[PET Research in Clinical Oncology].

Positron emission tomography (PET) in nuclear medicine is especially used for diagnosis in clinical oncology, and PET/CT examination using 18F-FDG is very useful for staging and therapy evaluation of cancer. The excellent property of PET diagnosis is that the functional information of cells can be evaluated quantitatively, but it also has the problem that its quantitative value fluctuates depending on image reconstruction conditions and body movements/respiratory movements. In this paper, we summarize the PET research that has been conducted so far in clinical oncology, and also introduce our researches for improve the quantitativeness.

The clinical utility of phase-based respiratory gated PET imaging based on visual feedback with a head-mounted display system.

OBJECTIVE: We developed a new respiratory-gated positron emission tomography (PET) imaging method (RGV-PET) that phase-based respiratory gated PET imaging (RG-PET) combine with head-mounted display (HMD)-guided "visual feedback." The purpose of this study was to investigate whether RGV-PET is effective at improving the quantitative measurement of tracer uptake in tumors using the phase-based respiratory gating method. METHODS: Of the 41 enrolled patients with hepatobiliary or pancreatic cancer, 20 patients underwent RGV-PET and the remaining 21 patients underwent RG-PET. We measured the peak standardized uptake value (SUVpeak) of the primary lesion in each five bins obtained from both RG-PET and RGV-PET. The SUVpeak change rate calculated based on the ungated PET imaging. To evaluate the quantitative variation, the coefficient of variation of the SUVpeak change rate was compared between RG-PET and RGV-PET. In addition, we performed qualitative evaluation using visual score for the incidence of artifacts on four-dimensional-CT. RESULTS: The coefficient of variation of the average SUVpeak change rate in RGV-PET was 7.01 ± 4.43, which was significantly lower than the values in RG-PET (10.72 ± 5.74, p < 0.05). A significant improvement in the SUVpeak change rate of RGV-PET was obtained in bins 1 and 2 compared to RG-PET ( p < 0.05). The visual score of RGV-PET was significantly lower than RG-PET ( p < 0.05). CONCLUSION: RGV-PET was effective for respiratory stabilization and improved respiratory gating imaging quality. ADVANCES IN KNOWLEDGE: The RGV-PET is applicable to various PET/CT respiratory gating imaging and may improve the quantitativeness of PET images.

Verification of the tumor volume delineation method using a fixed threshold of peak standardized uptake value.

We aimed to determine the difference in tumor volume associated with the reconstruction model in positron-emission tomography (PET). To reduce the influence of the reconstruction model, we suggested a method to measure the tumor volume using the relative threshold method with a fixed threshold based on peak standardized uptake value (SUVpeak). The efficacy of our method was verified using 18F-2-fluoro-2-deoxy-D-glucose PET/computed tomography images of 20 patients with lung cancer. The tumor volume was determined using the relative threshold method with a fixed threshold based on the SUVpeak. The PET data were reconstructed using the ordered-subset expectation maximization (OSEM) model, the OSEM + time-of-flight (TOF) model, and the OSEM + TOF + point-spread function (PSF) model. The volume differences associated with the reconstruction algorithm (%VD) were compared. For comparison, the tumor volume was measured using the relative threshold method based on the maximum SUV (SUVmax). For the OSEM and TOF models, the mean %VD values were -0.06 ± 8.07 and -2.04 ± 4.23% for the fixed 40% threshold according to the SUVmax and the SUVpeak, respectively. The effect of our method in this case seemed to be minor. For the OSEM and PSF models, the mean %VD values were -20.41 ± 14.47 and -13.87 ± 6.59% for the fixed 40% threshold according to the SUVmax and SUVpeak, respectively. Our new method enabled the measurement of tumor volume with a fixed threshold and reduced the influence of the changes in tumor volume associated with the reconstruction model.

Evaluation of a new motion correction algorithm in PET/CT: combining the entire acquired PET data to create a single three-dimensional motion-corrected PET/CT image.

