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.

Four-dimensional (4D) PET/CT imaging of the thorax.

We have reported in our previous studies on the methodology, and feasibility of 4D-PET (Gated PET) acquisition, to reduce respiratory motion artifact in PET imaging of the thorax. In this study, we expand our investigation to address the problem of respiration motion in PET/CT imaging. The respiratory motion of four lung cancer patients were monitored by tracking external markers placed on the thorax. A 4D-CT acquisition was performed using a "step-and-shoot" technique, in which computed tomography (CT) projection data were acquired over a complete respiratory cycle at each couch position. The period of each CT acquisition segment was time stamped with an "x-ray ON" signal, which was recorded by the tracking system. 4D-CT data were then sorted into 10 groups, according to their corresponding phase of the breathing cycle. 4D-PET data were acquired in the gated mode, where each breathing cycle was divided into ten 0.5 s bins. For both CT and PET acquisitions, patients received audio prompting to regularize breathing. The 4D-CT and 4D-PET data were then correlated according to respiratory phase. The effect of 4D acquisition on improving the co-registration of PET and CT images, reducing motion smearing, and consequently increase the quantitation of the SUV, were investigated. Also, quantitation of the tumor motions in PET, and CT, were studied and compared. 4D-PET with matching phase 4D-CTAC showed an improved accuracy in PET-CT image co-registration of up to 41%, compared to measurements from 4D-PET with clinical-CTAC. Gating PET data in correlation with respiratory motion reduced motion-induced smearing, thereby decreasing the observed tumor volume, by as much as 43%. 4D-PET lesions volumes showed a maximum deviation of 19% between clinical CT and phase- matched 4D-CT attenuation corrected PET images. In CT, 4D acquisition resulted in increasing the tumor volume in two patients by up to 79%, and decreasing it in the other two by up to 35%. Consequently, these corrections have yielded an increase in the measured SUV by up to 16% over the clinical measured SUV, and 36% over SUV's measured in 4D-PET with clinical-CT Attenuation Correction (CTAC) SUV's. Quantitation of the maximum tumor motion amplitude, using 4D-PET and 4D-CT, showed up to 30% discrepancy between the two modalities. We have shown that 4D PET/CT is clinically a feasible method, to correct for respiratory motion artifacts in PET/CT imaging of the thorax. 4D PET/CT acquisition can reduce smearing, improve the accuracy in PET-CT co-registration, and increase the measured SUV. This should result in an improved tumor assessment for patients with lung malignancies.

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.

Standardized uptake value in pediatric patients: an investigation to determine the optimum measurement parameter.

Although the standardized uptake value (SUV) is currently used in fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging, concerns have been raised over its accuracy and clinical relevance. Dependence of the SUV on body weight has been observed in adults and this should be of concern in the pediatric population, since there are significant body changes during childhood. The aim of the present study was to compare SUV measurements based on body weight, body surface area and lean body mass in the pediatric population and to determine a more reliable parameter across all ages. Sixty-eight pediatric FDG-PET studies were evaluated. Age ranged from 2 to 17 years and weight from 11 to 77 kg. Regions of interest were drawn at the liver for physiologic comparison and at FDG-avid malignant lesions. SUV based on body weight (SUV(bw)) varied across different weights, a phenomenon less evident when body surface area (SUV(bsa)) normalization is applied. Lean body mass-based SUV (SUV(lbm)) also showed a positive correlation with weight, which again was less evident when normalized to bsa (SUV(bsa-lbm)). The measured liver SUV(bw) was 1.1+/-0.3, a much lower value than in our adult population (1.9+/-0.3). The liver SUV(bsa) was 7.3+/-1.3. The tumor sites had an SUV(bw) of 4.0+/-2.7 and an SUV(bsa) of 25.9+/-15.4 (65% of the patients had neuroblastoma). The bsa-based SUVs were more constant across the pediatric ages and were less dependent on body weight than the SUV(bw). These results indicate that SUV calculated on the basis of body surface area is a more uniform parameter than SUV based on body weight in pediatric patients and is probably the most appropriate approach for the follow-up of these patients.

Using positron emission tomography with [(18)F]FDG to predict tumor behavior in experimental colorectal cancer.

