Single chain antigen binding protein (sFv CC49): First human studies in colorectal carcinoma metastatic to liver

Steven M. Larson, Ayda M. El-Shirbiny, Chaitanya R. Divgi, George Sgouros, Ronald D. Finn, Jorg Tschmelitsch, Antonio Picon, Marc Whitlow, Jeffrey Schlom, Jiaju Zhang, Alfred M. Cohen

Research output: Contribution to journalArticle

Abstract

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- 1/4 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 spy 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.

Original languageEnglish (US)
Pages (from-to)2458-2468
Number of pages11
JournalCancer
Volume80
Issue number12 SUPPL.
StatePublished - Dec 15 1997

Keywords

  • Colorectal carcinoma
  • Intravenous injection
  • Liver
  • Metastatic
  • SFv CC49

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Single chain antigen binding protein (sFv CC49): First human studies in colorectal carcinoma metastatic to liver'. Together they form a unique fingerprint.

  • Cite this

    Larson, S. M., El-Shirbiny, A. M., Divgi, C. R., Sgouros, G., Finn, R. D., Tschmelitsch, J., Picon, A., Whitlow, M., Schlom, J., Zhang, J., & Cohen, A. M. (1997). Single chain antigen binding protein (sFv CC49): First human studies in colorectal carcinoma metastatic to liver. Cancer, 80(12 SUPPL.), 2458-2468.