Imaging of Hypoxic Tumor: Correlation between Diffusion-weighted MR Imaging and 18F-fluoroazomycin Arabinoside Positron Emission Tomography in Head and Neck Carcinoma.

We investigated the usefulness of diffusion-weighted imaging (DWI) for detecting changes in the structure of hypoxic cells by evaluating the correlation between 18F-fluoroazomycin arabinoside (FAZA) positron emission tomography activity and DWI parameters in head and neck carcinoma. The diffusion coefficient corresponding to the slow compartment of a two-compartment model had a significant positive correlation with FAZA activity (ρ = 0.58, P = 0.016), whereas the diffusional kurtosis from diffusion kurtosis imaging had a significant negative correlation (ρ = -0.62, P = 0.008), which suggests that those DWI parameters might be useful as indicators for changes in cell structure.

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.

Prognostic value of PET/CT with (18)F-fluoroazomycin arabinoside for patients with head and neck squamous cell carcinomas receiving chemoradiotherapy.

OBJECTIVE: The prognostic value of positron emission tomography/computed tomography (PET/CT) with (18)F-fluoroazomycin arabinoside (FAZA) was evaluated in patients with head and neck squamous cell carcinoma (HNSCC) who underwent chemoradiotherapy (CRT). METHODS: Twenty-nine patients with head and neck cancer underwent FAZA PET/CT before treatment. Data acquisition started 2 h after FAZA administration. In 26 patients with squamous cell carcinoma, FAZA uptakes by the primary lesions (tumor-muscle ratio in primary lesion: Pr T/M) and by the lymph node metastases (tumor-muscle ratio in lymph node metastasis) were compared with various clinical parameters. For the HNSCC patients who completed CRT protocol (n = 23), those who experienced disease progression were compared with those who did not experience disease progression with respect to the clinical and PET parameters. The prognostic values of the clinical and PET parameters were then evaluated with regard to progression-free survival (PFS). RESULTS: Pr T/M positively correlated with the lesion's maximum diameter, and it was significantly higher in stage IV lesions compared with stage I-III lesions. No significant differences were observed between the patients who experienced disease progression and those who did not, with respect to the clinical parameters. The average Pr T/M tended to be higher in patients with disease progression, although the differences were not statistically significant (p = 0.086). Kaplan-Meier analysis with log-rank tests indicated that Pr T/M was an only significant predictor of PFS among PET and clinical parameters evaluated (p = 0.010). CONCLUSIONS: FAZA uptake by the primary lesion was a significant prognostic indicator in HNSCC patients undergoing CRT. Hence, FAZA PET/CT may provide useful information in the management of HNSCC patients treated with CRT. Registration number of clinical trial's registry: UMIN000003440.

Prognostic value of (18) F-fluoroazomycin arabinoside PET/CT in patients with advanced non-small-cell lung cancer.

This study evaluated the prognostic value of positron emission tomography/computed tomography (PET/CT) using (18) F-fluoroazomycin arabinoside (FAZA) in patients with advanced non-small-cell lung cancer (NSCLC) compared with (18) F-fluorodeoxyglucose (FDG). Thirty-eight patients with advanced NSCLC (stage III, 23 patients; stage IV, 15 patients) underwent FAZA and FDG PET/CT before treatment. The PET parameters (tumor-to-muscle ratio [T/M] at 1 and 2 h for FAZA, maximum standardized uptake value for FDG) in the primary lesion and lymph node (LN) metastasis and clinical parameters were compared concerning their effects on progression-free survival (PFS) and overall survival (OS). In our univariate analysis of all patients, clinical stage and FAZA T/M in LNs at 1 and 2 h were predictive of PFS (P = 0.021, 0.028, and 0.002, respectively). Multivariate analysis also indicated that clinical stage and FAZA T/M in LNs at 1 and 2 h were independent predictors of PFS. Subgroup analysis of chemoradiotherapy-treated stage III patients revealed that only FAZA T/M in LNs at 2 h was predictive of PFS (P = 0.025). The FDG PET/CT parameters were not predictive of PFS. No parameter was a significant predictor of OS. In patients with advanced NSCLC, FAZA uptake in LNs, but not in primary lesions, was predictive of treatment outcome. These results suggest the importance of characterization of LN metastases in advanced NSCLC patients.