PURPOSE: This study evaluated the potential of Q.Freeze algorithm for reducing motion artifacts, in comparison with ungated imaging (UG) and respiratory-gated imaging (RG). PATIENTS AND METHODS: Twenty-nine patients with 53 lesions who had undergone RG F-FDG PET/CT were included in this study. Using PET list mode data, five series of PET images [UG, RG, and QF images with an acquisition duration of 3 min (QF3), 5 min (QF5), and 10 min (QF10)] were reconstructed retrospectively. The image quality was evaluated first. Next, quantitative metrics [maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), SD, metabolic tumor volume, signal to noise ratio, or lesion to background ratio] were calculated for the liver, background, and each lesion, and the results were compared across the series. RESULTS: QF10 and QF5 showed better image quality compared with all other images. SUVmax in the liver, background, and lesions was lower with QF10 and QF5 than with the others, but there were no statistically significant differences in SUVmean and the lesion to background ratios. The SD with UG and RG was significantly higher than that with QF5 and QF10. The metabolic tumor volume in QF3 and QF5 was significantly lower than that in UG. CONCLUSION: The Q.Freeze algorithm can improve the quality of PET imaging compared with RG and UG.

[Application of the PET for Radiation Therapy].

Because radiotherapy is local treatment, it is very important to define target volume and critical organs based on accurate lesion area. The PET using an index such as the SUV is quantifiable noninvasively with information of the molecular biology for individual case/lesion. In particular, PET with 18F-fluorodeoxyglucose (FDG-PET) has been used for the diagnosis and treatment evaluation of various tumors. The radiation therapy based on PET enables the treatment planning that reflected metabolic activity of the lesion. The PET produce an error by various factors, therefore, we must handle the PET image in consideration of this error when apply PET to radiotherapy.

Amyloid imaging mismatch.

An 82-year-old man with suspected systemic amyloidosis and complete atrioventricular block underwent vascular biopsy during his pacemaker implantation with pathology showing amyloid deposits. 99mTc-aprotinin SPECT revealed increased radiotracer uptake along the left ventricular wall, consistent with cardiac amyloidosis. 11C-PiB PET/CT performed for the evaluation of amyloid deposits in the brain showed findings suggestive of Alzheimer disease without abnormal radiotracer concentration in the myocardium to match the 99mTc-aprotinin SPECT findings. Dynamic PET images showed increased 11C-PiB concentration in the left ventricular myocardium at 2 minutes after injection, with subsequent tracer clearance by approximately 5 minutes, consistent with normal 11C-PiB biodistribution.

Reevaluation of FDG-PET/CT in patients with hoarseness caused by vocal cord palsy.

OBJECTIVE: Vocal cord palsy (VCP) is a potential cause of hoarseness that results in decreasing mobility of the vocal cord. VCP can arise from a variety of causes; so, systematic screening is warranted for the management of patients with VCP. Asymmetrical fluorodeoxyglucose (FDG) uptake in vocal cords is a well-known feature in patients with VCP, but no detailed analysis has been performed. This study aimed at reevaluating the (18)F-FDG positron emission tomography/computed tomography (PET/CT) for patients with VCP. METHODS: We retrospectively surveyed the results of FDG-PET/CT for 59 patients with VCP, compared to laryngoscopic findings. Quantitative analysis was performed using maximum standardized uptake value (SUVmax), and regions of interest were drawn over bilateral vocal cords as confirmed from the CT portion of PET/CT. Patients were divided into 3 groups: Group 1 (n = 14), in which VCP was caused by the lesion of the laryngeal area; Group 2 (n = 40), in which VCP was caused by the lesion on the root of the recurrent laryngeal nerve; and Group 3 (n = 5), in which VCP was caused by the lesion from the vagal center to the proximal vagus nerve. RESULTS: For Group 1, higher FDG uptake in the paralyzed vocal cord was seen in 86 % of patients (mean SUVmax 8.1 ± 5.3 vs. 2.3 ± 0.4, paralyzed vs. non-paralyzed, respectively; P < 0.002). The sensitivity of FDG-PET/CT for indicating the lesion causing VCP was 79 % for Group 1. Group 2 showed dominant FDG uptake in the non-paralyzed vocal cord (mean SUVmax 2.1 ± 0.9 vs. 1.5 ± 0.4, non-paralyzed vs. paralyzed, respectively; P < 0.001). The sensitivity of FDG-PET/CT for indicating the lesion causing VCP was 93 % for Group 2. Group 3 showed no statistically significant difference in FDG accumulation between non-paralyzed and paralyzed vocal cords (mean SUVmax 1.8 ± 0.3 vs. 1.7 ± 0.3, non- paralyzed vs. paralyzed, respectively; P = 0.30). The sensitivity of FDG-PET/CT for indicating the lesion causing VCP was 60 % for Group 3. CONCLUSIONS: FDG accumulation in the vocal cords is dependent on the lesion site causing VCP. In addition, FDG-PET/CT can contribute to identification of the lesion responsible for inducing VCP.

