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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