Pharmacokinetic tissue distribution

MM Michael R. McDevitt
DT Daniel L. J. Thorek
TH Takeshi Hashimoto
TG Tatsuo Gondo
DV Darren R. Veach
SS Sai Kiran Sharma
TK Teja Muralidhar Kalidindi
DA Diane S. Abou
PW Philip A. Watson
BB Bradley J. Beattie
OT Oskar Vilhemsson Timmermand
SS Sven-Erik Strand
JL Jason S. Lewis
PS Peter T. Scardino
HS Howard I. Scher
HL Hans Lilja
SL Steven M. Larson
DU David Ulmert
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Biodistribution studies were conducted to evaluate the uptake and pharmacokinetic distribution of Zirconium-89 labeled hu11B6 ([89Zr]hu11B6) in human prostate cancer xenograft and GEM models. Mice received a single 5.55 MBq dose of [89Zr]hu11B6 (0.150 mCi of activity on 5–50 μg of protein) or a single 11.1 kBq dose of [225Ac]hu11B6 (300 nCi on 5 μg antibody) for injection via intravenous tail-vein injection (t = 0 h). Animals (n = 4–5 per group) were euthanized by CO2 asphyxiation at 4, 48, 120 and 360 h post-injection of [225Ac]hu11B6; or at 120 and 340 h post-injection of reporter [89Zr]hu11B6. Blood was immediately harvested by cardiac puncture. Tissues (including the tumor) were removed, rinsed in water, dried on paper, weighed, and counted on a gamma-counter using a 370–510 KeV window at secular equilibrium. Aliquots (0.020 mL) of the injected activities were used as decay correction standards and background signal was subtracted from each sample. The percentage of injected activit per gram of tissue weight (%IA/g) was calculated for each animal and data plotted as mean ± SD. Statistical analysis of data was performed using Prism software (Graphpad Software Inc, La Jolla, CA).

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