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Localization by hand-held gamma probe of tumor labeled with antibody "cocktail"
A Sardi1, M A Siddiqi, G Hinkle
1Division of Surgical Oncology, Ohio State University Hospital, College of Medicine, Columbus 43210.
Abstract:
Five groups (n = 4) of congenitally athymic female nude mice bearing subcutaneous implants of CX-1 and/or SW-1116 tumor in the hind limbs received iodine-125 radio-labeled monoclonal antibodies (MoAbs) B72.3 (two groups), 17-1A (two groups), and cocktail (one group) (iodogen method, 50 microCi/10 micrograms/mouse). Daily probe counts were made in duplicate with a hand-held detector over each tumor site and the front leg (background) for 21 days. Animals were sacrificed and appropriate well counts were obtained. All the single MoAb preparations localized well in both tumor cell lines. Uptake of monoclonal antibody 17-1A was similar in the two tumor cell lines, with counts initially high and slowly decreasing over the 21-day period. Tumor/background ratios continued to increase over time, indicating that both tumor lines have similar antigenic expression for the monoclonal antibody 17-1A. This was not the case for monoclonal antibody B72.3, which showed a preferential uptake by the CX-1 tumor, with higher initial counts and prolonged binding of the antibody, giving rise to higher tumor/background ratios. The mixture of monoclonal antibodies B72.3 and 17-1A markedly improved the uptake by the CX-1 tumor cell line but not that by the SW-1116 cell line, where the effect was negative when compared to the uptake of the single MoAb preparations. The use of a monoclonal antibody mixture can enhance targeting of some tumor sites. Due to the heterogeneity of tumor cell lines, even within the same animal, different mixtures of monoclonal antibodies are needed to increase the targeting of tumor.
Insights
Radio-labeled monoclonal antibodies (MoAbs) show varied tumor targeting. Antibody 17-1A targets both cell lines similarly, while B72.3 preferentially targets CX-1 tumors. Mixtures can enhance targeting, but tumor heterogeneity necessitates tailored antibody combinations.
Area of Science:
- Immunology
- Oncology
- Radiopharmaceuticals
Background:
- Monoclonal antibodies (MoAbs) are increasingly used in cancer diagnostics and therapeutics.
- Targeting specific tumor antigens with radiolabeled MoAbs can improve diagnostic accuracy and therapeutic efficacy.
- Understanding MoAb uptake and retention in different tumor types is crucial for optimizing their use.
Purpose of the Study:
- To evaluate the in vivo targeting and localization of iodine-125 radio-labeled monoclonal antibodies (MoAbs) B72.3 and 17-1A in distinct human tumor xenografts (CX-1 and SW-1116) in nude mice.
- To assess the efficacy of a cocktail of MoAbs B72.3 and 17-1A in enhancing tumor targeting compared to individual MoAbs.
- To investigate the impact of tumor cell line heterogeneity on MoAb uptake and retention.
Main Methods:
- Congenitally athymic nude mice bearing subcutaneous CX-1 and/or SW-1116 tumor xenografts were administered iodine-125 labeled MoAbs (B72.3, 17-1A, or a cocktail) via the iodogen method.
- In vivo gamma probe counts were performed daily over tumor sites and background regions for 21 days.
- Ex vivo well counts of harvested tumors and organs were obtained post-sacrifice to determine biodistribution and tumor-to-background ratios.
Main Results:
- Both individual MoAbs, B72.3 and 17-1A, demonstrated good localization in both CX-1 and SW-1116 tumor xenografts.
- MoAb 17-1A showed similar uptake and retention in both tumor lines, with increasing tumor/background ratios over time, indicating comparable antigenic expression.
- MoAb B72.3 exhibited preferential uptake and prolonged binding in the CX-1 tumor line, resulting in higher tumor/background ratios compared to SW-1116.
- The MoAb cocktail significantly enhanced uptake in CX-1 tumors but showed a negative effect in SW-1116 tumors compared to single MoAb administration.
- These findings highlight differential targeting capabilities and the influence of tumor heterogeneity on MoAb cocktail efficacy.
Conclusions:
- Individual monoclonal antibodies (MoAbs) possess distinct targeting specificities for different tumor xenografts.
- A mixture of MoAbs can enhance tumor targeting in certain cases, but its effectiveness is dependent on the specific tumor types and their antigenic profiles.
- Tumor heterogeneity necessitates the development of customized MoAb cocktails to achieve optimal tumor targeting and potentially improve therapeutic outcomes.