Using Radiolabeled 3′-Deoxy-3′-18F-Fluorothymidine with PET to Monitor the Effect of Dexamethasone on Non–Small Cell Lung Cancer
| Autor: | Jawana M. Lawhorn-Crews, Shirish M. Gadgeel, Christopher I. McHugh, Thomas J. Mangner, Anthony F. Shields, Monica Thipparthi, Jing Li, Janice Akoury, Lisa Polin, Kirk A. Douglas, Manohar Ratnam |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Chemotherapy medicine.diagnostic_test business.industry medicine.medical_treatment medicine.disease 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Glucocorticoid receptor Pemetrexed Positron emission tomography 030220 oncology & carcinogenesis Toxicity medicine Cancer research Radiology Nuclear Medicine and imaging Cytotoxicity business Lung cancer Dexamethasone medicine.drug |
| Zdroj: | Journal of Nuclear Medicine. 59:1544-1550 |
| ISSN: | 2159-662X 0161-5505 |
| Popis: | Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality in the United States, and pemetrexed-based therapies are regularly used to treat nonsquamous NSCLC. Despite widespread use, pemetrexed has a modest effect on progression-free survival, with varying efficacy between individuals. Recent work has indicated that dexamethasone, given to prevent pemetrexed toxicity, is able to protect a subset of NSCLC cells from pemetrexed cytotoxicity by temporarily suppressing the S phase of the cell cycle. Therefore, dexamethasone might block treatment efficacy in a subpopulation of patients and might be contributing to the variable response to pemetrexed. Methods: Differences in retention of the experimental PET tracer 3'-deoxy-3'-fluorothymidine (FLT) were used to monitor S-phase suppression by dexamethasone in NSCLC cell models, animals with tumor xenografts, and patients with advanced cancer. Results: Significant reductions in tracer uptake were observed after 24 h of dexamethasone treatment in NSCLC cell lines and xenograft models expressing high levels of glucocorticoid receptor α, coincident with pemetrexed resistance visualized by attenuation of the flare effect associated with pemetrexed activity. Two of 4 patients imaged in a pilot study with 18F-FLT PET after dexamethasone treatment demonstrated reductions in tracer uptake from baseline, with a variable response between individual tumor lesions. Conclusion: 18F-FLT PET represents a useful method for the noninvasive monitoring of dexamethasone-mediated S-phase suppression in NSCLC and might provide a way to individualize chemotherapy in patients receiving pemetrexed-based regimens. |
| Databáze: | OpenAIRE |
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