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Single chain antigen binding protein (sFv CC49): first human studies in colorectal carcinoma metastatic to liver
S M Larson1, A M El-Shirbiny, C R Divgi
1Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Background:
An sFv fragment of the anti-TAG-72 monoclonal antibody CC49 has been developed and has shown promise in improved targeting to colorectal carcinoma in animal studies. In this study the authors report their initial experience in human patients after intravenous injection.
Methods:
Five patients with colorectal carcinoma metastatic to the liver were studied prior to surgery. High performance liquid chromatography showed a low level of aggregation (< 10% complex formation), before and after radiolabeling with iodogen. Prior to radiolabeling, 123I was brought to the dry form, phosphate buffer added and titrated to a pH of 7, with diluted hydrochloric acid. 123I was injected in doses of 26, 12, 27, 25 and 1 millicurie, respectively, and labeled to a 5-mg fragment. Single photon emission computed tomography and whole body imaging were performed at 4-6 hours, and 24 hours, respectively, after injection.
Results:
The agent was rapidly cleared from the blood with biphasic clearance T-1/2 of 30 minutes and 10.5 hours, respectively. Distribution from whole body imaging confirmed rapid equilibration with extracellular fluid, and clearance T-1/2 from the body was comparable to the slower component of blood clearance. The spleen was visualized in all patients, and the testes were imaged in 67% of male patients. Renal excretion was noted with early uptake and clearance from the renal parenchyma except in one patient in whom renal parenchyma retention was intense. Although image quality was suboptimal, tumor was visualized in all five patients in both primary and metastatic lesions. At surgery, (16-24 hours postinjection), the tumor retained significant concentrations of the radiotracer, with metastatic tumor/normal liver ratios of approximately 1:5-3:1. No patient had any associated symptom or change in biochemical and hematopoietic status.
Conclusions:
This study showed that sFv is safe, tissue equilibration and clearance is rapid, and early, same-day imaging of the primary and metastatic tumors is feasible in patients colorectal carcinoma. Further studies are warranted to define a more optimal mass of sFv CC49 dose for tumor targeting.
Insights
This study demonstrates that the single-chain variable fragment (sFv) CC49 is safe for colorectal carcinoma patients, enabling rapid imaging of tumors. Further research is needed to optimize the sFv CC49 dose for effective tumor targeting.
Area of Science:
- Oncology
- Radiopharmaceuticals
- Immunotherapy
Background:
- Development of a single-chain variable fragment (sFv) from the anti-TAG-72 monoclonal antibody CC49.
- Promising results in animal models for targeting colorectal carcinoma.
- Initial human patient experience after intravenous administration.
Purpose of the Study:
- Evaluate the safety and efficacy of sFv CC49 in human patients with colorectal carcinoma.
- Assess the pharmacokinetic profile and biodistribution of radiolabeled sFv CC49.
- Determine the feasibility of early tumor imaging using sFv CC49.
Main Methods:
- Five patients with metastatic colorectal carcinoma underwent intravenous injection of 123I-labeled sFv CC49.
- High-performance liquid chromatography confirmed low aggregation levels.
- Single photon emission computed tomography and whole-body imaging were performed at 4-6 and 24 hours post-injection.
Main Results:
- Rapid blood clearance with biphasic T-1/2 (30 min and 10.5 hours).
- Tumor visualization in all five patients with significant radiotracer retention.
- Favorable metastatic tumor to normal liver ratios (1.5-3:1) at 16-24 hours post-injection.
- No adverse symptoms or changes in patient status observed.
Conclusions:
- sFv CC49 is safe for colorectal carcinoma patients.
- Rapid tissue equilibration and clearance allow for same-day tumor imaging.
- Further studies are required to optimize the sFv CC49 dose for enhanced tumor targeting.