Fluorine-18-labeled fluoromisonidazole positron emission and computed tomography-guided intensity-modulated radiotherapy for head and neck cancer: a feasibility study.

PURPOSE: Hypoxia renders tumor cells radioresistant, limiting locoregional control from radiotherapy (RT). Intensity-modulated RT (IMRT) allows for targeting of the gross tumor volume (GTV) and can potentially deliver a greater dose to hypoxic subvolumes (GTV(h)) while sparing normal tissues. A Monte Carlo model has shown that boosting the GTV(h) increases the tumor control probability. This study examined the feasibility of fluorine-18-labeled fluoromisonidazole positron emission tomography/computed tomography ((18)F-FMISO PET/CT)-guided IMRT with the goal of maximally escalating the dose to radioresistant hypoxic zones in a cohort of head and neck cancer (HNC) patients. METHODS AND MATERIALS: (18)F-FMISO was administered intravenously for PET imaging. The CT simulation, fluorodeoxyglucose PET/CT, and (18)F-FMISO PET/CT scans were co-registered using the same immobilization methods. The tumor boundaries were defined by clinical examination and available imaging studies, including fluorodeoxyglucose PET/CT. Regions of elevated (18)F-FMISO uptake within the fluorodeoxyglucose PET/CT GTV were targeted for an IMRT boost. Additional targets and/or normal structures were contoured or transferred to treatment planning to generate (18)F-FMISO PET/CT-guided IMRT plans. RESULTS: The heterogeneous distribution of (18)F-FMISO within the GTV demonstrated variable levels of hypoxia within the tumor. Plans directed at performing (18)F-FMISO PET/CT-guided IMRT for 10 HNC patients achieved 84 Gy to the GTV(h) and 70 Gy to the GTV, without exceeding the normal tissue tolerance. We also attempted to deliver 105 Gy to the GTV(h) for 2 patients and were successful in 1, with normal tissue sparing. CONCLUSION: It was feasible to dose escalate the GTV(h) to 84 Gy in all 10 patients and in 1 patient to 105 Gy without exceeding the normal tissue tolerance. This information has provided important data for subsequent hypoxia-guided IMRT trials with the goal of further improving locoregional control in HNC patients.

Deep-inspiration breath-hold PET/CT: clinical findings with a new technique for detection and characterization of thoracic lesions.

UNLABELLED: Respiratory motion during PET/CT acquisition can cause misregistration and inaccuracies in calculation of standardized uptake values (SUVs). Our aim was to compare the detection and characterization of thoracic lesions on PET/CT with and without a deep-inspiration protocol. METHODS: We studied 15 patients with suspected pulmonary lesions who underwent clinical PET/CT, followed by deep-inspiration breath-hold (BH) PET/CT. In BH CT, the whole chest of the patient was scanned in 15 s at the end of deep inspiration. For BH PET, patients were asked to hold their breath 9 times for 20-s intervals. One radiologist reviewed images, aiming to detect and characterize pulmonary, nodal, and skeletal abnormalities. Clinical CT and BH CT were compared for number, size, and location of lesions. Lesion SUVs were compared between clinical PET and BH PET. Images were also visually assessed for accuracy of fusion and registration. RESULTS: All patients had lesions on clinical CT and BH CT. Pulmonary BH CT detected more lesions than clinical CT in 13 of 15 patients (86.7%). The total number of lung lesions detected increased from 53 with clinical CT to 82 with BH CT (P<0.001). Eleven patients showed a total of 31 lesions with abnormal (18)F-FDG uptake. BH PET/CT had the advantage of reducing misregistration and permitted a better localization of sites with (18)F-FDG uptake. A higher SUV was noted in 22 of 31 lesions on BH PET compared with clinical PET, with an average increase in SUV of 14%. CONCLUSION: BH PET/CT enabled an increased detection and better characterization of thoracic lesions compared with a standard PET/CT protocol, in addition to more precise localization and quantification of the findings. The technique is easy to implement in clinical practice and requires only a minor increase in the examination time.

The CT motion quantitation of lung lesions and its impact on PET-measured SUVs.

UNLABELLED: We previously reported that respiratory motion is a major source of error in quantitation of lesion activity using combined PET/CT units. CT acquisition of the lesion occurs in seconds, rather than the 4-6 min required for PET emission scans. Therefore, an incongruent lesion position during CT acquisition will bias activity estimates using PET. In this study, we systematically analyzed the range of activity concentration changes, hence SUV, for lung lesions. METHODS: Five lung cancer patients were scanned with PET/CT. In CT, data were acquired in correlation with the real-time positioning. CT images were acquired, in cine mode, at 0.45-s intervals for slightly longer (1 s) than a full respiratory cycle at each couch position. Other scanning parameters were a 0.5-s gantry rotation, 140 kVp, 175 mA, 10-mm couch increments, and a 2.5-mm slice thickness. PET data were acquired after intravenous injection of about 444-555 MBq of (18)F-FDG with a 1-h uptake period. The scanning time was 3 min per bed position for PET. Regularity in breathing was assisted by audio coaching. A commercial software program was then used to sort the acquired CT images into 10 phases, with 0% corresponding to end of inspiration (EI) and 50% corresponding to end of expiration (EE). Using the respiration-correlated CT data, images were rebinned to match the PET slice locations and thickness. RESULTS: We analyzed 8 lesions from 5 patients. Reconstructed PET emission data showed up to a 24% variation in the lesion maximum standardized uptake values (SUVs) between EI and EE phases. Examination of all the phases showed an SUV variation of up to 30%. Also, in some cases the lesion showed up to a 9-mm shift in location and up to a 21% reduction in size when measured from PET during the EI phase, compared with during the EE phase. CONCLUSION: Using respiration-correlated CT for attenuation correction, we were able to quantitate the fluctuations in PET SUVs. Because those changes may lead to estimates of lower SUVs, the respiratory phase during CT transmission scanning needs to be measured or lung motion has to be regulated for imaging lung cancer in routine clinical practice.

