Pretargeted dual-modality (SPECT/fluorescence) imaging in a carcinoembryonic antigen-expressing tumor model

Objectives Intraoperative tumor detection with specific radiotracers is a useful tool for accurate localization and resection during surgery. These techniques could benefit from the addition of an optical tracer, since this may allow more accurate intraoperative delineation of the tumor. Both tracers in such a dual modality approach need to show a high specificity and tumor-to-background ratio (TBR). We investigated the potential of a pretargeting system using the anti-CEACAM5 x anti-HSG (histamine-succinyl-glycine) bispecific antibody TF2, and a new hapten-peptide (RDC-018) derived from IMP288, bearing both DOTA for radiolabeling and a fluorescent moiety (IRdye800CW). In this study, we assessed the radiolabeling, in vivo biodistribution and tumor localization properties of RDC-018 in a pretargeting setting compared to IMP288.

Methods Three groups of BALB/c nude mice bearing s.c. CEA-expressing LS174T human colonic tumors (left flank) and CEA-negative SK-RC-52 human renal cell tumors (right flank) were injected with saline or with TF2 (0.6 or 6 nmole), and then after 16 h, a 0.05x molar equivalent of either ¹¹¹In-labeled IMP288 or ¹¹¹In-labeled RDC-018 was administered. Mice were euthanized 2 and 24 hours p.i. (5 mice/group) and optical images were acquired using an IVIS Lumina system and organs of interest were dissected and counted in a gamma counter.

Results The biodistribution of the dual-label hapten peptide showed specific CEA-expressing tumor targeting (LS174T: 22.0 and 10.0 %ID/g, SK-RC-52: 6.0 and 0.9 %ID/g at 2 h and 24 h p.i., respectively) and clearance via the kidneys (22.2 and 12.3 %ID/g at 2 h and 24 h p.i., respectively), similar to IMP288. The optical images confirmed this pattern of high TBR and renal clearance of RDC-018.

Conclusions The high tumor targeting and TBR of RDC-018 illustrate the feasibility of this pretargeted dual-modality (SPECT/fluorescence) imaging approach.