Evaluation of meta-[211At]astatobenzylguanidine in an athymic mouse human neuroblastoma xenograft model.
A paired-label biodistribution was performed in athymic mice bearing SK-N-SH human neuroblastoma xenografts to compare the tissue uptake of meta-[211At]astatobenzylguanidine ([211At]MABG) and [131I]MIBG. Significantly higher (p < 0.05) uptake of [211At]MABG was seen in tumor (3.8 +/- 0.8% ID/g vs. 3.1 +/- 0.7% ID/g at 8 h) compared to [131I]MIBG. Desipramine reduced tumor uptake of [211At] MABG by 43%, suggesting that its accumulation was related to the specific uptake-1 mechanism. Higher uptake of [211At]MABG was also seen in normal tissue targets such as heart (6.0 +/- 0.9% ID/g vs. 4.5 +/- 0.8% ID/g at 8 h; p < 0.05). Pretreatment of mice with unlabeled MIBG increased tumor uptake of [211At]MABG by 1.5-fold while reducing uptake in heart and several other normal tissues. The vesicular uptake inhibitor tetrabenazine reduced heart uptake by 30% without reducing the tumor uptake. These results suggest such strategies might be useful for improving [211At]MABG tumor-to-normal tissue ratios.
Vaidyanathan
G
G
Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA. g405@acpub.duke.edu
Friedman
H S
HS
Keir
S T
ST
Zalutsky
M R
MR
D019797:3-Iodobenzylguanidine; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001246:Astatine; D004195:Disease Models, Animal; D005260:Female; D006146:Guanidines / Q000493:pharmacokinetics*; D006801:Humans; D007457:Iodine Radioisotopes; D007462:Iodobenzenes / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000378:metabolism*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D006146:Guanidines; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; C078685:1-(3-astatobenzyl)guanidine; D019797:3-Iodobenzylguanidine; D001246:Astatine