Assessment of [(18)F]-fluoroacetate PET/CT as a tumor-imaging modality: preclinical study in healthy volunteers and clinical evaluation in patients with liver tumor.

OBJECTIVE: Although [(18)F]-FDG is a useful oncologic PET tracer, FDG uptake is known to be low in a certain type of hepatocellular carcinoma (HCC). [(18)F]-fluoroacetate ((18)F-FACE) is an [(18)F] fluorinated acetate, which is known to be converted into fatty acids, incorporated in membrane and is expected to be a promising oncologic PET tracer. The aim of this study was to evaluate the usefulness of (18)F-FACE as an oncologic PET tracer in preclinical study in healthy volunteers and in patients with liver tumors. METHODS: Twenty-four healthy volunteers (age 48.2 ± 12.9 years old; 15 male and 9 female) and ten patients with liver tumor (age 72.1 ± 7.0 years old; 6 male and 4 female) were included. We performed whole-body static PET/CT scan using (18)F-FACE (n = 34) and (18)F-FDG (n = 5 for volunteers, n = 8 for patients) on each day, respectively. Qualitative analysis and quantitative analysis of tumors (5 HCCs, 1 cholangiocellular carcinoma, 4 metastatic tumors from colon cancer and P-NET) were performed using SUVmax and tumor-to-normal liver ratio (TNR). RESULTS: In healthy volunteers, (18)F-FACE was metabolically stable in vivo and its biodistribution was almost similar to blood pool, basically uniformly independent of age and gender during PET scan time (up to 3 h). Normal physiological uptake of (18)F-FACE at each organ including liver (SUVmean 1.8 ± 0.2) was lower than that of blood pool (SUVmean 2.3 ± 0.3) at 1 h after injection. Chronic inflammatory uptake around femur of post-operative state of femoral osteotomy and faint uptake of benign hemangioma were observed in a case of healthy volunteer. (18)F-FACE (SUVmax 2.7 ± 0.6, TNR 1.5 ± 0.4) of liver tumors was significantly lower than those of (18)F-FDG uptake (6.5 ± 4.2, 2.6 ± 1.7, respectively). In qualitative analysis, (18)F-FDG was positive in 4 tumors (3 HCCs, 1 CCC) and negative in the other 6 tumors, while (18)F-FACE was also positive in 4 tumors which were the same tumors with positive (18)F-FDG uptake. CONCLUSIONS: Biodistribution of (18)F-FACE was appropriate for oncologic imaging. Tumor (18)F-FACE uptake was positive in four patients with HCC and CCC, but the uptake pattern was similar to (18)F-FDG. Further evaluation was needed.

Clinical significance of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography for the assessment of 131I-metaiodobenzylguanidine therapy in malignant phaeochromocytoma.

PURPOSE: The aim of this study was to evaluate the significance of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in the assessment of the therapeutic response to 131I-metaiodobenzylguanidine (MIBG) in malignant phaeochromocytoma. METHODS: We reviewed the records of 11 patients (7 men and 4 women) with malignant phaeochromocytoma who underwent 131I-MIBG therapy (100-200 mCi). 18F-FDG PET and serum catecholamine assays were performed 3 months before and after the first dose of 131I-MIBG. FDG uptake was evaluated in the observed lesions using the maximum standardised uptake value (SUVmax). The average SUVmax of all lesions (ASUV) was calculated. If more than five lesions were identified, the average SUVmax of the five highest SUVmax (ASUV5) was calculated. The ratio of pre- and post-therapy values was calculated for the highest SUVmax (rMSUV), ASUV (rASUV), ASUV5 (rASUV5), CT diameter (rCT) and serum catecholamine (rCA). Responder (R) and non-responder (NR) groups were defined after a clinical follow-up of at least 6 months according to changes in symptoms, CT, magnetic resonance imaging (MRI) and 123I-MIBG scan. RESULTS: Post-therapy evaluation revealed five R and six NR patients. The size of the target lesions was not significantly different before and after therapy (p>0.05). However, ASUV and ASUV5 were significantly lower in the R group (rASUV 0.64±0.18, rASUV5 0.68±0.17) compared to the NR group (rASUV 1.40±0.54, rASUV5 1.37±0.61) (p<0.05). CONCLUSION: 18F-FDG PET can be potentially used to evaluate the response of malignant phaeochromocytoma to 131I-MIBG therapy.