Validation for performing ¹¹C-methionine and ¹8F-FDG-PET studies on the same day.

BACKGROUND AND OBJECTIVE: The performance of two PET examinations, one using L-[methyl-¹¹C] methionine (MET) and one using 2-[¹8F] fluoro-2-deoxy-D-glucose (FDG), on the same day may offer a clinical advantage for the investigation of brain tumors or other lesions. The purpose of this study was to investigate the effect of positron cross-talk (PCT) and to determine the optimal protocol for using MET and FDG on the same day. METHODS: The participants comprised 62 patients with head and neck cancer. We focused on the high physiological uptake of MET in the liver and evaluated the effect of PCT with MET on FDG uptake in the liver and muscle. Three FDG-PET scans [one: whole body (early image), two: head and neck, and three: one-bed-position scan of the liver (delayed image)] were performed after completing a MET-PET scan (head and neck) at varying injection intervals. Standard uptake value mean variations in the liver and muscle were calculated, assuming that the differences between the early and the delayed images reflected the PCT from carbon-11 on fluorine-18, on the basis of the results of a phantom study and a study in volunteers. The participants were categorized into four groups (G) according to the injection interval: G1 (n=15, 30-49 min), G2 (n=16, 50-69 min), G3 (n=17, 70-89 min), and G4 (n=14, ≥ 90 min). RESULTS: The PCT level decreased from the G1 group through to the G3 group (analysis of variance, P<0.001) but was stable, with no further decrease in the G4 group. The PCT level in the muscle was not significantly different among the G1, G2, G3, and G4 groups (analysis of variance, P=0.693). Thus, PCT in the liver decreased at longer injection intervals, and PCT was no longer observed at injection intervals of more than 90 min. CONCLUSION: MET and FDG-PET examinations can be successfully performed on the same day without PCT between the studies if the injection interval is longer than 90 min. This method reduces the examination burden of patients and may be useful for performing multiple PET examinations while the patient's condition remains almost the same.

4'-[Methyl-11C]-thiothymidine PET/CT for proliferation imaging in non-small cell lung cancer.

