Monitoring the efficacy of adoptively transferred prostate cancer-targeted human T lymphocytes with PET and bioluminescence imaging Journal Article


Authors: Dobrenkov, K.; Olszewska, M.; Likar, Y.; Shenker, L.; Gunset, G.; Cai, S.; Pillarsetty, N.; Hricak, H.; Sadelain, M.; Ponomarev, V.
Article Title: Monitoring the efficacy of adoptively transferred prostate cancer-targeted human T lymphocytes with PET and bioluminescence imaging
Abstract: Noninvasive imaging technologies have the potential to enhance the monitoring and improvement of adoptive therapy with tumor-targeted T lymphocytes. We established an imaging methodology for the assessment of spatial and temporal distributions of adoptively transferred genetically modified human T cells in vivo for treatment monitoring and prediction of tumor response in a systemic prostate cancer model. Methods: RM1 murine prostate carcinoma tumors transduced with human prostate-specific membrane antigen (hPSMA) and a Renilla luciferase reporter gene were established in SCID/beige mice. Human T lymphocytes were transduced with chimeric antigen receptors (CAR) specific for either hPSMA or human carcinoembryonic antigen (hCEA) and with a fusion reporter gene for herpes simplex virus type 1 thymidine kinase (HSV1tk) and green fluorescent protein, with or without click beetle red luciferase. The localization of adoptively transferred T cells in tumor-bearing mice was monitored with 2′-18F-fluoro-2′-deoxy-1-β-D- arabinofuranosyl-5-ethyluracil (18F-FEAU) small-animal PET and bioluminescence imaging (BLI). Results: Cotransduction of CAR-expressing T cells with the reporter gene did not affect CAR-mediated cytotoxicity. BLI of Renilla and click beetle red luciferase expression enabled concurrent imaging of adoptively transferred T cells and systemic tumors in the same animal. hPSMA-specific T lymphocytes persisted longer than control hCEA-targeted T cells in lung hPSMA-positive tumors, as indicated by both PET and BLI. Precise quantification of T-cell distributions at tumor sites by PET revealed that delayed tumor progression was positively correlated with the levels of 18F-FEAU accumulation in tumor foci in treated animals. Conclusion: Quantitative noninvasive monitoring of genetically engineered human T lymphocytes by PET provides spatial and temporal information on T-cell trafficking and persistence. PET may be useful for predicting tumor response and for guiding adoptive T-cell therapy. Copyright © 2008 by the Society of Nuclear Medicine, Inc.
Keywords: controlled study; human cell; nonhuman; positron emission tomography; radiopharmaceuticals; t lymphocyte; t-lymphocytes; mouse; animals; mice; carcinoembryonic antigen; green fluorescent protein; cell line; mice, scid; molecular imaging; prostate cancer; prostatic neoplasms; imaging system; prostate specific membrane antigen; genetic transfection; positron-emission tomography; fusion gene; arabinofuranosyluracil; green fluorescent proteins; cytotoxicity, immunologic; thymidine kinase; genes, reporter; herpesvirus 1, human; fluorine 18; pet; bioluminescence; adoptive immunotherapy; immunotherapy, adoptive; glutamate carboxypeptidase ii; antigens, surface; viral proteins; renilla luciferin 2 monooxygenase; 5 ethyl 2' fluorouracil arabinoside f 18; 18f-feau; hsv1tk; tomography scanners, x-ray computed
Journal Title: Journal of Nuclear Medicine
Volume: 49
Issue: 7
ISSN: 0161-5505
Publisher: Society of Nuclear Medicine  
Date Published: 2008-07-01
Start Page: 1162
End Page: 1170
Language: English
DOI: 10.2967/jnumed.107.047324
PUBMED: 18552144
PROVIDER: scopus
PMCID: PMC2756034
DOI/URL:
Notes: --- - "Cited By (since 1996): 16" - "Export Date: 17 November 2011" - "CODEN: JNMEA" - "Source: Scopus"
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MSK Authors
  1. Vladimir Ponomarev
    114 Ponomarev
  2. Larissa Shenker
    18 Shenker
  3. Yury N Likar
    7 Likar
  4. Shangde Cai
    42 Cai
  5. Hedvig Hricak
    397 Hricak
  6. Michel W J Sadelain
    531 Sadelain
  7. Gertrude Mary Gunset
    16 Gunset