Assessment of therapy response in lung cancer with ¹8F-α-methyl tyrosine PET.

OBJECTIVE: PET with a novel tracer, L-[3-¹8F]-α-methyl tyrosine (¹8F-FMT), has been studied in lung cancer. We evaluated ¹8F-FMT PET for therapy response in comparison with ¹8F-FDG PET. SUBJECTS AND METHODS: Eighteen patients with lung cancer underwent PET studies with ¹8F-FMT and FDG before and after chemoradiotherapy. Uptake of tracers was measured by standardized uptake value (SUV) in the primary tumor and the mediastinal lymph node. The ratio of the lymph node maximum SUV (SUV(max)) to that of the primary tumor and the SUV(max) of the primary tumor itself were correlated with the survival time estimated by Kaplan-Meier method. Metabolic response, as determined by the changes in the tracer uptake, was compared with Response Evaluation Criteria in Solid Tumors (RECIST) for therapy response. RESULTS: Agreement of therapeutic response evaluated by RECIST was noted in 10 (56%) of 18 patients evaluated with FDG PET and in 16 (89%) of 18 patients evaluated with ¹8F-FMT PET (p = 0.025). In nine patients with partial response, partial metabolic response was observed in eight (89%) by use of FDG PET and in nine (100%) by use of ¹8F-FMT PET. In nine patients with stable disease, stable metabolic disease was observed in two (22%) by use of FDG PET and in seven (78%) by use of ¹8F-FMT PET (p = 0.056). Fluorine-18-FMT PET revealed that the prognosis of the group with a lymph node-to-primary tumor SUV(max) ratio greater than or equal to 1 was significantly better than that in the group with a ratio of less than 1. CONCLUSION: Fluorine-18-FMT is a promising PET tracer for monitoring response to chemoradiotherapy and for predicting the prognosis of patients with lung cancer.

[Assessment of the efficacy, safety and pharmacokinetics of SKG-02 (recombinant human TSH) in postoperative diagnosis of well-differentiated thyroid cancer--a Japanese prospective, controlled, multicenter open-label study].

OBJECTIVE: This study sought to assess the safety, efficacy, impact on hypothyroid symptoms, and pharmacokinetics of SKG-02 (rhTSH, thyrotropin alfa) in the diagnostic follow-up of Japanese patients with well-differentiated thyroid carcinoma (WDTC). METHODS: Ten Japanese adults with WDTC were enrolled into a prospective, multicenter, open-label trial comparing diagnostic whole-body scintigraphy (dxWBS) and serum thyroglobulin (Tg) testing aided by SKG-02 versus these procedures aided by thyroid hormone withdrawal (THW). Patients were their own controls. Variables compared included scan set ability to detect radioiodine uptake by remnant or malignant thyroid tissue, scan set quality, diagnostic sensitivity of dxWBS and Tg testing alone or combined, frequency of hypothyroid signs/symptoms, and adverse events (AEs). SKG-02 pharmacokinetic variables including maximum concentration (Cmax), time to Cmax (Tmax) and the area under the time-concentration curve (AUC) were calculated. RESULTS: In a blinded evaluation by an independent committee of 3 nuclear medicine experts, 70% of SKG-02 dxWBS scan sets were rated "equivalent" (n = 7) or "superior" (n = 0) to their THW counterparts in ability to detect radioiodine uptake in healthy or malignant thyroid tissue. Therefore the study exceeded its primary endpoint of a 60% equivalence/superiority rate. SKG-02 Tg testing identified 3/3 cases of disease. Hypothyroid signs/symptoms were substantially more frequent during THW than during euthyroidism permitted by SKG-02 use. SKG-02 was well-tolerated, with no severe or serious drug-related AEs. Cmax was 240.8 +/- 65.9 microIU/ml, Tmax was 28.75 +/- 14.21 hr after the first SKG-02 injection, and AUC was 11,414 +/- 3,462 microIU hr/ml in 9 patients evaluable for pharmacokinetics. CONCLUSIONS: SKG-02 was safe and effective in the diagnostic follow-up of Japanese patients with WDTC, avoiding hypothyroid morbidity relative to THW. These and the pharmacokinetic findings were similar to those of overseas Phase III studies.

