RT Journal Article
SR Electronic
T1 Cell-based assessment of radioiodinated immunoconjugate via a novel linker for enhancing residualizing power
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1128
OP 1128
VO 56
IS supplement 3
A1 Kim, Byoung Soo
A1 Kim, Eun Jung
A1 Choi, Dan Bee
A1 Choi, Tae Hyun
YR 2015
UL http://jnm.snmjournals.org/content/56/supplement_3/1128.abstract
AB 1128 Objectives As reported earlier, we have developed a new linker, (N-(4-isothiocyanatobenzyl)-2-(3-(tributyl stannyl) phenyl) acetamide (FCCS12026), for the preparation of more stable radioiodinated antibodies. Herein, we have evaluated utility of the FCCS12026 to cetuximab, an internalizing monoclonal antibody, on the aspect of target binding and internalizing characteristics.Methods [125I]-Cetuximab was prepared using the Chloramine T method. For indirect labeling of cetuximab, FCCS12026 was labeled with 125I by chloramine T to give, N-(4-Isothiocyanatobenzyl)-2-(3-[125I]phenyl)acetamide ([125I]-FCCS12027), and conjugated with cetuximab. Cell binding and internalization assays were performed in 6 cell lines (FaDu, H1376, A431, NCI-H727, NCI-H1299, NCI-H460). And the immunoreactive fraction was estimated from the cell binding data by the Lindmo method.Results [125I]-FCCS12027-Cetuximab had 1.8~4.5 fold higher specific binding values than [125I]-Cetuximab in 6 cell lines. Averaged immunoreactive fractions of [125I]-Cetuximab and [125I]-FCCS12027-Cetuximab were 0.4 and 0.7, respectively. The internalization ratio of [125I]-FCCS12027-Cetuximab was similar to that of [125I]-Cetuximab in each 6 cell lines.Conclusions All the results indicate that [125I]-FCCS12027-Cetuximab has great potential for specific radiolocalization and inactivation of tumor cells. Consequently, the use of a new linker might significantly improve the therapeutic efficacy and decrease in undesirable uptake of radiation to normal tissues during radioimmunotherapies.