RT Journal Article SR Electronic T1 In vitro residualization and binding of figitumumab radioimmunoconjugates JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1190 OP 1190 VO 55 IS supplement 1 A1 Collens, Sean A1 Forbes, John A1 Simms, Ryan A1 Wu, T. A1 Drewry, Joel A1 Hu, Meiduo A1 Stephenson, Karin A1 Burak, Eric A1 McCarthy, Timothy A1 Valliant, John YR 2014 UL http://jnm.snmjournals.org/content/55/supplement_1/1190.abstract AB 1190 Objectives Residualizing synthons for mAb radioiodination have been shown to increase radionuclide accumulation in tumours. Figitumumab (F) developed by Pfizer is a human mAb directed against the IGF-1 receptor (IGF-1R). F is known to be internalized and undergo lysosomal degradation. Biodistribution studies of F radioiodinated with standard synthons identified a need for improved tumour retention. A series of residualizing synthons were conjugated to F to evaluate their impact on radioiodine retention in vitro. Methods F was radioiodinated with 125-I by iododestannylation of SIB (non-residualizing control), SIPMB (negative-charged residualizing), or SGMIB (positive-charged residualizing) synthons followed by NHS-conjugation. 111In-DPTA labeling was performed by standard methods. Internalization/residualization and saturation binding assays were established to evaluate cellular radionuclide retention and binding affinity of F-conjugates using IGF-1R overexpressing A431 cells. Results Internalization studies demonstrated that 111In-DTPA-F and 125I-SIPMB-F provided the highest degree of residualization. At 24hrs post- internalization, cellular retention measured 54.6±1.2% and 43.5±0.6% of the initial intracellular activity. The balance of internalized activity was effluxed into the extracellular media. 125I-SGMIB-F offered little residualizing benefit (15.4±0.8%) compared to control 125I-SIB-F (7.5±1.1%). Kd values for all compounds ranged from 1.5 to 11.7 nM, similar to the reported binding affinity of native F. Conclusions 111In-DTPA- and 125I-SIPMB-F had greater residualizing properties compared to SGMIB and SIB iodinated conjugates. Negatively charged residualizing synthons for iodine radiolabeling promote better intracellular retention of activity, comparable to radiometals, than those with a positive charge when applied to F radioiodination.