Usefulness of 18F-fluorodeoxyglucose positron emission tomography as predictor of distant metastasis in preoperative carbon-ion radiotherapy for pancreatic cancer.

AIM: The purpose of this study was to evaluate the role of FDG-PET regarding the indication of preoperative carbon-ion radiotherapy (CIRT) for pancreatic cancer patients. PATIENTS AND METHODS: Patients with resectable pancreatic cancer underwent preoperative CIRT. The impact of baseline SUVmax on prognosis for patients was assessed by analyzing correlations with distant metastasis-free survival (DMFS) and overall survival (OS). RESULTS: Out of 21 patients, local recurrence was observed in no patient and distant metastasis was found in 13 patients (62%). 1-year DMFS and OS in low-SUVmax group were significantly higher than those in high-SUVmax group (91% vs. 20% and 91% vs. 56%). SUVmax was significantly correlated with DMFS and OS. CONCLUSION: Our data indicated a significant correlation between SUVmax and DMFS. FDG-PET might be useful for determining the indication of preoperative short-course CIRT for patients with resectable pancreatic cancer.

Accuracy of methionine-PET in predicting the efficacy of heavy-particle therapy on primary adenoid cystic carcinomas of the head and neck.

BACKGROUND: We evaluated whether or not PET or PET/CT using L-methyl-[11C]-methionine (MET) can allow for the early prediction of local recurrence and metastasis, as well as the prognosis (disease-specific survival), in patients with adenoid cystic carcinoma of the head and neck treated by carbon ion beam radiotherapy. METHODS: This was a retrospective cohort study of sixty-seven patients who underwent a MET-PET or PET/CT study prior to and one month after the completion of carbon ion radiotherapy (CIRT). The minimum follow-up period for survivors was 12 months. The MET accumulation of the tumor was evaluated using the semiquantitative tumor to normal tissue ratio (TNR). A univariate analysis was conducted using the log-rank method, and the Cox model was used in a multivariate survival regression analysis. RESULTS: The average TNR prior to and following treatment was 4.8 (±1.5) and 3.0 (±1.3), respectively, showing a significant decrease following treatment. In the univariate analysis, a high TNR prior to treatment (TNRpre) was a significant factor for predicting the occurrence of metastasis and the disease-specific survival. A high TNR following treatment (TNRpost) was a significant factor for predicting the development of local recurrence. The residual ratio of TNR changes (TNRratio) seemed to be less useful than the TNRpre. In the multivariate analysis, the TNRpost and tumor size were the factors found to significantly influence the risk of local recurrence. The TNRpre, TNRratio and tumor size were all significant factors influencing the occurrence of metastasis. Regarding the disease-specific survival, the TNRpre and age were the only factors with a significant influence on the outcome. CONCLUSIONS: The TNRpre was a factor that was significantly related to the occurrence of metastasis and the disease-specific survival after CIRT for adenoid cystic carcinoma of the head and neck. The TNRpost was a factor that was significantly related to the development of local recurrence. Thus, MET-PET or PET/CT can be useful for predicting or determining the therapeutic efficacy of CIRT.

Predictive value of 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography/computed tomography for outcome of carbon ion radiotherapy in patients with head and neck mucosal malignant melanoma.

