Olivia Squire

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

Abstract 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.

Effect of respiratory gating on reducing lung motion artifacts in PET imaging of lung cancer

Positron emission tomography (PET) has shown an increase in both sensitivity and specificity over computed tomography (CT) in lung cancer. However, motion artifacts in the 18F fluorodioxydoglucose (FDG) PET images caused by respiration persists to be an important factor in degrading PET image quality and quantification. Motion artifacts lead to two major effects: First, it affects the accuracy of quantitation, producing a reduction of the measured standard uptake value (SUV). Second, the apparent lesion volume is overestimated. Both impact upon the usage of PET images for radiation treatment planning. The first affects the visibility, or contrast, of the lesion. The second results in an increase in the planning target volume, and consequently a greater radiation dose to the normal tissues. One way to compensate for this effect is by applying a multiple-frame capture technique. The PET data are then acquired in synchronization with the respiratory motion. Reduction in smearing due to gating was investigated in both phantoms and patient studies. Phantom studies showed a dependence of the reduction in smearing on the lesion size, the motion amplitude, and the number of bins used for data acquisition. These studies also showed an improvement in the target-to-background ratio, and a more accurate measurement of the SUV. When applied to one patient, respiratory gating showed a 28% reduction in the total lesion volume, and a 56.5% increase in the SUV. This study was conducted as a proof of principle that a gating technique can effectively reduce motion artifacts in PET image acquisition.

Quantitation of respiratory motion during 4D-PET/CT acquisition

We report on the variability of the respiratory motion during 4D-PET/CT acquisition. The respiratory motion for five lung cancer patients was monitored by tracking external markers placed on the abdomen. CT data were acquired over an entire respiratory cycle at each couch position. The x-ray tube status was recorded by the tracking system, for retrospective sorting of the CT data as a function of respiration phase. Each respiratory cycle was sampled in ten equal bins. 4D-PET data were acquired in gated mode, where each breathing cycle was divided into ten 500 ms bins. For both CT and PET acquisition, patients received audio prompting to regularize breathing. The 4D-CT and 4D-PET data were then correlated according to their respiratory phases. The respiratory periods, and average amplitude within each phase bin, acquired in both modality sessions were then analyzed. The average respiratory motion period during 4D-CT was within 18% from that in the 4D-PET sessions. This would reflect up to 1.8% fluctuation in the duration of each 4D-CT bin. This small uncertainty enabled good correlation between CT and PET data, on a phase-to-phase basis. Comparison of the average-amplitude within the respiration trace, between 4D-CT and 4D- PET, on a bin-by-bin basis show a maximum deviation of approximately 15%. This study has proved the feasibility of performing 4D-PET/CT acquisition. Respiratory motion was in most cases consistent between PET and CT sessions, thereby improving both the attenuation correction of PET images, and co-registration of PET and CT images. On the other hand, in two patients, there was an increased partial irregularity in their breathing motion, which would prevent accurately correlating the corresponding PET and CT images.

Deep-Inspiration Breath-Hold PET/CT: Clinical Findings with a New Technique for Detection and Characterization of Thoracic Lesions

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 18F-FDG uptake. BH PET/CT had the advantage of reducing misregistration and permitted a better localization of sites with 18F-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.

Pharmacokinetic Assessment of the Uptake of 16β-18F-Fluoro-5α-Dihydrotestosterone (FDHT) in Prostate Tumors as Measured by PET

The aim of this study was to develop a clinically applicable noninvasive method to quantify changes in androgen receptor (AR) levels based on 18F-16β-fluoro-5α-dihydrotestosterone (18F-FDHT) PET in prostate cancer patients undergoing therapy. Methods: Thirteen patients underwent dynamic 18F-FDHT PET over a selected tumor. Concurrent venous blood samples were acquired for blood metabolite analysis. A second cohort of 25 patients injected with 18F-FDHT underwent dynamic PET of the heart. These data were used to generate a population-based input function, essential for pharmacokinetic modeling. Linear compartmental pharmacokinetic models of increasing complexity were tested on the tumor tissue data. Four suitable models were applied and compared using the Bayesian information criterion (BIC). Model 1 consisted of an instantaneously equilibrating space, followed by a unidirectional trap. Models 2a and 2b contained a reversible space between the instantaneously equilibrating space and the trap, into which metabolites were excluded (2a) or allowed (2b). Model 3 built on model 2b with the addition of a second reversible space preceding the unidirectional trap and from which metabolites were excluded. Results: The half-life of the 18F-FDHT in blood was between 6 and 7 min. As a consequence, the uptake of 18F-FDHT in prostate cancer lesions reached a plateau within 20 min as the blood-borne activity was consumed. Radiolabeled metabolites were shown not to bind to ARs in in vitro studies with CWR22 cells. Model 1 produced reasonable and robust fits for all datasets and was judged best by the BIC for 16 of 26 tumor scans. Models 2a, 2b, and 3 were judged best in 7, 2, and 1 cases, respectively. Conclusion: Our study explores the clinical potential of using 18F-FDHT PET to estimate free AR concentration. This process involved the estimation of a net uptake parameter such as the ktrap of model 1 that could serve as a surrogate measure of AR expression in metastatic prostate cancer. Our initial studies suggest that a simple body mass–normalized standardized uptake value correlates reasonably well to model-based ktrap estimates, which we surmise may be proportional to AR expression. Validation studies to test this hypothesis are underway.

