Comparison of Iodine-Labeled Sc-Fv-Fc Protein Biodistributions to Indium-Labeled Biodistributions in Nude Mice
V Kenanova1, T Olafsen1, A Wu1, P Yazaki2, L Williams2*, (1) UCLA, Los Angeles, CA, (2) City of Hope, Duarte, CASU-E-J-185 Sunday 3:00PM - 6:00PM Room: Exhibit Hall
Purpose: Animal biodistributions (BDs) are necessary to demonstrate radiopharmaceutical targeting. Radioiodine labeling requires considerably less novel agent material as compared to radiometal labeling. Yet iodine BDs show uptakes that are reduced in magnitude due to tissue metabolism and dehalogenation. It is important to measure the magnitude of this effect and thereby determine whether an iodine-BD could be converted mathematically into the comparable metal- BD. Methods: LS174T human colon tumors were implanted in nude mice. Simultaneous (I-125 and In-111) BDs were obtained using the H310A single-chain Fv-Fc antibody (105 kDa) fragment against CEA. Animals were sacrificed at 0, 2, 4, 6, 12, 24, 48 and 72 h post injection. Excised organs, tumor and blood were assayed for percent injected dose per gram of tissue (%ID/g). Curves were generated of %ID/g vs. time for liver, kidney, spleen, lungs, tumor and whole blood. In analogy with radiodecay, ratios of the iodine/indium BDs were fitted with single- exponential functions to determine initial halftimes of organ loss of iodine. Results: For solid tissues at time > 0, iodine-125 BD values were lower than the simultaneous In-111 BD. Hepatic results were the most dramatic with losses of nearly 90% of the iodine by 12 h into the study. For the colon tumor, there was a moderate decrease (approx. 50%) in the iodine BD as compared to the In-111 BD over 24 h. Blood showed no significant clearance difference between labels. Conclusions: Iodine losses for liver, kidneys, spleen and lungs could be described by initial T1/2 values of 1.3, 3.6, 3.5 and 10 h respectively. Tumor clearance (7 h) was comparable to lung. Liver was the most effective organ in removing iodine with similar but reduced effects seen in other solid tissues. No dehalogenation appeared in the blood out to 72 h.
Funding Support, Disclosures, and Conflict of Interest: Dept of the Army grants DAMD 17-00-1-203 and 17-00-1-0150 for Anna Wu