OBJECTIVE: The purpose of this prospective study was to assess the prognostic value of 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) positron emission tomography/computed tomography (PET/CT) for the outcome of carbon ion radiotherapy (CIRT) in patients with mucosal malignant melanoma (MMM) of the head and neck. METHODS: Thirteen patients (69 ± 13 years) with histologically proven MMM tumor were enrolled. CIRT was performed with a total dose of 57.6-64.0 gray equivalents per 16 fractions over a period of 4 weeks. FLT-PET/CT was performed before and again 1 month after CIRT. Tumor FLT uptake was quantitatively assessed using the maximum standardized uptake value (SUV(max)). FLT-PET parameters [pre-CIRT SUV(max), post-CIRT SUV(max), and the reduction rate (RR)] and clinical parameters [age, gender, tumor site, tumor status, gross tumor volume (GTV), and regional lymph node involvement] were evaluated in relation to survival estimates. The follow-up period was 16.1 ± 5.9 months for 9 deceased patients, and 36.7 ± 7.9 months for 4 survivors. RESULTS: Pre-CIRT SUV(max) of ≥4.3, age of ≥80 years old, sinonasal cavity tumor site, and GTV of ≥39 mL were found to be statistically significant prognostic factors for better overall survival. Pre-CIRT SUV(max) of ≥5.0, age of ≥80 years old, sinonasal cavity tumor site, and the absence of regional lymph node involvement were statistically significant prognostic factors for better metastasis-free survival. RR of ≥35 % and GTV of <73 mL were predictive of better local control. CONCLUSIONS: The present study indicated for the first time that in patients with the head and neck MMM, FLT-PET/CT imaging was useful for predicting the therapeutic outcome of CIRT. Our results will contribute to the establishment of an effective staging system for MMM based on prognostic factors, depending on treatment choice.

PET/CT with 3'-deoxy-3'-[18F]fluorothymidine for lung cancer patients receiving carbon-ion radiotherapy.

OBJECTIVE: The aim of this study was to investigate the clinical value of 3'-deoxy-3'-[F]fluorothymidine-positron emission tomography/computed tomography (FLT-PET/CT) for lung cancer patients receiving carbon-ion radiotherapy. METHODS: Twenty consecutive patients with lung cancer underwent FLT-PET/CT before and after carbon-ion radiotherapy. Fifty minutes after intravenous injection of approximately 300 MBq of FLT, PET/CT data were acquired. Maximal standardized uptake value of the tumor was measured, from which the reduction rate of tumor FLT uptake was calculated. After treatment, the patients were followed (17-42 months for survivors) for the development of recurrence and survival. RESULTS: Primary responses to carbon-ion radiotherapy were partial in 13 patients, stable disease in six patients, and nonevaluable in one patient. Although tumor FLT uptake significantly decreased after treatment (P < 0.001), the presence of radiation pneumonitis hampered its precise evaluation. During the follow-up period, nine patients developed recurrence, and seven patients died including two deaths from other causes. Pretreatment FLT uptake of patients who developed recurrence and who died of lung cancer were significantly higher than that of patients who did not (P = 0.008 and 0.007, respectively). Kaplan-Meier analysis using a cut-off value also supported the prognostic value of pre-carbon-ion radiotherapy FLT-PET/CT. CONCLUSION: This investigation suggests that FLT-PET/CT is feasible in evaluating lung cancer patients undergoing carbon-ion radiotherapy. The presence of radiation pneumonitis can influence tumor FLT uptake and needs special attention. Pre-carbon-ion radiotherapy FLT-PET/CT seems to have a prognostic value and may contribute to decision-making on the treatment strategy.

Discrimination between low-grade oligodendrogliomas and diffuse astrocytoma with the aid of 11C-methionine positron emission tomography.

