024 and March 2025, including [¹¹C]PiB PET/CT. Cardiac and brain [¹¹C]PiB uptake were assessed visually. Target-to-background ratios (TBRs) and cortical SUV ratios were calculated. TBR ≥1.09 was considered positive for ATTR cardiomyopathy and SUV ratios ≥0.7 was considered positive for brain involvement.

Results: Cardiac [¹¹C]PiB uptake was observed in three of four hereditary ATTR amyloidosis patients despite negative bone scintigraphy. In one of four patients, there was visually equivocal radiotracer uptake, but elevated TBRs did indicate ATTR cardiomyopathy. Conversely, both hereditary ATTR and wild-type ATTR amyloidosis patients with a positive bone scintigraphy had negative or inconclusive [¹¹C]PiB PET results. Brain uptake was observed in two asymptomatic patients, while no uptake was seen in two patients with suspected brain involvement.

Conclusion: [¹¹C]PiB PET could be an effective tool for detecting ATTR cardiomyopathy in patients with TTR variants associated with reduced bone scintigraphy sensitivity. However, its utility for detecting brain involvement in symptomatic hereditary ATTR patients remains uncertain.