Visualization of tumor hypoxia and re-oxygenation after stereotactic body radiation therapy in early peripheral lung cancer: A prospective study.

BACKGROUND AND PURPOSE: In this study, fluoromisonidazole positron emission tomography (F-MISO PET/CT) was used to evaluate tumor hypoxia and re-oxygenation in patients with lung tumors treated with stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: Patients with T1-2 N0 lung cancer were included in this study. The prescribed dose was 48-52 Gy in four fractions. F-MISO PET/CT was performed twice, before SBRT and 1-3 days after the first irradiation. The maximum standardized uptake value (SUVmax) and tumor/muscle ratio (TMR) were evaluated as indicators of hypoxia. The threshold for hypoxia was defined as a TMR of 1.30 or more. RESULTS: Between 2016 and 2021, 15 patients were included. Pre-treatment tumor hypoxia was observed in nine tumors (60 %). TMR in all six tumors without pre-treatment hypoxia rose after single high-dose irradiation. In contrast, TMR in six of nine tumors with pre-treatment hypoxia dropped after irradiation, suggesting re-oxygenation. Although no local recurrence was noted, regional and/or distant relapses were seen in four patients (27 %). Of these, three had tumors with abnormal F-MISO uptake. The remaining patient had a tumor without signs of hypoxia on pre-treatment PET/CT. The 2-year progression free survival of patients with tumors with and without pre-treatment hypoxia were 30 % and 63 %, respectively (p = 0.319). CONCLUSION: Tumor hypoxia reduced after single high-dose irradiation. Tumor with F-MISO uptake seems to be an unfavorable prognostic factor in lung SBRT.

[The Questionnaire Survey of Japanese Practice and Environment for Targeted Radionuclide Therapy in 2021].

PURPOSE: Recently, the targeted radionuclide therapy (TRT) was urgently required to adapt the practice and environment because of the implementation of novel therapeutic radiopharmaceuticals such as alpha- and beta- radionuclides therapy. The present study aimed to clarify the questionnaire survey with the current situation (safety controls for workers and patients) at Japanese TRT facilities. METHODS: The massive questionnaire survey, 2 months from October to November 2021, was conducted among nationwide 251 facilities that have performed TRT in the past two years. The alpha- and beta- therapeutic radiopharmaceuticals were categorized and answered by one representative of the facility under anonymity. We analyzed the actual situation of each facility related to occupational exposure, radiation protection, contamination inspection, patient release criteria, and dosimetry for TRT. RESULTS: The survey response rate was 69.1% (174 facilities). About 75% of these facilities reported that they either follow the guidelines or take their own measures to reduce occupational exposure. The confirmed means of patient release criteria were 68.0% with the administered radioactivity and 87.2% with the ambient dose rate. The cold run was not performed for the first time at 15.0% and 10.0% of the facilities for ß- and α-emitting radionuclides, respectively. The facilities without attachment syringe shields were 39.2% for alpha-radionuclides therapy and 20.3% for beta-radionuclides therapy. CONCLUSION: We clarified the Japanese problem for TRT practice and environment by the questionnaire survey. Our findings indicated that the Japanese guidelines and manuals for TRT were not partly followed in the nationwide facilities.

The usefulness of the total metabolic tumor volume for predicting the postoperative recurrence of thoracic esophageal squamous cell carcinoma.

