Variation in SGM-101 fluorescence is associated with tumor biology in primary colorectal cancer and colorectal liver metastases

BACKGROUND: SGM-101 is a carcinoembryonic antigen (CEA)-targeted near-infrared tracer, but fluorescence varies between and within colorectal tumors. We examined biological and tissue-contextual factors associated with ex vivo fluorescence in primary colorectal cancer (CRC) and colorectal liver metastases (CRLM). METHODS: Formalin-fixed paraffin-embedded tissue blocks from 29 patients enrolled in four prospective studies, all receiving 10 mg SGM-101 four days before the planned procedure, were evaluated for CEA expression, CD31 intensity, tumor-to-stroma ratio (TtSR), and mean fluorescence intensity (MFI). Tumor-to-background ratio (TBR) was available for 83 of 97 blocks from 27 patients. Patient-clustered mixed-effects models constituted the principal inferential analyses; unclustered block-level tests were descriptive and exploratory. Parsimonious ordinal-score models assessed sensitivity to model complexity. RESULTS: In lesion-specific mixed-effects models, CEA expression was associated with TBR in CRLM (overall p = 0.017), whereas TtSR ≥1 was associated with higher TBR in primary CRC (ratio 1.48, 95% confidence interval [CI] 1.06-2.06; p = 0.027). In the full multivariable model, only lesion type was associated with TBR: CRLM had lower TBR than primary CRC (ratio 0.74, 95% CI 0.57-0.96; p = 0.026), an estimate retained in sensitivity analysis. This comparison incorporates different organ-specific backgrounds. Neoadjuvant treatment was not associated with MFI or TBR after patient clustering, and no evaluated variable was independently associated with MFI. CONCLUSIONS: Associations with SGM-101 fluorescence were context dependent. Target expression and tissue composition may contribute to local fluorescence variation, whereas organ-specific background materially affects TBR. Associations with neoadjuvant treatment were not supported after patient clustering.