This study investigates the relationship between FDG uptake as determined by positron emission tomography (PET) imaging and rates of tumor growth, cellular GLUT1 transporter density, and the activities of hexokinase and glucose-6-phosphatase in a solid tumor implant model. Five different human colorectal xenografts of different growth properties were implanted in athymic rats and evaluated by dynamic (18)F-FDG-PET. The phosphorylating and dephosphorylating activities of the key glycolytic enzymes, hexokinase and glucose-6-phosphatase, were measured in these tumor types by spectrophotometric assays and the expression of GLUT1 glucose transporter protein was determined by immunohistochemistry. Correlations among FDG accumulation, hexokinase activity, and tumor doubling time are reported in these colon xenografts. The results indicate that the activity of tumor hexokinase may be a marker of tumor growth rate that can be determined by (18)F-FDG-PET imaging. PET scanning may not only be a useful tool for staging patients for extent of disease, but may provide important prognostic information concerning the proliferative rates of malignancies.

Evaluation of 11C-colchicine for PET imaging of multiple drug resistance.

UNLABELLED: Overexpression of P-glycoprotein (P-gp) can confer multiple drug resistance (MDR) phenotype on cancer cells and tumors by reducing intracellular accumulation of various cytotoxic agents. Early diagnosis of MDR in the clinic will serve to improve the efficacy of chemotherapeutic intervention and the quality of life of patients. In this article we describe use of a positron-emitting MDR tracer, 11C-colchicine (CHC), to evaluate MDR by PET imaging. Unlike existing MDR tracers such as 99mTc-sestamibi, this compound is electroneutral, with biodistribution not affected by perturbations of membrane potential. METHODS: In vitro studies showed that resistance to CHC is correlated to resistance to Taxol (paclitaxel). The results of biodistribution experiments were found to be consistent with previously reported experiments with CHC labeled with other isotopes. On the basis of in vitro experiments with a series of drug-resistant variants of the human neuroblastoma BE (2)-C cell line, a mathematic model of 11C-CHC distribution in tumors was formulated. Dynamic PET 11C-CHC imaging experiments were performed with nude rats xenografted with the BE (2)-C-sensitive and -resistant strains. Each scan was accompanied by a transmissions scan and a static FDG scan. These scans allowed improved image localization. RESULTS: We observed an approximately 2-fold difference between 11C-CHC accumulation in sensitive and resistant tumors. Imaging data were analyzed using the mathematic model, and various parameters characterizing resistance could be identified and estimated. In particular, the parameter r, proportional to the level of resistance of the tumors, was obtained. We showed that the ratio of these r parameters determined from the sensitive and resistant tumors was identical to the ratio of CHC accumulation in the corresponding sensitive and resistant cell lines used for xenografting. CONCLUSION: These in vivo experiments provided additional evidence for the indirect effect of P-gp action on CHC-to-tubulin binding, which in turn determines CHC uptake in tumors. The significance of these findings and future plans is discussed.

Pilot clinical trial of 5-[125I]iodo-2'-deoxyuridine in the treatment of colorectal cancer metastatic to the liver.

UNLABELLED: The thymidine analog, 5-iodo-2'-deoxyuridine (IUdR), is incorporated in the DNA of cells in the S phase. When incorporated into DNA, short-range Auger electrons emitted by 125I-labeled IUdR can cause double-strand breaks, delivering a lethal radiation dose to the cell. We conducted therapeutic trial to evaluate[125I/131I]IUdR pharmacokinetics in liver metastases from colorectal cancer. Dosimetry, safety, and therapeutic potential were assessed. METHODS: Four patients were each infused with 5 mCi [125I]IUdR and 10 mCi [131I]IUdR through the sideport of a hepatic artery pump. Iodine-131 images were quantitated and used for pharmacokinetic studies. The radioactivity in the DNA of biopsy samples of tumor, normal liver and bone marrow, obtained 24 or 48 hr after injection, was counted. RESULTS: All patients had [125I]IUdR and [131I]IUdR uptake in tumor, with a biexponential clearance. Repeat injections in individual patients showed little variation in tumor uptake, especially in the slow clearance component. On planar images, no long-term retention was seen in bone marrow or other actively dividing normal tissues. Radioactivity in all tumor DNA samples was greater than background, while that in normal liver cell DNA was at background levels. Radioactivity in the DNA of one marrow sample taken at 24 hr was above background, but in another taken at 48 hr it was equal to background levels. No side effects were noted, no hematologic toxicity was observed in any patients and no tumor responses were seen. CONCLUSION: There is persistent uptake of [125I]IUdR in hepatic tumors, thereby making hepatic artery infusion a suitable mode of delivery for therapy. Repeat injections will be needed because only 15%-50% of tumor cells are in the S phase. Based on results from this pilot study, a therapeutic regimen is being planned.