Effects of anesthetic agents on cellular super(123)I-MIBG transport and in vivo super(123)I-MIBG biodistribution

• Published in: European journal of nuclear medicine and molecular imaging Vol. 35; no. 3; pp. 554 - 561
• Main Authors: Ko, Bong-Ho, Paik, Jin-Young, Jung, Kyung-Ho, Bae, Jun-Sang, Lee, Eun Jung, Choe, Yearn Seong, Kim, Byung-Tae, Lee, Kyung-Han
• Format: Journal Article
• Language: English
• Published: 01.03.2008
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-007-0605-0

Objectives: Small animal imaging with meta-iodobenzylguanidine (MIBG) allows characterization of animal models, optimization of tumor treatment strategies, and monitoring of gene expression. Anesthetic agents, however, can affect norepinephrine (NE) transport and systemic sympathetic activity. We thus elucidated the effects of anesthetic agents on MIBG transport and biodistribution. Methods: SK-N-SH neuroblastoma and PC-12 pheochromocytoma cells were measured for super(123)I-MIBG uptake after treatment with ketamine (Ke), xylazine (Xy), Ke/Xy, or pentobarbital (Pb). NE transporters were assessed by Western blots. Normal ICR mice and PC-12 tumor-bearing mice were injected with super(123)I-MIBG 10 min after anesthesia with Ke/Xy, Ke, Xy, or Pb. Plasma NE levels and MIBG biodistribution were assessed. Results: Cellular super(123)I-MIBG uptake was dose-dependently inhibited by Ke and Xy but not by Pb. Treatment for 2 h with 300 mu M Ke, Xy, and Ke/Xy decreased uptake to 46.0 plus or minus 1.6, 24.8 plus or minus 1.5, and 18.3 plus or minus 1.6% of controls. This effect was completely reversed by fresh media, and there was no change in NE transporter levels. In contrast, mice anesthetized with Ke/Xy showed no decrease of MIBG uptake in target organs. Instead, uptakes and organ-to-blood ratios were increased in the heart, lung, liver, and adrenals. Plasma NE was notably reduced in the animals with corresponding decreases in blood MIBG, which partly contributed to the increase in target organ uptake. Conclusion: In spite of their inhibitory effect at the transporter level, Ke/Xy anesthesia is a satisfactory method for MIBG imaging that allows favorable target tissue uptake and contrast by reducing circulating NE and MIBG.