OBJECT: The diagnostic usefulness of (11)C-methionine PET scans in gliomas is still controversial. The authors investigated the clinical significance of (11)C-methionine PET findings in preoperative diagnosis of histological type and grade. METHODS: The tissue uptake of (11)C-methionine was assessed using PET in 70 patients with histologically confirmed intracerebral gliomas. The ratio of maximum standard uptake values in tumor areas to the mean standard uptake values in the contralateral normal brain tissue (tumor/normal tissue [T/N] ratio) was calculated and correlated with tumor type, histological grade, contrast enhancement on MR imaging, Ki 67 labeling index, and 1p/19q status. RESULTS: The T/N ratio was significantly increased as tumor grade advanced in astrocytic tumors (WHO Grade II vs Grade III, p = 0.0011; Grade III vs Grade IV, p = 0.0007). Among Grade II gliomas, the mean T/N ratio was significantly higher in oligodendroglial tumors than in diffuse astrocytomas (DAs) (p < 0.0001). All T/N ratios for oligodendroglial tumors were ≥ 1.46, and those for DA were consistently < 1.46, with the exception of 2 cases of gemistocytic astrocytoma. The Ki 67 labeling index significantly correlated with T/N ratio in astrocytic tumors, but not in oligodendrogliomas. Oligodendroglial tumors without 1p/19q deletion had a significantly higher T/N ratio than those with the codeletion. In combination with Gd-enhanced MR imaging, 67% of nonenhanced tumors with a T/N ratio of ≥ 1.46 were proved to be Grade II oligodendrogliomas. CONCLUSIONS: These results clearly show that (11)C-methionine PET T/N ratios in Grade II oligodendrogliomas were higher than those in DAs independently of their proliferative activity. This information contributes to preoperative differential diagnoses of histological type, especially in suspected low-grade gliomas.

Uptake decrease of proliferative PET tracer 18FLT in bone marrow after carbon ion therapy in lung cancer.

PURPOSE: The aim of this study was to investigate the change of 3'-[¹8F]fluoro-3'-deoxy-L: -thymidine (¹8FLT) uptake in normal bone marrow (BM) after inevitable radiation. PROCEDURES: Twenty-one non-small cell lung cancer patients who received carbon ion radiotherapy (CIRT) were studied with ¹8FLT-positron emission tomography/computed tomography (PET/CT) at pre- and post-CIRT. Radiation dose was calculated by radiation planning. Irradiated BM was divided into three groups (<10% of maximum dose, 10-30%, and >30%). RESULTS: ¹8FLT uptake clearly decreased at >10% irradiated areas and mildly decreased at <10% areas. ¹8FLT uptake was lowest just after CIRT, somewhat increased at 3 months, and remained unchanged for more than 1 year. There was no significant difference between 10-30% and >30% areas. CONCLUSION: ¹8FLT revealed that BM function decreased by small dose such as <4.2-4.4 GyE/1 fraction of CIRT and is eradicated by >4.2-4.4 GyE/1 fraction.

Role of glucose metabolism and cellularity for tumor malignancy evaluation using FDG-PET/CT and MRI.

OBJECTIVE: Standardized uptake value (SUV) is affected by many factors. In that respect, the brain reference index (BRI: regions of interest of tumor/regions of interest of cerebellum) is one of the quantitative approaches to eliminate the variety of factors that affect SUV. MRI pulse sequence findings can also provide information about tissue cellularity. This information is useful for evaluating the malignancy of lesions. We evaluated the role of glucose metabolism and cellularity for the diagnosis of pancreatic tumor malignancy. METHOD: We performed a radionuclide 2-(18)F-fluoro-2-deoxyglucose ((18)F-FDG) uptake analysis and a signal intensity analysis using MRI on 16 presurgery patients with either proven or suspected pancreatic cancer. The tumor glucose metabolism was evaluated with SUV and BRI in an FDG-PET study. Tumor cellularity was determined with the MRI factors, apparent diffusion coefficient (ADC), T2 value and tumor to nontumor ratio of proton density. We compared these results with the pathological findings. RESULTS: SUV (= 0.855), BRI ( =0.875), and ADC ( =0.830) showed a larger the area under the curve than T2 value (= 0.582) and tumor to nontumor ratio of proton density ( = 0.786) according to the receiver operating characteristics analysis, and we therefore considered that these three factors were better indexes for the diagnosis of tumor malignancy. SUV and BRI had a high specificity. In contrast, ADC had a high sensitivity. CONCLUSION: The glucose metabolism with PET/CT and cellularity with MRI are different indexes for the diagnosis of tumor malignancy. Both provide necessary information for making an accurate diagnosis. Using both types of information may therefore help in obtaining a highly accurate diagnosis.

