Synthesis of dendrimer-based biotin radiopharmaceuticals to enhance whole-body clearance.
To synthesize a biotin radiopharmaceutical that clears rapidly, dendrimer was used as a carrier and conjugated with succinimidyl 3-[(125)I]iodobenzoate and tetrafluorophenyl norbiotinamidosuccinate. Then, succinic anhydride was used to reduce its pI. In mice, the non-succinylated product showed high liver (67% ID/g) and kidney (44% ID/g) uptakes and whole-body retention (94% ID) at 20 min that persisted for 12 hr. The corresponding organ uptakes (22% and 11% ID/g) and the whole-body retention (47% ID) were drastically reduced by succinylation (p<0.0001). Lysine co-injection further lowered renal uptake.
Sato
Noriko
N
Nuclear Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
Park
Chang W
CW
Kim
Hyung-Sik
HS
Han
Eui-Sik
ES
Wong
Karen J
KJ
Paik
Ronald S
RS
Park
Luke S
LS
Yao
Zhengsheng
Z
Carrasquillo
Jorge A
JA
Paik
Chang H
CH
D000588:Amines / Q000737:chemistry / Q000493:pharmacokinetics* / Q000652:urine*; D000818:Animals; D041702:BALB 3T3 Cells; D001710:Biotin / Q000493:pharmacokinetics* / Q000652:urine; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000652:urine; D007463:Iodobenzoates / Q000737:chemistry / Q000493:pharmacokinetics* / Q000652:urine*; D007553:Isotope Labeling / Q000379:methods*; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism*; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D051379:Mice; D009928:Organ Specificity; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000652:urine; D014018:Tissue Distribution; D014915:Whole-Body Counting
D000588:Amines; D007457:Iodine Radioisotopes; D007463:Iodobenzoates; D019275:Radiopharmaceuticals; D001710:Biotin