Radiation dosimetry and biodistribution of the beta-amyloid plaque imaging tracer 11C-BTA-1 in humans

Abstract

SummaryAim: [N-methyl-11C]2-(4'-(methylaminophenyl)-benzothiazole (11C-BTA-1) is a thioflavin-T derivative that has been one of the promising PET tracers for imaging of amyloid plaque distribution in the Alzheimer patients brain in vivo. The biodistribution and dosimetry of this tracer in humans is presented and compared to the results of a previous dosimetry and biodistribution study of another thioflavin-T derivative [N-methyl-11C]2-hydroxy-(4'-(methylaminophenyl)- benzothiazole (11C-OH-BTA-1) in baboons. Methods: Five subjects underwent 2D dynamic PET imaging. Source organs were segmented using a semiautomatic algorithm based on clustering. Residence times for each source organ were determined by analytical integration of an exponential fit of the time activity curves. Finally organ doses were estimated using the software OLINDA/EXM. Results: The administration of 286 ± 93 MBq 11C-BTA-1 was well tolerated by all subjects. Effective radiation dose was 4.3 μSv/MBq, range 3.6–5.0 μSv/MBq. In four of the five subjects the liver, in one of the subjects the gallbladder was the critical organ. Conclusion: The radiation burden of a single dose of 300 MBq 11C-BTA-1 is within the accepted limits for research purpose. In contrast to the previous non-human primate study revealing the gallbladder as the critical organ for 11C-6-OH-BTA-1, we found the liver as the critical organ in humans using 11C-BTA-1. Possible explanations may be (1) a reduced bile concentration of 11C-BTA-1 due to the absent OH-group or (2) a different hepatic metabolism of thioflavin derivatives in human and baboon.

Simulation study comparing the helmet-chin PET with a cylindrical PET of the same number of detectors

“…The outside FOV (oFOV) activity is 4 times higher than that of the inside FOV (iFOV) activity. The activity distribution is roughly estimated based on the tracer for amyloid imaging (Thees et al 2007) at a specific time from the time activity curves. The ratio consideration mainly accounts for organs which had a higher activity distribution than other parts of the body.…”

“…PET enables non-invasive mapping of in vivo neurobiological functions such as blood flow, metabolism, and receptor binding (Tai and Piccini 2004). The development of several tracers for amyloid imaging (Scheinin et al 2007, Thees et al 2007, Shidahara et al 2013 and tau imaging (Maruyama et al 2013, Harada et al 2016, Johnson et al 2016 makes it possible to use PET for early diagnosis of Alzheimer's disease and to obtain spatiotemporal information on the progression of the disease. To attain the best treatment efficacy and widen the application of PET scanners, it is important to achieve low cost PET scanners with high sensitivity and high spatial resolution.…”