Endobronchial ultrasound-guided transbronchial needle aspiration for lymph node staging in patients with non-small cell lung cancer in non-operable patients pursuing radiotherapy as a primary treatment.

INTRODUCTION: Carbon ion radiotherapy (CIRT) is a promising modality with excellent localization and significant biologic effects on tumors. Nevertheless, success depends primarily on accurate staging before radiotherapy. Surgical interventions should be avoided in patients considered for CIRT because they usually have multiple comorbidities. The aim of this study was to evaluate the effectiveness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for lymph node staging in patients with non-small cell lung cancer before CIRT. METHODS: From April 2005 to December 2007, 49 patients with non-small cell lung cancer considered for CIRT with abnormal positron emission tomography-computed tomography (PET-CT) accumulations in the mediastinum and/or hilum were evaluated by EBUS-TBNA. The convex probe EBUS was used for EBUS-TBNA. RESULTS: There were 38 men and 11 women. Their mean age was 75.2 years (range: 55-87). Based on PET-CT, clinical staging was four with N1 disease, 42 with N2 disease, and three with N3 disease. By histology, 26 patients had adenocarcinoma, 19 had squamous cell carcinoma, and four had other histologies. All positive lymph nodes on PET-CT were aspirated (range: 1-5; average 2.55 lymph nodes/patient). EBUS-TBNA diagnosed 43 cases as N0 disease and as a result underwent CIRT. Forty of the 43 cases remained in stable condition without local recurrences (follow-up 6-46 months). The diagnostic accuracy of EBUS-TBNA for lymph node staging was 93.9%. CONCLUSIONS: EBUS-TBNA offers accurate minimally invasive lymph node staging in patients who are candidates for CIRT. EBUS-TBNA can be safely performed with a high diagnostic accuracy before CIRT.

A study on the prognostic evaluation of carbon ion radiotherapy for head and neck adenocarcinoma with C-11 methionine PET.

PURPOSE: Carbon ion radiotherapy (CIRT) has been developed, and a phase I/II CIRT trial has been conducted in patients with adenocarcinoma in the head and neck region. We evaluated whether the L-methyl [11C]-methionine (MET) uptake could be an early predictor for local recurrence, metastasis, and the prognosis in patients with adenocarcinoma in the head and neck region. METHODS: Twenty-six patients were prospectively studied by MET-positron emission tomography (PET) before and about 1 month after CIRT. The tumor MET uptake was measured with the semiquantitative tumor to normal tissue ratio (TNR). The tumor TNR and relevant clinical parameters were then evaluated by both univariate and multivariate analyses. RESULTS: The average TNRs before and after the treatment were 6.2 (± 2.2) and 3.9 (± 1.7), respectively, and significant differences were observed between them. In a univariate analysis, both local recurrence and metastasis were observed more frequently in the group with a higher TNR before and after the treatment than a lower TNR, and the prognosis was also poor. The cut-off values were 9.3, 4.9, and 5.1 before the treatment and 4.9, 4.2, and 4.3 after the treatment, respectively. In the rate of TNR changes before and after the treatment, metastasis was observed more frequently in the group with lower rates of change, and the prognosis was poor. The cut-off values for metastasis and prognosis determination were 18.0% and 16.9%, respectively. In a multivariate analysis, significant differences were observed for all relationships except for the relationship between the TNR before the treatment and local recurrence. Significant differences were observed for metastasis and prognosis in the rate of TNR changes before and after the treatment. CONCLUSIONS: The determination of treatment effectiveness using TNR in CIRT for head and neck adenocarcinoma is an independent factor for predicting local recurrence, the incidence of metastasis, and the prognosis. MET-PET is therefore considered to be useful for determining the treatment effectiveness in patients with head and neck adenocarcinoma undergoing CIRT.

Detection of bone metastases using diffusion weighted magnetic resonance imaging: comparison with (11)C-methionine PET and bone scintigraphy.

