Biodistribution and imaging of 1-(2-deoxy-beta-d-ribofuranosyl)-2,4-difluoro-5-[123/125I]iodobenzene (dRF[(123/125)I]IB), a nonpolar thymidine-mimetic nucleoside, in rats and tumor-bearing mice.
1-(2-Deoxy-beta-D-ribofuranosyl)-2,4-difluoro-5-iodobenzene (dRFIB) is a putative bioisostere of iododeoxyuridine (IUdR). The advantages of dRFIB over IUdR for in vivo studies include resistance to both phosphorolytic cleavage of the nucleoside bond and de-iodination. dRFIB was radioiodinated (dRF(123/125)IB) by copper-catalyzed exchange using commercial sodium [(123/125)I]iodide. The in vivo biodistribution of dRF[(125)I]IB in BALBc mice and imaging of dRF[(123)I]IB in Sprague-Dawley rats are reported. In vivo data for rats show rapid clearance of radioactivity from blood (>95%ID in 15 minutes), extensive excretion in urine (56%ID/24 hours), concentration in the hepatobiliary-small intestine system and very little fecal excretion (approximately 3%ID/24 hours). Pharmacokinetic data for dRF[(125)I]IB (i.v. 48.7 ug/kg) in rats (t(1/2)[h] = 0.51 +/- 0.14, AUC(inf)[microg.min/mL] = 3.7 +/- 0.4, Cl[L/kg/h] = 0.75 +/- 0.12, Vss[L/kg] = 0.96 +/- 0.18) confirm previously reported dose-dependent pharmacokinetics. Scintigraphic images of rats dosed with dRF[(123)I]I were compatible with rapid soft-tissue clearance and extensive accumulation of radioactivity in bladder/urine and liver/small intestine. In tumor-bearing mice, thyroid and stomach radioactivity was indicative of moderate deiodination. An unidentified polar radioactive metabolite was detected in serum.
Stahlschmidt
Anke
A
PET Center, Radiopharmacy, Eberhardt-Karls Universitat Tubingen, Germany.
Khalili
Panteha
P
Sun
William
W
Machulla
Hans-Jürgen
HJ
Knaus
Edward E
EE
Wiebe
Leonard I
LI
D000818:Animals; D003853:Deoxyribonucleosides / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000175:diagnosis*; D011868:Radioisotopes / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D013936:Thymidine / Q000031:analogs & derivatives*
C483745:1-(2-deoxyribofuranosyl)-2,4-difluoro-5-iodobenzene; D003853:Deoxyribonucleosides; D011868:Radioisotopes; D013936:Thymidine