title: Elevated 18F-FDG levels in blood and organs after angiotensin II receptor blocker administration: experiment in mice administered telmisartan.
abstract: Angiotensin II receptor blockers (ARBs) are a common treatment for hypertensive patients but affect renal function. In this study, the effects of ARB on (18)F-FDG distribution and excretion were examined in mice treated with telmisartan at different doses.
  
  
  METHODS
  Male C57BL/6J mice were given telmisartan (low-dose group, 0.33 mg/kg/d; moderate-dose group, 0.66 mg/kg/d; high-dose group, 3 mg/kg/d) mixed in a high-fat diet for 20 wk. Mice on a telmisartan-free diet served as the control. At designated time points, the mice were injected with (18)F-FDG (18.5 MBq/mouse, n = 5-10/time point for each group) to examine its biodistribution. Autoradiography using kidney sections was performed to visualize (18)F-FDG excretion. Plasma blood urea nitrogen (BUN) and creatinine levels were also measured to evaluate renal function.
  
  
  RESULTS
  Twenty-week telmisartan treatment significantly and dose-dependently increased (18)F-FDG levels in the blood (percentage injected dose per gram of tissue normalized by animal body weight: low, 0.13 ± 0.03 [P < 0.0083]; moderate, 0.15 ± 0.01 [P < 0.0083]; high, 0.15 ± 0.03 [P < 0.0083], vs. control, 0.09 ± 0.01). Significantly increased (18)F-FDG levels in organs were observed in mice in the moderate- and high-dose groups but not in the low-dose group. The plasma BUN and creatinine levels also dose-dependently increased, but they were within the reference ranges (for BUN: low, 27.00 ± 4.42 mg/dL; moderate, 28.40 ± 2.70 mg/dL; high, 39.22 ± 6.91 mg/dL [P < 0.0083], vs. control, 22.40 ± 2.80 mg/dL. For creatinine: low, 0.28 ± 0.11 mg/dL; moderate, 0.40 ± 0.07 mg/dL [P < 0.0083]; high, 0.51 ± 0.09 mg/dL [P < 0.0083], vs. control, 0.18 ± 0.04 mg/dL). The blood (18)F-FDG level positively correlated with plasma BUN (r = 0.48, P < 0.01) and creatinine (r = 0.61, P < 0.01) levels. The (18)F-FDG levels in the blood and organs returned to baseline 3 wk after cessation of telmisartan treatment. Autoradiography indicated that renal (18)F-FDG excretion was attenuated by telmisartan treatment and was reversed after treatment cessation.
  
  
  CONCLUSIONS
  (18)F-FDG levels in the blood and organs were significantly increased by telmisartan treatment, indicating a potential increase in background activity on PET imaging of patients treated with ARBs. Our findings indicate the need for a careful assessment of (18)F-FDG uptake in patients treated with ARBs. A brief cessation of ARB treatment may be a potential method to avoid these effects and solve this problem.
authors.affiliation: Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Songji
authors.initials: S
authors.lastname: Zhao
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kuge
authors.forename: Nagara
authors.initials: N
authors.lastname: Tamaki
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D001565:Benzoates / Q000008:administration & dosage / Q000494:pharmacology*; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D019788:Fluorodeoxyglucose F18 / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011945:Receptors, Angiotensin / Q000378:metabolism*; D000077333:Telmisartan
chemical_list: D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001565:Benzoates; D011945:Receptors, Angiotensin; D019788:Fluorodeoxyglucose F18; D003404:Creatinine; D000077333:Telmisartan
keywords: 18F-FDG; ARB; renal function