PURPOSE: We evaluated the ability of diffusion-weighted imaging (DWI) to detect bone metastasis by comparing the results obtained using this modality with those obtained using (11)C-methionine (MET) positron emission tomography (PET) and bone scintigraphy. MATERIALS AND METHODS: This retrospective study involved 29 patients with bone metastasis. DWI was obtained using a single-shot echo planar imaging (EPI) sequence with fat suppression using a short inversion time inversion recovery sequence. The detection capabilities of DWI for bone metastases were compared with those of whole body MET PET (in 19 patients) and 99mTc-methylene diphosphonate bone scintigraphy (in 15 patients). RESULTS: Among the 19 patients who were diagnosed using DWI and PET, the PET identified 39 bone metastases, while the DWI identified 60 metastases out of 69 metastases revealed with conventional magnetic resonance imaging (MRI). Among the 15 patients who were diagnosed using DWI and bone scintigraphy, the bone scintigraphy identified 18 bone metastases, while the DWI identified 72 metastases out of 78 metastases revealed with conventional MRI. The overall bone metastasis detection rates were 56.5% for PET, 23.1% for bone scintigraphy and 92.3% for DWI. CONCLUSION: DWI is a very sensitive method for detecting bone metastasis and is superior to MET PET and bone scintigraphy in terms of its detection capabilities.

Carbon-11-methionine PET imaging of choroidal melanoma and the time course after carbon ion beam radiotherapy.

UNLABELLED: The aim of this study was to assess the feasibility of MET-PET as an evaluation method of the therapeutic effect of carbon ion beam radiotherapy. PATIENTS AND METHODS: Twenty-four choroidal melanoma patients who were treated with a carbon ion beam underwent at least three MET-PET scans before and after therapy. The uptake was visually and semiquantitatively evaluated on the basis of the tumor-to-brain ratio (TBR). RESULTS: The accumulation was significantly decreased at 6 months or more after therapy and disappeared in 50% of the patients at 12 months after therapy. The baseline TBR, 1, 6, 12 and 24 months after therapy averaged 1.88+/-0.65, 1.73+/-0.52, 1.08+/-0.42, 0.67+/-0.27 and 0.65+/-0.30, respectively. TBR was significantly decreased at 6 months or more after therapy. CONCLUSION: MET-PET may be an alternative method for evaluating the effect of radiotherapy.

Molecular imaging of cancer: evaluating characters of individual cancer by PET/SPECT imaging.

The present status of cancer molecular imaging (MI) with nuclear medicine techniques is reviewed, highlighting the Japanese activities in this field. With the progress in MI research, including significant contributions from Japanese studies, it has become possible to noninvasively evaluate various important characters of cancer in clinical patients, such as metabolism, cellular proliferation, tumor hypoxia, and receptor expression. Tumor metabolic information is used for tumor characterization, treatment response evaluation, and prognosis prediction. Hypoxia imaging is used for treatment planning and predicting treatment response. Receptor imaging can be used for the selection of the candidate for receptor-targeted treatment. Various novel probes that can target cancer-associated antigens, various cellular growth factor receptors, tumor angiogenesis, and so on, are under development, aiming for clinical evaluation. Application of radiolabeled ligands for treatment (targeted internal radiation therapy) is another important field in which MI technique can play a critical role. MI, which can deliver the outcome of basic oncological research to the bedside, is essential translational research for improved individualized patient management, and further advances in MI studies are eagerly awaited.

Positron emission tomography for the diagnosis and management of patients with gastrointestinal malignancies.

F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) can play an important role in evaluating patients who have locally advanced diseases and in recurrence detection and restaging in patients who have gastrointestinal tract malignancies. Introduction of an integrated PET/CT system enabled the precise co-evaluation of function and morphology and improved the diagnostic ability of FDG-PET. Application of FDG-PET for treatment response evaluation and prognosis prediction is becoming important. Development of novel PET probes is expected to improve the characterization of individual cancer and to contribute to individualized patient management.