Reduction of respiratory motion artifacts in PET imaging of lung cancer by respiratory correlated dynamic PET: methodology and comparison with respiratory gated PET.

UNLABELLED: This study proposes a new method to reduce respiratory motion artifacts in PET images of lung cancer. The method is referred to as respiratory-correlated dynamic PET (RCDPET). RCDPET enables the acquisition of 4-dimensional PET data without the need for a respiratory tracking device. In this article, we compare this method with respiratory-gated PET (RGPET). Both methods provide the ability to correct for motion artifacts and more accurately quantitate radiotracer uptake within lung lesions. Both methods were evaluated in phantom studies and 1 patient. METHODS: With RCDPET, data are acquired in consecutive 1-s time frames. A point source attached to a rigid foam block is set on the patient's abdomen and is extended into the camera field of view at the level of the lesion by means of a low-density rod. The position of this source is used to track respiratory motion through the consecutive dynamic frames. Image frames corresponding to a user-selected lesion position within the breathing cycle, in correlation with the point source position, are then identified after scanning. The sinograms of the selected image frames are summed and then reconstructed using iterative reconstruction with segmented attenuation correction. RESULTS: The results from phantom studies with both RGPET and RCDPET were within 10% agreement, for both activity quantitation and image noise levels. In a clinical application, the quantitation of the SUV(max) and the lesion's size showed a 6% and 2% difference, respectively, between RCDPET and RGPET measurements. CONCLUSION: RCDPET can be considered as a comparable, or alternative, method to RGPET in reducing the smearing effects due to respiration and improving quantitation of PET in the thorax. One advantage of RCDPET over RGPET is the ability to retrospectively reconstruct the PET data at any phase or amplitude in the breathing cycle.

Effect of respiratory gating on quantifying PET images of lung cancer.

UNLABELLED: We have developed a new technique to gate lung 18F-FDG PET images in synchronization with the respiratory motion to reduce smearing due to breathing and improve quantitation of 18F-FDG uptake in lung lesions. METHODS: A camera-based respiratory gating system, the real-time position management (RPM), is used to monitor the respiratory cycle. The RPM provides a trigger to the PET scanner to initiate the gating cycle. Each respiratory cycle is divided into discrete bins triggered at a defined amplitude or phase within the patient's breathing motion, into which PET data are acquired. The acquired data within the time bins correspond to different lesion positions within the breathing cycle. The study includes 5 patients with lung cancer. RESULTS: Measurements of the lesions' volumes in the gated mode showed a reduction of up to 34% compared with that of the nongated measurement. This reduction in the lesion volume has been accompanied by an increase in the intensity in the 18F-FDG signal per voxel. This finding has resulted in an improvement in measurement of the maximum standardized uptake value (SUV(max)), which increased in 1 patient by as much as 159%. The total lesion glycolysis, defined as the product of the SUV(max) and the lesion volume, was also measured in gated and nongated modes and showed a consistency between the 2 measurements. CONCLUSION: We have shown that image smearing can be reduced by gating 18F-FDG PET images in synchronization with the respiratory motion. This technique allows a more accurate definition of the lesion volume and improves the quantitation specific activity of the tracer (in this case, 18F-FDG), which are distorted because of the breathing motion.

Radiotherapy treatment planning for patients with non-small cell lung cancer using positron emission tomography (PET).

PURPOSE: Many patients with non-small cell lung cancer (NSCLC) receive external beam radiation therapy as part of their treatment. Three-dimensional conformal radiation therapy (3DCRT) commonly uses computed tomography (CT) to accurately delineate the target lesion and normal tissues. Clinical studies, however, indicate that positron emission tomography (PET) has higher sensitivity than CT in detecting and staging of mediastinal metastases. Imaging with fluoro-2-deoxyglucose (FDG) PET in conjunction with CT, therefore, can improve the accuracy of lesion definition. In this pilot study, we investigated the potential benefits of incorporating PET data into the conventional treatment planning of NSCLC. Case-by-case, we prospectively analyzed planning target volume (PTV) and lung toxicity changes for a cohort of patients. MATERIALS AND METHODS: We have included 11 patients in this study. They were immobilized in the treatment position and CT simulation was performed. Following CT simulation, PET scanning was performed in the treatment position using the same body cast that was produced for CT simulation and treatment. The PTV, along with the gross target volume (GTV) and normal organs, was first delineated using the CT data set. The CT and PET transmission images were then registered in the treatment planning system using either manual or automated methods, leading to consequent registration of the CT and emission images. The PTV was then modified using the registered PET emission images. The modified PTV is seen simultaneously on both CT and PET images, allowing the physician to define the PTV utilizing the information from both data sets. Dose-volume histograms (DVHs) for lesion and normal organs were generated using both CT-based and PET+CT-based treatment plans. RESULTS: For all patients, there was a change in PTV outline based on CT images versus CT/PET fused images. In seven out of 11 cases, we found an increase in PTV volume (average increase of 19%) to incorporate distant nodal disease. Among these patients, the highest normal-tissue complication probability (NTCP) for lung was 22% with combined PET/CT plan and 21% with CT-only plan. In other four patients PTV was decreased an average of 18%. The reduction of PTV in two of these patients was due to excluding atelectasis and trimming the target volume to avoid delivering higher radiation doses to nearby spinal cord or heart. CONCLUSIONS: The incorporation of PET data improves definition of the primary lesion by including positive lymph nodes into the PTV. Thus, the PET data reduces the likelihood of geographic misses and hopefully improves the chance of achieving local control.