Adenosine SPECT imaging could single out neurodegenerative, psychiatric disorders

The neuromodulator adenosine and its interaction with a receptor known as A2A are being implicated in a range of brain diseases, including Parkinson’s and Huntington’s, as well as a spate of psychiatric disorders. A novel SPECT agent has been found to successfully shine a spotlight on this relationship, according to research published Aug. 22 in the Journal of Nuclear Medicine.

A group evaluated I-123 MNI-420 for the feasibility of imaging A2A in the brain. The research, led by Adriana Alexandre S. Tavares, a PhD candidate working with Molecular NeuroImaging, a neuroimaging research institute based in New Haven, Conn., is a continuation of scientific query into A2A in connection with dopaminergic receptors essential for controlled movement, and antagonists of the receptor have been found to have a protective effect on neurons in Parkinson’s studies. Additionally, A2A dysfunction may play a part in panic, hyperactivity and other mood disorders, schizophrenia and the physiology of addiction.

“Thus, in vivo imaging of A2A using SPECT or PET would enable studies investigating disease progression and treatment response in different psychiatric and neurodegenerative disorders,” wrote Tavares et al. “Furthermore, an A2A selective radiotracer would also be valuable in imaging studies evaluating therapeutics targeting A2A, such as drug occupancy studies, thereby providing a useful tool for the drug discovery process.”

A total of nine patients were enrolled in the study. Seven patients underwent I-123 MNI-420 brain SPECT imaging and tracer biodistribution and dosimetry was calculated using data from whole-body planar imaging performed on two patients. Researchers used simplified reference tissue models and Logan graphical analysis. Arterial blood and urine samples were also analyzed.

Findings of the study showed rapid uptake in the brain in an A2A-like pattern with particular tracer accumulation in the caudate and putamen. Best-case imaging was estimated at 90 minutes after injection and stable target-to-cerebellum ratios estimated from 1.4 to 2.0 and binding potentials from 0.8 to 1.2 according to different kinetic models. Results of this SPECT study were comparable to PET studies with another A2A targeting tracer, [7-methyl-C-11]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine (C-11 TMSX).

“The data indicate that I-123 MNI-420 is a useful SPECT radiotracer for imaging A2A in the brain and has radiation doses that would allow for multiple scans in the same research subject each year. The availability of I-123 MNI-420 offers the possibility of investigating A2A activity in specific conditions and evaluating drug occupancy for A2A candidate therapeutics.”