Abstract
The accumulation of high levels of 99mTc-tetrofosmin (99mTc-TF) in the hepatobiliary system can lead to imaging artifacts and interference with diagnosis. The present study investigated the transport mechanisms of 99mTc-TF and attempted to apply competitive inhibition using a specific inhibitor to reduce 99mTc-TF hepatic accumulation. In this in vitro study, 99mTc-TF was incubated in HEK293 cells expressing human organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, OATP2B1, organic anion transporter 2 (OAT2), organic cation transporter 1 (OCT1), OCT2, and Na+-taurocholate cotransporting polypeptide with or without each specific inhibitor to evaluate the contribution of each transporter to 99mTc-TF transportation. In vivo studies, dynamic planar imaging, and single photon emission computed tomography (SPECT) experiments with rats were performed to observe alterations to 99mTc-TF pharmacokinetics using cimetidine (CMT) as an OCT1 inhibitor. Time–activity curves in the liver and heart were acquired from dynamic data, and the 99mTc-TF uptake ratio was calculated from SPECT. From the in vitro study, 99mTc-TF was found to be transported by OCT1 and OCT2. When CMT-preloaded rats and control rats were compared, the hepatic accumulation of the 99mTc-TF was reduced, and the time to peak heart count shifted to an earlier stage. The hepatic accumulation of 99mTc-TF was markedly suppressed, and the heart-to-liver ratio increased 1.6-fold. The pharmacokinetics of 99mTc-TF were greatly changed by OCT1 inhibitor. Even in humans, the administration of OCT1 inhibitor before cardiac SPECT examination may reduce 99mTc-TF hepatic accumulation and contribute to the suppression of artifacts and the improvement of SPECT image quality.
Highlights
No significant differences were apparent between the control group and the inhibition group in organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, OATP2B1, organic anion transporter 2 (OAT2), or Na+ -taurocholate cotransporting polypeptide (NTCP)
For organic cation transporter 1 (OCT1) and OCT2, the accumulated amount of 99m Tc-TF was decreased by competitive inhibition (p < 0.05)
Hara reported that the quality of cardiac Single photon emission computed tomography (SPECT) images of the inferior wall improved by drinking soda water before SPECT with the expansion of the gastric wall and by avoiding the reflux of bile containing high radioactivity [11], while Cherng reported that the liver excretion of 99m Tc-TF is accelerated by drinking lemon juice [12]
Summary
Coronary artery diseases are the leading cause of death in many developed countries. To decrease mortality and morbidity, signs need to be identified as early as possible. Single photon emission computed tomography (SPECT) is a useful diagnostic modality for cardiac disease because SPECT images can reflect cardiac function. Radiotracers for cardiac SPECT, such as 201 TlCl, 99m Tc-2-methyoxyisobutylisonitrile ( Tc-MIBI), 123 I-beta-methyl iodophenyl-pentadecanoic acid (123 I-BMIPP), and 3-123 Imetaiodobenzylguanidine (123 I-MIBG), are in widespread clinical use [1,2,3].
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