Nature review article: PET Radiotracers used in cerebrovascular PET studies

Cerebrovascular disease encompasses a range of pathologies that affect different components of the cerebral vasculature and brain parenchyma. Large artery atherosclerosis, acute cerebral ischaemia, and intracerebral small vessel disease all demonstrate altered metabolic processes that are key to their pathogenesis. Positron Emission Tomography (PET) can detect and quantify metabolic processes that are relevant to each facet of cerebrovascular disease. The review article published in the November 2017 issue of Nature Reviews Neurology describes how PET-based imaging of metabolic processes at the neurovascular interface has contributed to our understanding of cerebrovascular disease.

Evans, N. R. et al. PET imaging of the neurovascular interface in cerebrovascular disease. Nat Rev Neurol 13, 676–688 (2017). doi:10.1038/nrneurol.2017.129

PET imaging employs various radioligands to detect physiological processes in vivo. The article written by Nicholas R. Evans, University of Cambridge, Cambridge, UK and his colleagues summaries the radioisotopes of PET ligands used for the following list of cellular or physiological targets of vascular biology, actute ischaemic stroke and small vessel disease:

1. Increased metabolic rate (inflammation): ¹⁸F-FDG
   2. Macrophages: ⁶⁸Ga-DOTATATE (targeting somatostatin receptor type 2)
   3. Microcalcification: ¹⁸F-NaF (hydroapatite)
   4. Hypoxia: ¹⁸F-FMISO (targeting selective reduction in hypoxia)
   5. Macrophages and microglia: ¹¹C-PK11195, ¹¹C-PBR28, ¹⁸F-DPA-714, ¹¹C-vinpocetine, ¹⁸F-GE-180 (all targeting TSPO)
   6. Neurons: ¹¹C-FMZ (GABA-A receptor)
   7. Amyloid: ¹¹C-PiB (analogue of thioflavin T)
   8. Neurons: ¹⁸F-FNDP (epoxide hydrolase enzyme)
   9. Expressed on neurons, astrocytes, microglia and endothelial cells: ¹⁸F-NS14490 (α7 nicotonic acetylcholine receptor)
   10. Apoptosis: ¹⁸F-labeled isatins (caspase 3, caspase 7)

The review article considers sensitivity, specificity, technical considerations and also clinical implications for each radiotracersThe nanoScan PET/MRI3T is an ideal combination of modalities for research of cerebrovascular diseases: structural imaging provided by MRI is co-registered and combined with the PET ability to detect and quantify these pathophysiological processes in vivo. Information obtained from PET studies has helped to shape the understanding of key concepts in cerebrovascular medicine, including vulnerable atherosclerotic plaque, salvageable ischaemic penumbra, neuroinflammation and selective neuronal loss after ischaemic insult. New PET ligands continue to be developed that have superior specificity or that target new processes of interest.