Preclinical in vivo evaluation of [18]FACH in piglets: A new radiotracer for imaging of monocarboxylate transporters (MCTs)

Objective: Recently, we developed [18F]FACH as the first radiolabeled inhibitor of MCTs for potential tumor imaging (1). Encouraged by the very promising results in mice, showing the specific binding/transport of [18F]FACH in kidneys combined with high in vivo stability, herein we report on the biological evaluation of this radiotracer in piglets.

Methods: Biological evaluation was performed in 6 piglets (Landrace, 19.9±3.0 kg). The blocking experiments (n=3) were conducted using sodium α-cyano-4-hydroxycinnamate (α-CHC-Na, 25 mg/kg) administered i.v. 10 min prior to tracer application. The animals were anesthesized (ketamin/midazolam) and scanned by a SIEMENS Biograph mMR PET/MRI-system up to 60 min p.i. of 295±28 MBq [18]FACH via ear vein. The reconstructed list-mode PET-data were analyzed utilizing the PMOD Software. In vivo metabolite analysis was performed using plasma isolated from arterial blood samples (5, 15, 30, 45 and 60 min) and samples of homogenized kidney by semi-preparative radio-HPLC after deproteinization by ACN/H2O (9:1).

Results: In contrast to mouse, a rather fast metabolism of the radiotracer was observed in piglet. Five and 30 minutes after injection, the intact tracer was found to represent 50±13% and 12±6% of total plasma activity, respectively. Metabolite analysis revealed 48% of intact tracer in kidney cortex at 60 min p.i. Despite the fast metabolism, the PET scan results showed comparable selective kidney uptake of [18F]FACH in piglets as in mice. The blocking experiments revealed a reduction of this uptake to about 72% after pre-injection of α-CHC-Na.

Conclusion: The high kidney uptake of [18F]FACH obtained in both mice and piglets together with high inhibition by α-CHC-Na, specific inhibitor of MCT, provide evidence that the new MCT-targeting radiotracer could be proven in ongoing studies to be useful for imaging of MCTs expression with PET.