Elsevier

Radiotherapy and Oncology

Volume 98, Issue 1, January 2011, Pages 109-116
Radiotherapy and Oncology

PET in radiotherapy
Simultaneous positron emission tomography (PET) assessment of metabolism with 18F-fluoro-2-deoxy-d-glucose (FDG), proliferation with 18F-fluoro-thymidine (FLT), and hypoxia with 18fluoro-misonidazole (F-miso) before and during radiotherapy in patients with non-small-cell lung cancer (NSCLC): A pilot study

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Abstract

Objectives

To investigate the changes in tumour proliferation (using FLT), metabolism (using FDG), and hypoxia (using F-miso) during curative (chemo-) radiotherapy (RT) in patients with non-small-cell lung cancer (NSCLC).

Patients and methods

Thirty PET scans were performed in five patients (4 males, 1 female) that had histological proof of NSCLC and were candidates for curative-intent RT. Three PET-CT (Biograph S16, Siemens) scans were performed before (t0) and during (around dose 46 Gy, t46) RT with minimal intervals of 48 h between each PET-CT scan. The tracers used were 18fluoro-2deoxyglucose (FDG) for metabolism, 18fluorothymidine (FLT) for proliferation, and 18F-misonidasole (F-miso) for hypoxia. The 3 image sets obtained at each time point were co-registered (rigid: n = 9, elastic: n = 1, Leonardo, TrueD, Siemens) using FDG PET-CT as reference. VOIs were delineated (40% SUVmax values were used as a threshold) for tumours and lymph nodes on FDG PET-CT, and they were automatically pasted on FLT and F-miso PET-CT images. ANOVA and correlation analyses were used for comparison of SUVmax values.

Results

Four tumours and twelve nodes were identified on initial FDG PET-CT images. FLT SUVmax values were significantly lower (p < 0.0006) at t46 in both tumours and nodes. The decrease in FDG SUVmax values had a trend towards significance (p = 0.048). F-Miso SUVmax values were significantly higher in tumours than in nodes (p = 0.02) and did not change during radiotherapy (p = 0.39). A significant correlation was observed between FLT and FDG uptake (r = 0.56, p < 10−4) when all data were pooled together, and they remained similar when the before and during RT data were analysed separately. FDG and F-miso uptakes were significantly correlated (r = 0.59, p = 0.0004) when all data were analysed together. The best fit was obtained after adjusting for lesion type (tumour vs. node). This correlation was observed for the SUVmax measured during RT (r = 0.70, p = 0.008) but not for the pre-RT data (r = 0.19, p = 0.35). The weak correlation between FLT and F-miso uptakes only became significant (r = 0.66, p = 0.002) when the analysis was restricted to the data acquired during RT.

Conclusion

Three different PET acquisitions can be performed quasi-simultaneously (4–7 days) before and during radiotherapy in patients with NSCLC. Our results at 46 Gy suggest that a fast decrease in the proliferation of both tumours and nodes exists during radiotherapy with differences in metabolism (borderline significant decrease) and hypoxia (stable).

Section snippets

Patients

To be eligible, patients had (1) to have histological proof of invasive NSCLC, (2) to have significant FDG uptakes (i.e., higher than twice the background level) in either primary tumours or mediastinal lymphnodes at the time of inclusion, (3) to have evaluable tumour/node lesions according to RECIST criteria (Response Evaluation Criteria In Solid Tumours), (4) to be a candidate for curative-intent radiotherapy (i.e., localised non-metastatic tumours and adequate pulmonary, medical, and general

Results

Seven patients met the inclusion criteria. Patients #002 and #005 withdrew consent at the beginning of the study. Finally, 30 PET scans were performed in five patients who were fully evaluable (four males, one female) and had 4 tumours and 12 mediastinal/hilar nodes that were identified on initial FDG-PET/CT scans (Table 1). A primary tumour could not be demonstrated in patient #007 (no visible image on a contrast-enhanced CT scan and PET/CT scan, negative endoscopy with multiple biopsies, and

Discussion

The present study is the first report evaluating simultaneous investigations of three PET tracers in patients undergoing curative-intent chemo-radiotherapy for non-small-cell lung cancer. Based on SUVmax measurements made on four primary tumours and 12 lymphnodes in 30 PET-CT scans from five patients, we demonstrated significant decreases in FLT and (to a lesser extent) FDG uptakes during radiotherapy, while F-miso activity remained low and stable. The example of one patient is presented in

Conclusion

The feasibility of multi-tracer PET/CT scans performed in a short period of time prior to and during radiotherapy, as demonstrated in the present study, opens the way to a more sophisticated individualisation of NSCLC treatment. Further studies using larger sample sizes and assessing the patient outcomes are necessary.

Funding

IBA-CisBio and Cancéropole Nord-Ouest, France.

Acknowledgements

We would like to thank the patients who participated in the present study. The authors also thank the technologists of the Department of Nuclear Medicine of Rouen for their help in managing the patients for this study. We particularly thank Mr. Pierrick Gouel, Arthur Dumouchel, and Marc Thillays for their excellent collaboration. We very much appreciated the reviewers’ criticisms that contributed to significant improvements in the manuscript.

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