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

  • Pat Zanzonico
  • Guenther Koehne
  • Humilidad F. Gallardo
  • Mikhail Doubrovin
  • Ekaterina Doubrovina
  • Ronald Finn
  • Ronald G. Blasberg
  • Isabelle Riviere
  • Richard J. O’Reilly
  • Michel Sadelain
  • Steven M. Larson
Original article



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.


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.


Molecular imaging Radiobiology/dosimetry Radiopharmaceuticals Cell labeling Cell trafficking 


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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Pat Zanzonico
    • 1
  • Guenther Koehne
    • 2
    • 3
  • Humilidad F. Gallardo
    • 4
  • Mikhail Doubrovin
    • 5
    • 6
  • Ekaterina Doubrovina
    • 2
    • 3
  • Ronald Finn
    • 7
  • Ronald G. Blasberg
    • 5
    • 6
  • Isabelle Riviere
    • 3
    • 4
  • Richard J. O’Reilly
    • 2
    • 3
  • Michel Sadelain
    • 3
    • 4
  • Steven M. Larson
    • 5
  1. 1.Department of Medical PhysicsMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  2. 2.Allogeneic Transplantation ServiceMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  3. 3.Immunology ProgramMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  4. 4.Gene Transfer and Somatic Cell Engineering FacilityMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  5. 5.Department of RadiologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  6. 6.Department of NeurologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  7. 7.Radiochemistry and Cyclotron Core FacilityMemorial Sloan-Kettering Cancer CenterNew YorkUSA

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