Vipivotide tetraxetan (PSMA-617)

PSMA-617 demonstrates high radiolytic stability for at least 72 h. A high inhibition potency (equilibrium dissociation constant Ki = 2.34 ± 2.94 nM on LNCaP; Ki = 0.37 ± 0.21 nM enzymatically determined) and highly efficient internalization into LNCaP cells are demonstrated.^[1]

The small-animal PET measurements show high tumor-to-background contrasts as early as 1 h after injection. In vivo distribution reveals specific uptake in LNCaP tumors and in the kidneys 1 h after injection. With regard to therapeutic use, PSMA-617 exhibits a rapid clearance from the kidneys from 113.3 ± 24.4 at 1 h to 2.13 ± 1.36 percentage injected dose per gram at 24 h. The favorable pharmacokinetics of the molecule leads to tumor-to-background ratios of 1,058 (tumor to blood) and 529 (tumor to muscle), respectively,24 h after injection.^[1]

• Cell lines

  PSMA-positive LNCaP cell line

• Concentrations

  0–5000 nM

• Incubation Time

  1 h

• Method

  The cell-based assay is performed using 10⁵ LNCaP cells/well. The radioligand (Glu-urea-Lys-(Ahx))₂-[⁶⁸Ga]Ga(HBED-CC)(19) is added as 0.75 nM solution to 12 different concentrations of non-labeled, ^natGa- or ^natLu-labeled PSMA-617 (from 0 to 5000 nM). After 1 hour incubation at 37 ℃, the cells are washed with ice-cold PBS and the cell-bound radioactivity is measured in a gamma counter.

• Animal Models

  8-wk-old BALB/c nu/nu mice which are subcutaneously inoculated into the right trunk with 5 × 10⁶ LNCaP cells in 50% Matrigel.

• Dosages

  ~30 MBq, 0.5 nM for small-animal PET imaging; ~1 MBq, 0.06 nM for organ distribution.

• Administration

  IV