UNLABELLED: A new tracer, 4'-[methyl-(11)C]-thiothymidine ((11)C-4DST), has been developed as an in vivo cell proliferation marker based on the DNA incorporation method. This study evaluated the potential of (11)C-4DST PET/CT for imaging proliferation in non-small cell lung cancer (NSCLC), compared with (18)F-FDG PET/CT. METHODS: Eighteen patients with lung lesions were examined by PET/CT using (11)C-4DST and (18)F-FDG. We constructed decay-corrected time-activity curves of 9 major regions as the mean standardized uptake value. We then compared the maximum standardized uptake value (SUVmax) of lung tumors on both (11)C-4DST and (18)F-FDG PET/CT with the Ki-67 index of cellular proliferation and with CD31-positive vessels as a marker of angiogenesis in surgical pathology. RESULTS: NSCLC was pathologically confirmed in 19 lesions of 18 patients. Physiologic accumulation of (11)C-4DST was high in liver, kidney, and bone marrow and low in aorta, brain, lung, and myocardium. Biodistribution of (11)C-4DST was almost stable by 20 min after injection of (11)C-4DST. Mean (11)C-4DST SUVmax for lung cancer was 2.9 ± 1.0 (range, 1.5-4.7), significantly different from mean (18)F-FDG SUVmax, which was 6.2 ± 4.5 (range, 0.9-17.3; P < 0.001). The correlation coefficient between SUVmax and Ki-67 index was higher with (11)C-4DST (r = 0.82) than with (18)F-FDG (r = 0.71). The correlation coefficient between SUVmax and CD31 was low with both (11)C-4DST (r = 0.21) and (18)F-FDG (r = 0.21), showing no significant difference between the tracers. CONCLUSION: A higher correlation with proliferation of lung tumors was seen for (11)C-4DST than for (18)F-FDG. (11)C-4DST PET/CT may allow noninvasive imaging of DNA synthesis in NSCLC.

Cut-off value for normal versus abnormal right-to-left shunt percentages using (99m)Tc-macroaggregated albumin.

OBJECTIVE: To determine the cut-off value for distinguishing a normal versus an abnormal right-to-left shunt percentage on lung perfusion scintigraphy using (99m)Tc-macroaggregated albumin (MAA). MATERIALS AND METHODS: Fifty-three patients (eight patients with a right-to-left shunt and 45 without a right-to-left shunt) who underwent MAA whole-body imaging for the evaluation of right-to-left shunts were divided into group 1 (eight patients with brain MAA uptake) and group 2 (45 patients without brain MAA uptake). Moreover, group 2 was subdivided into two categories (groups 2a and 2b) based on the results of lung computed tomography, electrocardiography examinations, and pulmonary function tests. The average and standard deviation (SD) of each group were compared. In addition, we estimated the cut-off value for a normal right-to-left shunt percentage using whole-body imaging. RESULTS: The average right-to-left shunt percentage values and SD were 23.67±12.17% in group 1, 6.68±1.04% in group 2a, and 6.60±0.84% in group 2b. The shunt percentages of groups 2a and 2b were not significantly different (P=0.77). The estimated normal value (mean±2 SD) of group 2 was 6.64±0.94%. Meanwhile, the cut-off value was estimated as 10% based on the distributions of MAA shunt percentages for groups 1 and 2. CONCLUSION: The normal range (mean±2 SD) was 6.64±1.88%. The cut-off value for the normal right-to-left shunt percentage in MAA scintigraphy was 10%.

Whole-body FDG-PET/CT on rheumatoid arthritis of large joints.

OBJECTIVE: Fluorodeoxyglucose (FDG) uptake in joint lesions in patients with rheumatoid arthritis (RA) reportedly represents the degree of synovial inflammation. Most previous studies have focused on small joints, and the application of whole-body positron emission tomography (PET) combined with computed tomography (CT) (PET/CT) for the evaluation of inflammatory activity in large joints has not been well studied. METHODS: Eighteen patients with RA underwent FDG-PET/CT. FDG uptake in the knee, hip, carpal, wrist, elbow, shoulder, and atlanto-axial joint (total of 13 joints) and in the axillary lymph nodes was evaluated by calculating the maximum standardized uptake value (SUV(max)) and the visual uptake scores as follows: 0, no uptake; 1, slight uptake; 2, moderate uptake (same as in liver); 3, higher than in liver; 4, highest uptake. The number of painful/swollen joints, the white blood cell (WBC) count, and the C-reactive protein (CRP) level were also evaluated. RESULTS: Whole-body FDG-PET/CT delineated large-joint lesions in patients with RA, and the metabolic activity of inflammation was accurately overlaid on the joint anatomy. The total FDG score for all 13 joints was significantly correlated with the CRP level (r = 0.653, p < 0.01, n = 18). The total SUV(max) and the CRP level were weakly, but not significantly, correlated (r = 0.377, p > 0.05). The WBC count was not correlated with any other parameter. The mean number of joints per patient with an FDG uptake score of 2 or more was significantly larger than the mean number of painful/swollen joints (6.2 +/- 3.3 vs. 3.1 +/- 2.7, n = 18, p < 0.01) and both parameters were strongly correlated (r = 0.588, p < 0.01, n = 18). Also, FDG uptake score and SUV of painful/swollen joints were significantly higher than these of not painful/swollen joints. FDG uptake was significantly different from patients of remission and patients of active arthritis. Uptake in the atlanto-axial joint was observed in five (mostly asymptomatic) patients (5/18, 28%), and the uptake score was significantly correlated with the total FDG score (r = 0.669, p < 0.01, n = 18). The axillary lymph nodes score was correlated with the arm joints score. CONCLUSION: FDG-PET/CT represents the inflammatory activity in large joints in patients with RA accurately and sensitively and may be helpful for early evaluations of the extent of RA throughout the whole body including high risk lesion of atlanto-axial joint. Furthermore, the visual FDG uptake score may be useful for evaluating arthritis in large joints.