Differential metabolism and pharmacokinetics of L-[1-11C]-methionine and 2-[18F] fluoro-2-deoxy-D-glucose (FDG) in androgen independent prostate cancer

Metabolic imaging with positron emission tomography (PET) for the staging and monitoring of treatment response has important implications in clinical oncology. The choice of radiotracer is likely to be critically important. The objective of our study was to compare the pharmacokinetics of C-11-methionine with FDG in a group of androgen independent patients with metastatic prostate cancer, to determine the differential metabolism of the two tracers, and to determine the optimal time of imaging after injection in treated and untreated patients. A total of 29 dynamic scans (19 pretreatment and 10 posttreatment) were performed in 10 patients with progressive or new lesions on bone scans (index lesions). A total of 13 index lesions were identified in baseline scans. Patients were infused with 370 MBq C-11-methionine on the couch and 32 dynamic images acquired over 60 minutes. After at least 5 half-lives of C-11, patients were then dynamically imaged (15 frames) for 45 minutes with FDG. Index lesions demonstrated both C-11-methionine (13/13) and FDG uptake (12/13). The plateau of methionine uptake in tumor was reached by 10 minutes, and thereafter remained constant. FDG tumor uptake was slower and for some patients continued to rise beyond 45 minutes. The clearance of blood activity for C-11-methionine was more rapid than FDG and the plateau was 10 and 45 minutes respectively. In 5 patients scanned after therapy, 4 responded to treatment, which was reflected by a corresponding decrease in C-11-methionine and FDG tumor uptake. No change was observed in the relative shape of the uptake curves however, between the C-11-methionine and the FDG uptake, either in the 4 who responded to treatment or for one patient who did not respond. The SUV of C-11-methionine was significantly higher than for FDG (P <.008). Both C-11-methionine and FDG are taken up in index lesions in patients with progressive prostate cancer. The advantages of C-11-methionine over FDG are the higher tumor to blood ratio, the more rapid tumor uptake allowing earlier imaging, and a flatter plateau rendering lesion activity on whole body images more uniform and less susceptible to gradual change than FDG. This indicates the feasibility of whole body PET imaging with decay corrected C-11-methionine. Additional studies are planned to define optimal imaging times after different therapies in comparison to FDG and bone scans.

Changes in FDG Tumor Uptake during and after Fractionated Radiation Therapy in a Rodent Tumor Xenograft

OBJECTIVE: The uptake of FDG was measured before, during, and after fractionated radiation in order to evaluate the potential of FDG-PET imaging as an indicator of tumor response.METHODS: The study was performed with nude rats bearing the human neuroblastoma BE(2)C tumor xenografts. Tumors were irradiated with 10 fractions of 2 Gy using a 320 kV(p) X-ray unit. Following a baseline FDG-PET scan, repeat scans were performed weekly until animal sacrifice. The rodents were given up to 10 FDG-PET scans, over a period of up to 75 days posttreatment.RESULTS AND CONCLUSIONS: Neither, the average and maximum activity/cc of FDG tumor uptake, nor the respective standardized uptake values (SUV), correlated with tumor response. Instead, the total FDG uptake (defined as the product of the average FDG activity/cc with the tumor volume) correlated better with tumor response.

Excess Muscle FDG Uptake in an Euglycaemic Patient That Is Corrected by Fasting

A 61-year-old non-diabetic woman underwent a non-diagnostic FDG PET study due to ingestion of milk and sugar 150 minutes prior to injection of FDG despite being euglycaemic. A repeat study 2 days later showed 4 pathological foci of FDG uptake, of which only two could be seen retrospectively on the original study. The loss of lesion perspicuity and suppression of FDG uptake in the pathological lesions was corrected by fasting for more than 6 hours. The calculated SUV suppression due to eating could be corrected by normalizing according to the average of the patients liver SUV. Proper patient preparation is essential in any medical procedure but even more so in FDG PET imaging, as small pathological lesions may be missed if the patient is improperly prepared.