Evaluation of first-pass extraction fraction of [¹⁸F]labeled fluoroalkylphosphonium salts in isolated rat heart: Comparison with [¹³N]NH₃

Objectives Despite substantial advances in the diagnosis of cardiovascular diseases, there is a few option of PET radiopharmaceuticals for diagnosis of ischemic heart diseases. Thus, three kinds of ¹⁸F-labeled phosphonium cation derivatives, [¹⁸F]fluoroalkylphosphonium salts ([¹⁸F]FATPs) were synthesized which were accumulated in myocardium. Here, we compared and analyzed the first-pass extraction fraction value (EF) and microPET images of each [¹⁸F]FATP with [¹³N]NH₃.

Methods The EF of the [¹⁸F]FATPs ([¹⁸F]FPTP, [¹⁸F]FHTP, [¹⁸F]FETP) and [¹³N]NH₃ were measured in isolated rat hearts perfused with the Langendorff method (flow velocities: 0.5, 4.0, 8.0, 16.0 ml/min, n >6, each compound and each velocity). Normal rats were imaged with microPET for 30 min after i.v. injection of 37 MBq of [¹⁸F]FATPs and [¹³N]NH₃.

Results The EF of [¹⁸F]FATPs was over 30% at 0.5 ml/min respectively and [¹⁸F]FATPs showed higher EF than [¹³N]NH₃ in 4.0, 8.0, 16.0 ml/min (Table 1). The heart-to-lung, heart-to-liver ratios of [¹⁸F]FPTP, [¹⁸F]FHTP, [¹⁸F]FETP, [¹³N]NH₃ were 5.47 ± 0.54, 6.41 ± 0.58, 6.01 ± 0.82, 2.08 ± 0.49 and 2.53 ± 0.31, 3.85 ± 0.11, 3.03 ± 0.76, 0.62 ± 0.04 respectively at 10 min after injection indicating that [¹⁸F]FATPs are optimal cardiac imaging agents.

Conclusions [¹⁸F]FATPs showed higher EF, more stable uptake in the myocardium and more rapid clearance from liver or lung than [¹³N]NH₃, that could lead to excellent image quality. [¹⁸F]FATPs might have a potential to be utilized as a novel myocardial agent for cardiac PET/CT applications.