11C-methionine PET of acute myocardial infarction.

UNLABELLED: Tissue uptake of l-[methyl-(11)C]-methionine ((11)C-methionine) has been used to monitor amino acid metabolism and protein synthesis. We examined whether (11)C-methionine was retained in areas of myocardial infarction after successful reperfusion. METHODS: Nine patients with infarction in the left anterior descendent region underwent percutaneous transluminal coronary artery intervention within 24 h and (201)Tl SPECT, (18)F-FDG PET, and (11)C-methionine PET within 2 wk of infarction onset. The standardized uptake values of the infarcted area and of the normal area were measured. RESULTS: The (11)C-methionine images showed increased uptake in the infarcted area, whereas the (201)Tl SPECT and (18)F-FDG PET images showed decreased uptake. The highest accumulation of (11)C-methionine in the infarcted area was observed during the early phase of AMI. CONCLUSION: (11)C-methionine uptake is elevated in infarcted areas and may reflect the early acute phase of damage healing, that is, the initial process of remodeling.

Scintigraphic detection of 125I seeds after permanent brachytherapy for prostate cancer.

UNLABELLED: The purpose of this investigation was to monitor the localization and migration of 125I seeds after permanent brachytherapy for prostate cancer using a new scintigraphic technique that may overcome the drawbacks of conventional x-ray methods. METHODS: 125I seeds emit gamma-rays with an average energy peak of 28 keV. We used a gamma-camera equipped with low-energy high-resolution collimators that were tuned to an energy level of 35 keV with a 70% window width. Sixteen patients with prostate cancer were examined after 125I seed insertion. The number of seeds remaining in the prostate was confirmed using pelvic CT for postoperative dose planning; however, seeds that had migrated outside the prostate could not be detected. Furthermore, the migrated seeds were not completely traceable using chest or abdominal radiography. Thus, we adopted a scintigraphic technique to perform this task. The evaluation of radiography and scintigraphy findings was masked, and the rates of migrated seed detection were statistically examined using the McNemar test. To localize the migrated seeds, we fused the scintigraphic images of the migrated seeds and the patients' contours. RESULTS: Scintigraphy was successfully used to detect 20 migrated seeds of a total of 1,182 implanted seeds, whereas radiography was successfully used to detect 7. The sensitivity of the scintigraphy results was 20 of 20 (100%), whereas that of the radiography results was 7 of 20 (35%). Seed migration was detected in 11 of 16 patients (69%) using scintigraphy, whereas seed migration was detected in only 4 patients (25%) using radiography; this difference was statistically significant (P = 0.016). CONCLUSION: Scintigraphy is more effective for detecting seed migration and monitoring the localization of 125I seeds than radiography. The precise anatomic location of migrated seeds can be pinpointed using fusion images. Scintigraphy may become a standard procedure for monitoring seed migration during 125I brachytherapy in patients with prostate cancer.