[Application of 18F-FDG PET for the assessment of early response to the treatment and prognosis of patients].

Positron emission tomography (PET) with [18F] fluoro-2-deoxy-D-glucose (FDG) is used for the diagnosis of various types of cancer. FDG-PET is used also for the assessment of therapeutic response as well as work-up of recurrence after therapy. Due to the characteristics of FDG-PET as an imaging tool, FDG-PET is supposed to be superior to the conventional imaging such as CT for the accurate assessment of the treatment response in patients with malignant lymphoma. Malignant lymphoma usually undergoes chemotherapy or chemoimmunotherapy as a treatment of stage III and IV patients. Recent advancement in the therapy of malignant lymphoma enables optional treatment strategies such as radioimmunotherapy with 90Y-labeled anti-CD20 monoclonal antibody or oral fludalabine for indolent non-Hodgkin's lymphoma and high-dose chemotherapy with autologous stem cell transplantation for aggressive non-Hodgkin's lymphoma. The purpose of the present study was to determine the clinical value of FDG-PET for the early assessment of therapeutic response of malignant lymphoma. Twenty-six patients with malignant lymphoma were enrolled in the study. The subject consists of 10 patients with follicular lymphoma, 9 diffuse large B-cell lymphoma, and others. Therapeutic regimens were rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 19 patients, CHOP and ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for 2 patients each, and others. FDG-PET was performed before the initiation of therapy in all patients and after the therapy of 1-2 courses in 5 patients; and 3-4 courses, 5-6 courses, and 7-8 courses in 7 patients each. Complete remission on the PET (CR(PET)) was defined as the FDG uptake lower than the background and compared with the final response assessment. CR(PET) was acquired in 4 of 5 patients at 1-2 courses, 6 of 7 at 3-4 courses, 4 of 7 at 5-6 courses, and 3 of 7 at 7-8 courses. In the group of 7-8 courses, final response assessment revealed 2 patients excess of CR. In patients who underwent multiple PET studies during the treatment, all 4 patients showed CR(PET) in its first assessment, and maintained CR thereafter. The present study revealed that most of the patients achieved CR(PET) up to 4 courses of therapy. The cases with remaining FDG uptake at this time were likely to be resistant to the therapy. The early assessment of therapeutic response may be accurately assessed by FDG-PET as early as 2 or 4 courses of therapy. Residual uptake of FDG in the lesion would be considered to be subject to the new therapeutic strategy. Clinical usefulness of the strategy based on the early response assessment with FDG-PET would be confirmed by the clinical trials.

Practical assessment of myocardial viability with a positron coincidence gamma camera using 18F-fluorodeoxyglucose in acute myocardial infarction: comparison with dedicated positron emission tomography and 201Tl single photon emission computed tomography.

