18F-AraG PET for CD8 Profiling of Tumors and Assessment of Immunomodulation by Chemotherapy
| Autor: | Lyna Huynh, Brailee Schulte, Juliet A Packiasamy, Tina Lam, Tony Huynh, Jelena Levi, Samuel R. Goth |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Chemotherapy Cyclophosphamide medicine.diagnostic_test business.industry medicine.medical_treatment Immunotherapy Carboplatin Basic Science Investigation Oxaliplatin 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Immune system chemistry 030220 oncology & carcinogenesis Biopsy medicine Cancer research Immunogenic cell death Radiology Nuclear Medicine and imaging business medicine.drug |
| Zdroj: | J Nucl Med |
| ISSN: | 2159-662X 0161-5505 |
| Popis: | Most clinical trials exploring various combinations of chemo- and immunotherapy rely on serial biopsy to provide information on immune response. The aim of this study was to assess the value of (18)F-arabinosyl guanine ((18)F-AraG) as a noninvasive tool that profiles tumors on the basis of the key player in adaptive antitumor response, CD8+ cells, and evaluates the immunomodulatory effects of chemotherapy. Methods: To evaluate the ability of (18)F-AraG to report on the presence of CD8+ cells within the tumor microenvironment, we imaged a panel of syngeneic tumor models (MC38, CT26, LLC, A9F1, 4T1, and B16F10) and correlated the signal intensity with the number of lymphocytes found in the tumors. The capacity of (18)F-AraG to detect immunomodulatory effects of chemotherapy was determined by longitudinal imaging of tumor-bearing mice (MC38 and A9F1) undergoing 2 types of chemotherapy: oxaliplatin/cyclophosphamide, shown to induce immunogenic cell death, and paclitaxel/carboplatin, reported to cause immunogenically silent tumor cell death. Results: In the tumor panel, (18)F-AraG revealed strikingly different uptake patterns resembling cancer-immune phenotypes observed in the clinic. A statistically significant correlation was found between the (18)F-AraG signal and the number of PD-1–positive CD8+ cells isolated from the tumors (r (2) = 0.528, P < 0.0001). In the MC38 model, paclitaxel/carboplatin did not result in an appreciable change in signal after therapy (1.69 ± 0.25 vs. 1.50 ± 0.33 percentage injected dose per gram), but oxaliplatin/cyclophosphamide treatment led to close to a 2.4-fold higher (18)F-AraG signal (1.20 ± 0.31 vs. 2.84 ± 0.93 percentage injected dose per gram). The statistically significant increase in signal after oxaliplatin/cyclophosphamide was also observed in the A9F1 model (0.95 ± 0.36 vs. 1.99 ± 0.54 percentage injected dose per gram). Conclusion: The ability of (18)F-AraG PET to assess the location and function of CD8+ cells, as well immune activity within tumors after immune priming therapy, warrants further investigation into its utility for patient selection, evaluation of optimal time to deliver immunotherapies, and assessment of combinatorial therapies. |
| Databáze: | OpenAIRE |
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