Pharmacokinetic studies and human dosimetry projections

RS Ravindra A. De Silva
MG Michael A. Gorin
RM Ronnie C. Mease
IM Il Minn
AL Ala Lisok
DP Donika Plyku
SN Sridhar Nimmagadda
MA Mohamad E. Allaf
XY Xing Yang
GS George Sgouros
SR Steven P. Rowe
MP Martin G. Pomper
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Animal experiments were performed in accordance with protocols approved by the Johns Hopkins Animal Care and Use Committee (ACUC). Bio-distribution studies for human dosimetry calculations used six-week-old female NOD/SCID mice (n = 25). Animals were sacrificed at 1, 4, 8, 24, and 48 h post-injection, with organs removed and processed as in Yang et al.8 Residence times for human organs, including bone marrow, heart, lungs, pancreas, spleen, brain, muscle, small intestine, liver, stomach, kidneys, and urinary bladder, were estimated from mouse bio-distribution data. Those data were used as input to Organ Level INternal Dose Assessment/EXponential Modeling (OLINDA/EXM)12 to obtain the absorbed organ dose for 111In and adult reference human male phantom. The residence time for the tumor was calculated assuming a tumor mass of 1 g using the same conversion from mouse to human.

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