Quantitative PET reporter gene imaging of CD8+ T cells specific for a melanoma-expressed self-antigen

Int Immunol. 2009 Feb;21(2):155-65. doi: 10.1093/intimm/dxn133. Epub 2008 Dec 23.


Adoptive transfer (AT) T-cell therapy provides significant clinical benefits in patients with advanced melanoma. However, approaches to non-invasively visualize the persistence of transferred T cells are lacking. We examined whether positron emission tomography (PET) can monitor the distribution of self-antigen-specific T cells engineered to express an herpes simplex virus 1 thymidine kinase (sr39tk) PET reporter gene. Micro-PET imaging using the sr39tk-specific substrate 9-[4-[(18)F]fluoro-3-(hydroxymethyl)-butyl]guanine ([(18)F]FHBG) enabled the detection of transplanted T cells in secondary lymphoid organs of recipient mice over a 3-week period. Tumor responses could be predicted as early as 3 days following AT when a >25-fold increase of micro-PET signal in the spleen and 2-fold increase in lymph nodes (LNs) were observed in mice receiving combined immunotherapy versus control mice. The lower limit of detection was approximately 7 x 10(5) T cells in the spleen and 1 x 10(4) T cells in LNs. Quantification of transplanted T cells in the tumor was hampered by the sr39tk-independent trapping of [(18)F]FHBG within the tumor architecture. These data support the feasibility of using PET to visualize the expansion, homing and persistence of transferred T cells. PET may have significant clinical utility by providing the means to quantify anti-tumor T cells throughout the body and provide early correlates for treatment efficacy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Female
  • Gene Transfer Techniques
  • Genes, Reporter / genetics*
  • Genes, Reporter / immunology
  • Immunodominant Epitopes / genetics
  • Immunodominant Epitopes / immunology
  • Immunodominant Epitopes / metabolism*
  • Immunotherapy, Adoptive
  • Melanoma, Experimental / immunology*
  • Melanoma, Experimental / pathology
  • Melanoma, Experimental / therapy
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Monitoring, Immunologic / trends
  • Positron-Emission Tomography / methods*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism*
  • T-Cell Antigen Receptor Specificity / genetics
  • T-Lymphocytes / diagnostic imaging
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • gp100 Melanoma Antigen


  • Immunodominant Epitopes
  • Membrane Glycoproteins
  • Pmel protein, mouse
  • Receptors, Antigen, T-Cell, alpha-beta
  • gp100 Melanoma Antigen