18F-Nifene for quantification of α4β2 nicotinic receptors
Introduction
2-[18F]Fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine, 18F-Nifene (agonist), is a high affinity (Ki = 0.50 nM) radiotracer for the α4β2 nicotinic receptors. The radiotracer has a unique 3-pyrrolinyl ring structure and obtained by labeling of nitro precursor with 18F-fluorine followed by de-protection of N-BOC group. 18F-Nifene has been shown to bind rat and monkey brain regions rich in α4β2 nicotinic receptors with faster binding profile in monkey PET studies [1]. In order to quantify the binding of 18F-Nifene in brain, we used Inveon MicroPET imaging and ex vivo autoradiographic studies.
Section snippets
Methods
Male Sprague Dawley rats (200–250 g) were anesthetized with halothane and injected with 18F-Nifene (~ 11 MBq). The animals were allowed to recover from anesthesia and had free access to food and water. They were sacrificed at 60 min after injection and the brain samples were collected. The first set of rat brains were sectioned sagittally (20 μm thick), mounted on a glass slide and then air dried and apposed to phosphor screens overnight. The screens were read by Cyclone Phosphor Imaging systems
Results
18F-Nifene binding to thalamic and extrathalamic brain regions was consistent with the α4β2 nicotinic receptors distribution in rat brain measured in vitro studies. The least binding was seen in cerebellum (Ce) regions. Rat ex vivo 18F-Nifene binding ratios in autoradiographic studies were measured using Ce and corpus callosum (CC) as reference regions, where Th/Ce, Co/Ce, Th/CC and Co/CC were found to be 3.7, 2.1, 4.6 and 2.6 respectively. Rat ex vivo 18F-Nifene binding ratios in MicroPET
Conclusion
Ex vivo autoradiographic and MicroPET studies revealed that 18F-Nifene binding to thalamic and extrathalamic regions in the rat brain.
Fig. 1. Ex vivo rat brain with 18F-nifene. (A) MicroPET images showing binding in thalamus (Th) and lower binding in cortex (Co) and subiculum (Su) and least binding in cerebellum (Ce). (B) Sections in the optical scan to reveal brain regions. (C) 20 μm sections showing binding in Th, Co and Su and least binding in Ce and corpus callosum (CC).
[1] Pichika, et al.
Acknowledgment
Research Support NIH R01AG029479-01A1.