Publikationsrepositorium - Helmholtz-Zentrum Dresden-Rossendorf

Aim: The lipophilic cationic Ga‐68‐complex (Tsang B.W. et al. J Nucl Med 1993; 34; 1127) of Tris(4,6‐dimethoxysalicylaldimine)‐N,N′‐bis(3‐aminopropyl)‐N,N′‐ethylenediamine (BAPEN), showed high accumulation in mice hearts (Nucl Med Biol 2010; 37; 149). To reevaluate the radiopharmacological profile in rats the Ga‐68‐BAPEN was produced by a kit formulation and the biodistribution, kinetics and metabolism were studied with small animal PET.
Materials & methods: The BAPEN was labeled with 0.1 M HCl Ga‐68‐Cl3 (generator eluate 1 M HCl) in a one step procedure. Before application human serum albumin was added to a final concentration of 1%, and the solution filtrated (22 μm pore size). The biodistribution at 5 and 60 min p.i. (each time point 8 rats) after single intravenous injection, arterial blood clearance over 1 h (n=2), and the in vivo metabolism in Wistar rats were investigated in combination with small animal PET, and the main biokinetic parameters of Ga‐68‐BAPEN were estimated.
Results: Ga‐68‐BAPEN was prepared with purity >91% within 20 min. The activity was fast accumulated in the rat heart (values in SUV; 5 min p.i., 1.56 ± 0.19; 60 min, 1.42 ± 0.35) with the following heart‐to‐tissue ratios at 5 min p.i.: blood 4.2, lung 2.2, liver 0.4, kidneys 0.3, and brain 109.6. No clearance of Ga‐68‐activity from the heart was observed over 1 hour. The arterial blood clearance of the original compound was biphasic with half lifes of 2 min and 23 min respectively; it was metabolized with a half‐life of 1.6 min. The Ga‐68‐activity was rapidly excreted into the intestine (5 min p.i. 34.9 ± 4.0%ID; 60 min p.i. 56.7 ± 7.0%ID).
Conclusion: Ga‐68‐BAPEN showed a typical perfusion dependent biodistribution pattern in rats, with high accumulation in heart, kidneys, liver, adrenals, and pancreas. The heart was clearly delineated with low background. The increasing liver uptake could complicate the quantitative imaging of the heart apex at late time points. Ga‐68‐BAPEN was fast distributed followed by a slow blood clearance on a low activity level. The fast in vivo metabolism of the Ga‐68‐BAPEN in rats prevented a more distinct perfusion dependent biodistribution pattern. No transport through the blood‐brain‐barrier into the brain was observed. The Ga‐68‐BAPEN may be useful as radiopharmaceutical for perfusion imaging, particularly, for the heart.