European Journal of Nuclear Medicine and Molecular Imaging

, Volume 33, Issue 9, pp 988–997

[131I]FIAU labeling of genetically transduced, tumor-reactive lymphocytes: cell-level dosimetry and dose-dependent toxicity

Authors

    • Department of Medical PhysicsMemorial Sloan-Kettering Cancer Center
  • Guenther Koehne
    • Allogeneic Transplantation ServiceMemorial Sloan-Kettering Cancer Center
    • Immunology ProgramMemorial Sloan-Kettering Cancer Center
  • Humilidad F. Gallardo
    • Gene Transfer and Somatic Cell Engineering FacilityMemorial Sloan-Kettering Cancer Center
  • Mikhail Doubrovin
    • Department of RadiologyMemorial Sloan-Kettering Cancer Center
    • Department of NeurologyMemorial Sloan-Kettering Cancer Center
  • Ekaterina Doubrovina
    • Allogeneic Transplantation ServiceMemorial Sloan-Kettering Cancer Center
    • Immunology ProgramMemorial Sloan-Kettering Cancer Center
  • Ronald Finn
    • Radiochemistry and Cyclotron Core FacilityMemorial Sloan-Kettering Cancer Center
  • Ronald G. Blasberg
    • Department of RadiologyMemorial Sloan-Kettering Cancer Center
    • Department of NeurologyMemorial Sloan-Kettering Cancer Center
  • Isabelle Riviere
    • Immunology ProgramMemorial Sloan-Kettering Cancer Center
    • Gene Transfer and Somatic Cell Engineering FacilityMemorial Sloan-Kettering Cancer Center
  • Richard J. O’Reilly
    • Allogeneic Transplantation ServiceMemorial Sloan-Kettering Cancer Center
    • Immunology ProgramMemorial Sloan-Kettering Cancer Center
  • Michel Sadelain
    • Immunology ProgramMemorial Sloan-Kettering Cancer Center
    • Gene Transfer and Somatic Cell Engineering FacilityMemorial Sloan-Kettering Cancer Center
  • Steven M. Larson
    • Department of RadiologyMemorial Sloan-Kettering Cancer Center
Original article

DOI: 10.1007/s00259-005-0057-3

Cite this article as:
Zanzonico, P., Koehne, G., Gallardo, H.F. et al. Eur J Nucl Med Mol Imaging (2006) 33: 988. doi:10.1007/s00259-005-0057-3

Abstract

Purpose

Donor T cells have been shown to be reactive against and effective in adoptive immunotherapy of Epstein-Barr virus (EBV) lymphomas which develop in some leukemia patients post marrow transplantation. These T cells may be genetically modified by incorporation of a replication-incompetent viral vector (NIT) encoding both an inactive mutant nerve growth factor receptor (LNGFR), as an immunoselectable surface marker, and a herpes simplex virus thymidine kinase (HSV-TK), rendering the cells sensitive to ganciclovir. The current studies are based on the selective HSV-TK-catalyzed trapping (phosphorylation) of the thymidine analog [131I]-2′-fluoro-2′-deoxy-1-β-D-arabinofuransyl-5-iodo-uracil (FIAU) as a means of stably labeling such T cells for in vivo trafficking (including tumor targeting) studies. Because of the radiosensitivity of lymphocytes and the potentially high absorbed dose to the nucleus from intracellular 131I (even at tracer levels), the nucleus absorbed dose (Dn) and dose-dependent immune functionality were evaluated for NIT+ T cells labeled ex vivo in [131I]FIAU-containing medium.

Methods

Based on in vitro kinetic studies of [131I]FIAU uptake by NIT+ T cells, Dn was calculated using an adaptation of the MIRD formalism and the recently published MIRD cellular S factors. Immune cytotoxicity of [131I]FIAU-labeled cells was assayed against 51Cr-labeled target cells [B-lymphoblastoid cells (BLCLs)] in a standard 4-h release assay.

Results and conclusion

At median nuclear absorbed doses up to 830 cGy, a 51Cr-release assay against BLCLs showed no loss of immune cytotoxicity, thus demonstrating the functional integrity of genetically transduced, tumor-reactive T cells labeled at this dose level for in vivo cell trafficking and tumor targeting studies.

Keywords

Molecular imagingRadiobiology/dosimetryRadiopharmaceuticalsCell labelingCell trafficking

Copyright information

© Springer-Verlag 2006