RT Journal Article
SR Electronic
T1 First-in-Humans Evaluation of <sup>18</sup>F-SMBT-1, a Novel <sup>18</sup>F-Labeled Monoamine Oxidase-B PET Tracer for Imaging Reactive Astrogliosis
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1551
OP 1559
DO 10.2967/jnumed.121.263254
VO 63
IS 10
A1 Villemagne, Victor L.
A1 Harada, Ryuichi
A1 Doré, Vincent
A1 Furumoto, Shozo
A1 Mulligan, Rachel
A1 Kudo, Yukitsuka
A1 Burnham, Samantha
A1 Krishnadas, Natasha
A1 Bozinovski, Svetlana
A1 Huang, Kun
A1 Lopresti, Brian J.
A1 Yanai, Kazuhiko
A1 Rowe, Christopher C.
A1 Okamura, Nobuyuki
YR 2022
UL http://jnm.snmjournals.org/content/63/10/1551.abstract
AB Reactive gliosis, characterized by reactive astrocytes and activated microglia, contributes greatly to neurodegeneration throughout the course of Alzheimer disease (AD). Reactive astrocytes overexpress monoamine oxidase B (MAO-B). We characterized the clinical performance of 18F-(S)-(2-methylpyrid-5-yl)-6-[(3-fluoro-2-hydroxy)propoxy]quinoline (18F-SMBT-1), a novel MAO-B PET tracer as a potential surrogate marker of reactive astrogliosis. Methods: Seventy-seven participants—53 who were elderly and cognitively normal, 7 with mild cognitive impairment, 7 with AD, and 10 who were young and cognitively normal—were recruited for the different aspects of the study. Older participants underwent 3-dimensional magnetization-prepared rapid gradient-echo MRI and amyloid-β, tau, and 18F-SMBT-1 PET. To ascertain 18F-SMBT-1 selectivity to MAO-B, 9 participants underwent 2 18F-SMBT-1 scans, before and after receiving 5 mg of selegiline twice daily for 5 d. To compare selectivity, 18F-THK5351 studies were also conducted before and after selegiline. Amyloid-β burden was expressed in centiloids. 18F-SMBT-1 outcomes were expressed as SUV, as well as tissue ratios and binding parameters using the subcortical white matter as a reference region. Results: 18F-SMBT-1 showed robust entry into the brain and reversible binding kinetics, with high tracer retention in basal ganglia, intermediate retention in cortical regions, and the lowest retention in cerebellum and white matter, which tightly follows the known regional brain distribution of MAO-B (R2 = 0.84). More than 85% of 18F-SMBT-1 signal was blocked by selegiline across the brain, and in contrast to 18F-THK5351, no residual cortical activity was observed after the selegiline regimen, indicating high selectivity for MAO-B and low nonspecific binding. 18F-SMBT-1 also captured the known MAO-B increases with age, with an annual rate of change (∼2.6%/y) similar to the in vitro rates of change (∼1.9%/y). Quantitative and semiquantitative measures of 18F-SMBT-1 binding were strongly associated (R2 &gt; 0.94), suggesting that a simplified tissue-ratio approach could be used to generate outcome measures. Conclusion: 18F-SMBT-1 is a highly selective MAO-B tracer, with low nonspecific binding, high entry into the brain, and reversible kinetics. Moreover, 18F-SMBT-1 brain distribution matches the reported in vitro distribution and captures the known MAO-B increases with age, suggesting that 18F-SMBT-1 can potentially be used as a surrogate marker of reactive astrogliosis. Further validation of these findings with 18F-SMBT-1 will require examination of a much larger series, including participants with mild cognitive impairment and AD.