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Clinical Investigations |
1 Department of Psychiatry, Yale University School of Medicine and the Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut
2 Institute for Neurodegenerative Disorders, New Haven, Connecticut
123I-5-IA-85380 (123I-5-IA; [123I]-5-iodo-3-[2(S)-azetidinylmethoxy]pyridine) is a promising SPECT radiotracer for imaging ß2-containing nicotinic acetylcholine receptors (ß2-nAChRs) in brain. ß2-nAChRs are the initial site of action of nicotine and are implicated in various neuropsychiatric disorders. The feasibility and reproducibility of the bolus-plus-constant-infusion paradigm for equilibrium modeling of 123I-5-IA using SPECT in healthy nonsmokers was studied. Methods: Ten healthy nonsmokers (mean age ± SD, 43.7 ± 9.9 y) underwent two 123I-5-IA SPECT scans within 4 wk. 123I-5-IA was administered as a bolus (125.8 ± 14.6 MBq) plus constant infusion (18.1 ± 1.5 MBq/h). SPECT acquisitions (30 min) and venous blood sampling were performed every 60 min throughout the infusion (10–14 h). The test–retest variability and reliability of plasma activity (kBq/mL), the regional brain activity reflected by units of kBq/mL and %ID/mL (injected dose/mL brain tissue), and the equilibrium outcome measures VT' (ratio of total uptake to total plasma parent concentration) and VT (ratio of total uptake to free plasma parent concentration) were evaluated in 4 brain areas, including thalamus, striatum, cortex, and cerebellum. Results: Linear regression analysis revealed that time–activity curves for both plasma and brain 123I-5-IA activity stabilized by 5 h, with an average change of [2.5%/h between 6 and 8 h of infusion, permitting equilibrium modeling. The plasma free fraction (f1), total parent, and clearance demonstrated good test–retest variability (mean, 10.9%–12.5%), whereas the variability of free parent was greater (mean, 24.3%). Regional brain activity (kBq/mL) demonstrated good test–retest variability (11.1%–16.4%) that improved when corrected for infusion rate (mean, 8.2%–9.9%) or for injected dose (mean, 9.5%–13.3%). VT' demonstrated better test–retest variability (mean, 7.0%–8.9%) than VT (mean, 12.9%–14.6%). Reliability assessed by the intraclass correlation coefficient (ICC) was superior for kBq/mL (ICC = 0.83–0.90) and %ID/mL (ICC = 0.93–0.96) compared with VT' (ICC = 0.30–0.64) and VT (ICC = 0.28–0.60). The lower reliability of VT was attributed to the poor reliability of the free fraction (ICC = 0.35) and free parent (ICC = 0.68). Conclusion: These results support the feasibility and reproducibility of equilibrium imaging with 123I-5-IA for measurement of ß2-nAChRs in human brain.
Key Words: 123I-5-IA-85380 • SPECT • nicotinic acetylcholine receptor
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