OBJECTIVE: 2-[(18)F] fluoro-2-deoxy-D-glucose ((18)F-FDG) began to be supplied commercially to our hospital, which does not have a cyclotron, in autumn of 2005. The purpose of this study was to compare the utility of a dual-head positron coincidence detection (PCD) gamma camera in the detection of myocardial viability using (18)F-FDG with that of dedicated positron emission tomography (PET) and with that of thallium-201 ((201)Tl) single photon emission computed tomography (SPECT). METHODS: A total of 15 patients (14 men and 1 woman, mean age: 60+/-7 years, range: 46-73) with a large acute myocardial infarction (AMI) underwent (18)F-FDG PET, (18)F-FDG PCD imaging after oral glucose loading (75 g) and (201)Tl SPECT imaging. We divided the SPECT and PET images into a total of 20 segments, and semiquantitative visual analysis was performed by assessing regional tracer activities on a 4-point scoring system (DS): 0=normal uptake, 1=mildly reduced uptake, 2=severely reduced uptake, and 3=no uptake. We summed the DS in each patient as the total DS (TDS). RESULTS: The TDS of the (18)F-FDG PET image was 14.4+/-7.7. The TDS of the (18)F-FDG PCD image was 18.7+/-7.7. The TDS of the (201)Tl SPECT image was 24.1+/-11.5. The TDS of the (18)F-FDG PET image was significantly smaller than that of the (18)F-FDG PCD image. The TDS of the (18)F-FDG PET image was significantly smaller than that of the (201)Tl SPECT image. The TDS of the (18)F-FDG PCD image was significantly smaller than that of the (201)Tl SPECT image. CONCLUSION: The findings of the project suggest that (18)F-FDG PCD is a good modality based on its accuracy, convenience, and cost-performance for detecting myocardial viability in hospitals that do not have a PET system.

[Assessment for the image interpretation of 111In-ibritumomab tiuxetan in the phase II study of 90Y-ibritumomab tiuxetan in patients with relapsed or refractory indolent B-cell lymphoma].

Prior to the 90Y-ibritumomab tiuxetan (Y2B8) therapy, imaging is performed to verify the expected biodistribution of 111In-ibritumomab tiuxetan (In2B8). In order to determine the indication of radioimmunotherapy with Y2B8, the interpretation criteria for altered biodistribution of In2B8 was established. A phase II study of Y2B8 in patients with relapsed or refractory indolent B-cell lymphoma was performed in nine institutions in Japan. After the completion of the rituximab infusion at 250 mg/m2, 130 MBq of In2B8 was administered intravenously over 10 minutes. Gamma-camera imaging was performed at 2-24 hrs, 48-72 hrs, and 90-144 hrs. Images were interpreted by two investigators including a nuclear physician at the individual institution according to the protocol defined criteria to determine the indication of the radioimmunotherapy. Forty-seven cases were enrolled in the study, and 45 cases underwent In2B8 scintigraphy. After the completion of the study, central assessment of the scintigram was performed by three nuclear physicians according to both the criteria of the phase II study and the latest version of the package insert of Zevalin in the United States of America. Two cases were judged as altered biodistribution based on both criteria. They demonstrated diffusely increased bone marrow uptake. The protocol defined criteria revealed additional two cases with altered biodistribution. They showed increased splenic uptake with facilitated blood clearance without increase in the bone marrow uptake. They received Y2B8 and no increment in the adverse event was noted as compared with cases with expected biodistribution. Then this type of biodistribution was not considered altered biodistribution. Increased focal bone marrow uptake was noted in other two cases. They were also considered within the limit of expected biodistribution. The present study recommends the following criteria for altered biodistribution of In2B8. 1) Diffusely increased bone marrow uptake simulating the super scan on bone scintigraphy, 2) Prominent uptake in all of the liver, spleen, and bone marrow, 3) Uptake in the lung, kidney, and intestine without lymphoma higher than the liver.

Analysis models to assess cost effectiveness of the four strategies for the work-up of solitary pulmonary nodules.

BACKGROUND: To evaluate the role of computed tomography (CT) -guided needle biopsy and sodium iodide fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in the investigation of solitary pulmonary nodules (SPN), which are discovered on screening chest radiographs, and to determine the cost-effectiveness of these modalities. MATERIAL/METHODS: We have used decision-tree analysis models to assess the accuracy and cost-effectiveness of four strategies for the diagnosis and management of SPNs: CT alone strategy (baseline), CT plus FDG-PET strategy, CT plus FDG-PET plus CT-guided needle biopsy strategy, and CT plus CT-guided needle biopsy strategy. Reported values of prevalence of cancer, and sensitivity and specificity of each diagnostic modality were applied to the decision-tree models using Japanese health care costs. RESULTS: The prevalence of lung cancer among SPNs discovered on the lung cancer screening was less than 10%. In this prevalence, the strategies using CT-guided needle biopsy were the cost-effective alternatives to the CT alone strategy (cost saving was 436,470 yen - 456,478 yen per patient), and had higher accuracies (95-96% vs. 67%). Both effects were mainly the result of reducing the number of the candidates who undergo unnecessary thoracotomy for a benign SPN, and these results were true over a wide range of prevalence of cancer (0-55%). The cost saving and accuracy of the CT plus FDG-PET strategy (359,206 and 92%) were approaching to those of the strategies using CT-guided needle biopsy. CONCLUSIONS: The introduction of CT-guided needle biopsy and FDG-PET for the evaluation of SPNs, which are discovered on screening chest radiograph, is potentially cost-effective in Japan with high accuracy.

