Back to 2025 Abstracts
SPECIFIC TARGETING OF PANCREATIC CANCER IN ORTHOTOPIC MOUSE MODELS WITH AN ANTI CA-19-9 ANTIBODY CONJUGATED TO A NIR FLUOROPHORE
Javier Bravo
*1, Kristin E. Cox
1, Sunidhi Jaiswal
1, Siamak Amirfakhri
1, Thinzar Lwin
3, Sumbal Talib
2, Maneesh Jain
2, Robert Hoffman
1, Aaron Mohs
2, Surinder Batra
2, Michael Bouvet
11Surgery, UC San Diego, San Diego, CA; 2University of Nebraska Medical Center, Omaha, NE; 3City of Hope, Duarte, CA
Background:
Surgical resection currently offers the only possibility for a cure for pancreatic cancer, and it is difficult to achieve due to inability to accurately identify true margins. The field of fluorescence-guided surgery (FGS) with tumor-specific markers offers promising tools for improving the detection of tumors and metastatic disease, as well as aiding the surgeon in achieving complete surgical resection. In this study, we use an anti CA19-9 antibody conjugated to a near infrared (NIR) fluorophore in orthotopic mouse models to attempt to target pancreatic cancer cells.
Methods: Orthotopic models of the human pancreatic cancer cell line SW1990 were established by implanting tumor fragments into the pancreas of athymic mice. For tumor labeling, anti-CA19-9 or IgG as a control were conjugated with the NIR dye IRDye800CW. Mice received 50 µg of CA19-9-IR800 or 50 µg IgG-IR800 via tail vein injection and were imaged after 72 hours. Fluorescence imaging was performed using the LI-COR Pearl Small Animal Imaging System and the Stryker 1688 laparoscopic imaging system with SPY fluorescence. Tumor to liver ratios (TLR) and tumor to background ratios (TBR) were calculated by dividing the mean fluorescence intensity of the tumor versus the liver or surrounding tissue.
Results: The antibody-dye conjugate was analyzed on a spectrophotometer and demonstrated a dye-to-protein ratio of 1.2. Using the LI-COR Pearl imaging system in the orthotopic models of SW1990 labelled with CA19-9-IR800, the TLR was 3.15 (±0.72) compared to 0.60 (±0.10) for IgG-IR800 (Figure 1). When analyzed on SPY fluorescence, the anti-CA19-9-1R800 conjugate demonstrated a TBR of 2.34 (±0.88) and a TLR of 2.2 (±0.95), compared to 1.1 (±0.26) and 0.68 (±0.14) in the IgG-IR800 group (Figure 2). Fluorescence biodistribution studies showed that the maximal fluorescence signal for mice that received CA19-9-IR800 was in the tumors, while the mice that received IgG-IR800 had the highest signals in the liver with relatively low levels seen in the tumors. In both groups, minimal fluorescence signal was detected in the normal pancreas, spleen, stomach, cecum, kidney, lung, or skin.
Conclusions: Anti-CA19-9-IR800 provides specific in-vivo targeting of the human pancreatic cancer cell line SW1990 in orthotopic mouse models and demonstrated superior TLRs and TBRs when compared to IgG-IR800 in both NIR and SPY fluorescence imaging. This tumor-specific fluorescent antibody is a promising clinical tool for improved identification of pancreatic cancer tumors and resection margins, with the potential to be used in FGS and positively impact overall patient survival.
Figure 1: CA19-9-IR800 brightly targets orthotopic mouse models of pancreatic cancer. A) NIR and A’) bright light imaging of pancreatic tumor labeled with 50 µg CA19-9-IR800. B) NIR and B’) bright light imaging of pancreatic tumor and non-specific labeling with 50 µg IgG-IR800. C) Average tumor to liver ratio of those treated with CA19-9-800 or IgG-IR800. White arrow: tumor, yellow arrow: normal pancreas. Scale bar: 1 cm.
Figure 2. SW1990 cell-line orthotopic mouse model of pancreatic cancer labeled with 50 µg CA19-9-IR800. A) Bright light image, SPY fluorescence and overlay modes on the Stryker 1688 laparoscopic imaging device brightly identifies tumors. B) Average tumor to background ratio and tumor to liver ratio of mice treated with CA19-9-800 or IgG-IR800.
Back to 2025 Abstracts
