Tissue distribution of intravenously administrated poly-arginine peptide R18D in healthy male Sprague–Dawley rats

Abstract

Aim: R18D is a poly-arginine peptide that has demonstrated neuroprotection in preclinical models of excitotoxicity, stroke, hypoxic-ischemic encephalopathy and traumatic brain injury. Here, we examined the peptide’s uptake in serum. Materials & methods: Healthy, male Sprague–Dawley rats were intravenously administered either 1000 nmol/kg R18D (D-enantiomer of R18) or approximately 2.5 nmol/kg (36 ± 9 MBq) [ ¹⁸F]R18D, for serum and organ tissue uptake, respectively. Serum samples underwent mass spectrometric analysis to detect unbound R18D peptide. Animals administered [ ¹⁸F]R18D were subjected to positron emission tomography imaging. Results & conclusion: Free R18D was detected at 5 min post-infusion in serum samples. [ ¹⁸F]R18D was rapidly distributed to the kidney (6–7%ID/g), and a small fraction localized to the brain (0.115–0.123%ID/g) over a 60-min acquisition period.

Lay abstract

R18D is a promising treatment for brain injury that has shown it can protect brain cells from damage in laboratory models of injury. These positive findings led us to examine what happens to R18D after administration in the body. Healthy, male rats were given 1000 nmol/kg R18D or approximately 2.5 nmol/kg (36 ± 9 MBq) [ ¹⁸F]R18D via an injection. Chemical and imaging analyses measured the amount of each compound. Free R18D was present in the blood 5 min after administration and was quickly absorbed by the kidney (6–7%ID/g) and brain (0.115–0.123%ID/g) within 60 min.