[Whether and under what conditions FDG-PET might be cost-effective in evaluating solitary pulmonary nodules depicted on lung cancer screening in Japan].

PURPOSE: To determine whether and under what conditions fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) may be cost-effective in evaluating solitary pulmonary nodules depicted on lung cancer screening in Japan. MATERIALS AND METHODS: Three decision models for differentiating lung cancer from benign nodules were compared: CT alone, PET alone, and CT plus PET. The various paths of each strategy were dependent on variables determined from a review of the medical literature. Costs were based on Japanese health insurance. RESULTS: The prevalence of lung cancer among solitary pulmonary nodules detected on lung cancer screening was less than 10%. For this prevalence, the CT-plus-PET model was the cost-effective alternative to the CT-alone model (cost savings were yen 64,000 per patient) and provided greater accuracy (0.90 vs. 0.84). Both of these effects were the result of reducing the number of candidates who undergo unnecessary CT-guided or bronchofiberscopic biopsies or thoracotomy for a benign pulmonary nodule. CONCLUSION: The CT-plus-PET strategy is accurate and cost-effective for the characterization of solitary pulmonary nodules detected on lung cancer screening in Japan.

Comparison between positron emission tomography and computed tomography in the use of the assessment of esophageal carcinoma.

BACKGROUND: The role and potential value of positron emission tomography (PET) scanning in certain tumors has been widely investigated in recent years. The authors retrospectively assessed the performance of 18-F-fluorodeoxyglucose (FDG)-PET in the assessment of esophageal squamous cell carcinoma (SCC). METHODS: The results using PET were compared with those using computed tomography (CT), and these were correlated with the pathologic findings. The authors studied 32 patients with thoracic esophageal SCC who had undergone radical esophagectomy. RESULTS: Uptake of FDG in the primary tumor was found in 25 of the 32 (78.1%) cases. Comparison of the FDG uptake and the clinicopathologic findings showed that there was a significant association between the FDG uptake and each of the depth of tumor invasion (P < 0.05), occurrence of lymph node metastasis (P < 0.01), and lymphatic invasion (P < 0.01). The survival rate in cases with high FDG uptake (standardized uptake value [SUV], >3) was significantly lower than that in cases with low FDG uptake (SUV, < 3; P < 0.05). In the evaluation of lymph node staging by the detection of lymph node metastasis, FDG-PET showed 77.8% sensitivity, 92.9% specificity, and 84.4% accuracy, and CT scanning showed 61.1% sensitivity, 71.4% specificity, and 65.6% accuracy. Positron emission tomography scanning showed a high degree of accuracy in the neck, upper thoracic, and abdominal regions. However, in the mid- and lower thoracic regions, the sensitivity was very low. The smallest lymph node metastasis that was detected by FDG-PET imaging was 6 mm. The average size of lymph node metastasis that was undetected by FDG-PET scanning was 7.3 mm (range, 1-17 mm). CONCLUSIONS: In conclusion, FDG-PET may be used as a noninvasive diagnostic technique in assessing the aggressiveness of the tumor and the prognosis in patients with esophageal SCC. During the preoperative diagnostic procedures, the sensitivity, specificity, and accuracy of lymph node staging is higher with FDG-PET than with CT imaging. In view of the high specificity of FDG-PET, it also gives useful information to guide the choice of treatment of esophageal carcinoma.