Effects of anesthetic agents on cellular 123I-MIBG transport and in vivo 123I-MIBG biodistribution.
OBJECTIVE
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 (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 (123)I-MIBG 10 min after anesthesia with Ke/Xy, Ke, Xy, or Pb. Plasma NE levels and MIBG biodistribution were assessed.


RESULTS
Cellular (123)I-MIBG uptake was dose-dependently inhibited by Ke and Xy but not by Pb. Treatment for 2 h with 300 microM Ke, Xy, and Ke/Xy decreased uptake to 46.0 +/- 1.6, 24.8 +/- 1.5, and 18.3 +/- 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.


CONCLUSIONS
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.
Ko
Bong-Ho
BH
Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwondong, Kangnamgu, Seoul, South Korea.
Paik
Jin-Young
JY
Jung
Kyung-Ho
KH
Bae
Jun-Sang
JS
Lee
Eun Jung
EJ
Choe
Yearn Seong
YS
Kim
Byung-Tae
BT
Lee
Kyung-Han
KH
D019797:3-Iodobenzylguanidine / Q000493:pharmacokinetics*; D000777:Anesthetics / Q000008:administration & dosage*; D000818:Animals; D045744:Cell Line, Tumor; D004347:Drug Interactions; D008657:Metabolic Clearance Rate / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D009447:Neuroblastoma / Q000378:metabolism*; D009928:Organ Specificity; D010673:Pheochromocytoma / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution
D000777:Anesthetics; D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine