GE HealthCare Flyrcado™ (Flurpiridaz F-18) PET MPI Performance

Challenge

Coronary artery disease remains the leading cause of death in the United States, requiring accurate noninvasive diagnostic methods to guide treatment decisions. Single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) has been the dominant modality in nuclear cardiology for decades, but faces significant limitations—particularly soft tissue attenuation artifacts that compromise diagnostic accuracy. These artifacts are especially problematic in women (where breast tissue causes anterior and lateral wall artifacts in up to 40% of studies) and patients with obesity, leading to false-positive results and unnecessary invasive procedures. Additionally, SPECT suffers from suboptimal first-pass myocardial extraction (65% for Rb-82, 82% for N-13 ammonia), lower spatial resolution, and radiation exposure of 10-20 mSv per study. Existing PET tracers like rubidium-82 and N-13 ammonia offer superior image quality but require on-site generators or cyclotrons, limiting widespread adoption. There was a critical need for a PET tracer that combined superior diagnostic performance with practical distribution logistics to expand access to high-quality cardiac imaging.

Approach

GE HealthCare developed Flyrcado™ (Flurpiridaz F-18), a novel fluorine-18-labeled PET myocardial perfusion imaging agent designed as a structural analog of pyridaben that binds to mitochondrial complex I with high affinity. The compound's mechanism leverages the high density of mitochondria in cardiac muscle (20-30% of myocardial intracellular volume) to achieve exceptional first-pass myocardial extraction of 94%—near the theoretical maximum. With a 110-minute half-life (over 10 times longer than existing cardiac PET tracers), Flurpiridaz can be manufactured at regional cyclotron facilities and delivered as ready-to-use unit doses, eliminating the need for on-site production infrastructure. The longer half-life also enables exercise stress testing with PET for the first time, providing the most robust protocol for evaluating ischemia.

Two pivotal clinical trials established the diagnostic efficacy and manufacturing feasibility of Flurpiridaz:

• Phase 3 AURORA Trial (GE265-303):
  

  • A multicenter, open-label study involving 730 patients with suspected coronary artery disease from 48 sites across the United States, Canada, and Europe (2018-2022).

  • All patients underwent one-day rest/stress Flurpiridaz PET and one- or two-day rest-stress Tc-99m SPECT before invasive coronary angiography (ICA), with images read by three blinded expert readers.

  • The primary efficacy endpoints were sensitivity and specificity of Flurpiridaz PET for detecting ≥50% coronary stenosis by quantitative ICA.

  • Of 578 evaluable patients (mean age 63.7 years; 32.5% women; 52.3% with BMI ≥30 kg/m²), Flurpiridaz PET demonstrated sensitivity of 80.3% versus 68.7% for SPECT (P=0.0003) and noninferior specificity of 63.8% versus 61.7% (P=0.0004).

  • Area under the receiver-operating characteristic curves was significantly higher for Flurpiridaz PET than SPECT in the overall population (0.80 vs 0.68; P<0.001), in women (0.84 vs 0.70; P=0.0091), and in obese patients (0.79 vs 0.67; P=0.0008).

  • Flurpiridaz PET was superior to SPECT for perfusion defect size/severity evaluation (P<0.001), image quality (P<0.001), diagnostic certainty (P<0.001), and radiation exposure (6.1±0.4 mSv vs 13.4±3.2 mSv; P<0.001).

• Manufacturing Comparison Study (GE265-001):
  

  • A descriptive, comparative, randomized, crossover study evaluating myocardial perfusion image quality using two manufacturing processes: high-performance liquid chromatography (HPLC) versus solid-phase extraction (SPE).

  • Conducted in 2022 to validate manufacturing scalability and ensure consistent image quality across different production methods.

  • Both manufacturing processes produced equivalent diagnostic-quality images, confirming the robustness of commercial production protocols.

‍Results: The Flurpiridaz F-18 (Flyrcado) development program successfully demonstrated superior diagnostic performance compared to the current standard of care, leading to FDA approval in September 2024:

• Superior diagnostic accuracy: 17% improvement in sensitivity over SPECT while maintaining comparable specificity, with particularly strong performance in historically difficult-to-image populations including women and patients with obesity.

• Dramatically improved image quality: Higher spatial resolution due to shorter positron range (1.0 mm vs 2.5 mm for Rb-82), enhanced contrast from 94% myocardial extraction, and superior diagnostic confidence reported by blinded readers.

• Reduced radiation exposure: Approximately 50% lower radiation dose compared to standard Tc-99m SPECT protocols (6.1 mSv vs 13.4 mSv).

• Expanded clinical access: Unit-dose delivery model eliminates need for on-site cyclotrons or generators, enabling cardiac PET in community hospitals and lower-volume imaging centers previously limited to SPECT.

• Exercise stress capability: 110-minute half-life enables the first practical combination of treadmill exercise stress with cardiac PET imaging, providing more robust functional assessment than pharmacologic stress alone.

• Manufacturing validation: Successful demonstration that both HPLC and SPE production methods yield equivalent image quality, ensuring reliable commercial-scale production.

These findings position Flurpiridaz F-18 as the first new myocardial perfusion radiopharmaceutical approved by the FDA in nearly 30 years, addressing a critical unmet need in cardiovascular diagnostics and marking a significant advancement in the field of nuclear cardiology.