Piflufolastat ¹⁸F

Prostate-Specific Membrane Antigen (PSMA), is a trans-membrane glycoprotein primarily expressed in normal human prostate epithelium at low levels, but may be overexpressed by malignant tissues, particularly by prostate cancer cells, including metastatic disease. Fluorine (¹⁸F) is a β+ emitting radionuclide that enables positron emission tomography. Piflufolastat (¹⁸F) is a selective secondgeneration fluorine-18-labeled small-molecule PSMA inhibitor. Based on the intensity of the signals, PET images obtained using piflufolastat (¹⁸F) indicate the presence of PSMA expressing tissues.

At the chemical concentrations used for diagnostic examinations, this medicinal product does not appear to have any pharmacodynamic activity.

Distribution

Blood levels decline in a biphasic fashion. The distribution half-life is 0.17 ± 0.04 hours and the elimination half-life is 3.47 ± 0.49 hours.

Organ uptake

Physiologic accumulation of piflufolastat (¹⁸F) is observed in the kidneys (16.5% of administered activity), liver (9.3%), and lung (2.9%), within 60 minutes of intravenous administration. Most of the remaining 70% of activity at 60 minutes is with the rest of the body background region.

Elimination

The only radioactive component detected in plasma samples by high-performance liquid chromatography (HPLC) up to 173 minutes post-injection was unchanged piflufolastat (¹⁸F). Elimination is by urinary excretion. In the first 8 hours post-injection, approximately 50% of administered radioactivity is excreted in the urine.

Half-life

The biological and effective half-life of piflufolastat (¹⁸F) are 3.47 ± 0.49 hours and approximately 70 minutes, respectively.

Renal / Hepatic impairment

The pharmacokinetics in patients with renal or hepatic impairment have not been characterised

An extended single dose toxicity study was conducted in rats with the non-radioactive pharmaceutical. No adverse reactions were observed in any of the animals, and no deaths occurred at the highest tested dose of 0.5 mg/kg. This dose is over 875-fold higher than the maximum clinical dose of 40 µg/patient (or 0.5714 µg/kg for a reference body weight of 70 kg); on a body surface area basis, this dose is approximately 142-fold higher, suggesting adequate safety margin.

No other studies were conducted.

This medicinal product is not intended for regular or continuous administration. At the chemical concentrations and the activities used for diagnostic examinations, additional studies does not appear to be necessary.