BACKGROUND: Induction or adjuvant therapies are not always beneficial for thoracic esophageal squamous cell carcinoma (ESCC) patients, and it is thus important to identify patients at high risk for postoperative ESCC recurrence. We investigated the usefulness of the total metabolic tumor volume (TMTV) for predicting the postoperative recurrence of thoracic ESCC. METHODS: We retrospectively analyzed the cases of 163 thoracic ESCC patients (135 men, 28 women; median age of 66 [range 34-82] years) treated at our hospital in 2007-2012. The TMTV was calculated from the fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in the primary lesion and lymph node metastases. The optimal cut-off values for relapse and non-relapse were obtained by the time-dependent receiver operating curve analyses. Relapse-free survival (RFS) was evaluated by the Kaplan-Meier method, and between-subgroup differences in survival were analyzed by log-rank test. The prognostic significance of metabolic parameters and clinicopathological variables was assessed by a Cox proportional hazard regression analysis. The difference in the failure patterns after surgical resection was evaluated using the χ2-test. RESULTS: The optimal cut-off value of TMTV for discriminating relapse from non-relapse was 3.82. The patients with a TMTV ≥3.82 showed significantly worse prognoses than those with low values (p < 0.001). The TMTV was significantly related to RFS (model 1 for preoperative risk factors: TMTV: hazard ratio [HR] =2.574, p = 0.004; model 2 for preoperative and postoperative risk factors: HR = 1.989, p = 0.044). The combination of the TMTV and cN0-1 or pN0-1 stage significantly stratified the patients into low-and high-risk recurrence groups (TMTV cN0-1, p < 0.001; TMTV pN0-1, p = 0.004). The rates of hematogenous and regional lymph node metastasis were significantly higher in the patients with TMTV ≥3.82 than those with low values (hematogenous metastasis, p < 0.001, regional lymph node metastasis, p = 0.011). CONCLUSIONS: The TMTV was a more significantly independent prognostic factor for RFS than any other PET parameter in patients with resectable thoracic ESCC. The TMTV may be useful for the identifying thoracic ESCC patients at high risk for postoperative recurrence and for deciding the patient management.

Automatic detection of primary and metastatic lesions on cervicothoracic region and whole-body bone using a uniform machine-learnable approach for [18F]-FDG-PET/CT image analysis.

We propose a method to detect primary and metastatic lesions with Fluorine-18 fluorodeoxyglucose (FDG) accumulation in the lung field, neck, mediastinum, and bony regions on the FDG-PET/CT images. To search for systemic lesions, various anatomical structures must be considered. The proposed method is addressed by using an extraction process for anatomical regions and a uniform lesion detection approach. The uniform approach does not utilize processes that reflect any region-specific anatomical aspects but has a machine-learnable framework. Therefore, it can work as a lesion detection process for a specific anatomical region if it machine-learns the specific region data. In this study, three lesion detection processes for the whole-body bone region, lung field, or neck-mediastinum region are obtained. These detection processes include lesion candidate detection and false positive (FP) candidate elimination. The lesion candidate detection is based on a voxel anomaly detection with a one-class support vector machine. The FP candidate elimination is performed using an AdaBoost classifier ensemble. The image features used by the ensemble are selected sequentially during training and are optimal for candidate classification. Three-fold cross-validation was used to detect performance with the 54 diseased FDG-PET/CT images. The mean sensitivity for detecting primary and metastatic lesions at 3 FPs per case was 0.89 with a 0.10 standard deviation (SD) in the bone region, 0.80 with a 0.10 SD in the lung field, and 0.87 with a 0.10 SD in the neck region. The average areas under the ROC curve were 0.887 with a 0.125 SD for detecting bone metastases, 0.900 with a 0.063 SD for detecting pulmonary lesions, and 0.927 with a 0.035 SD for detecting the neck-mediastinum lesions. These detection performances indicate that the proposed method could be applied clinically. These results also show that the uniform approach has high versatility for providing various lesion detection processes.

High 11 C-Methionine Uptake in a Parasellar Inflammatory Pseudotumor.

ABSTRACT: A 20-year-old man had left visual impairment and homonymous hemianopsia. MRI findings suggested enlargement of an optic glioma, because optic glioma was indicated by MRI 14 years earlier without a definite pathological diagnosis. 11 C-methionine (MET) PET showed high uptake in the tumor in the parasellar region. Transnasal endoscopic biopsy was performed, and an inflammatory pseudotumor (IPT) was diagnosed based on histopathological findings. High MET uptake in a parasellar IPT has apparently not been previously reported. Clinicians should be aware of the possibility of high MET uptake in IPT, because this image could provide an interpretation pitfall.

Usefulness of respiratory-gated PET acquisition during delayed 18F-FDG PET/CT scanning for patients with liver metastases.

OBJECTIVES: To assess respiratory-gated (RG) positron emission tomography (PET) acquisition for patients with liver metastases during delayed PET/computed tomography (CT) scanning with fluorine-18-fluorodeoxyglucose (18F-FDG). METHODS: Nineteen patients with liver metastases who had undergone early whole-body 18F-FDG PET/CT scans without the RG technique and delayed scans with the RG technique were retrospectively selected. The maximum standardized uptake value (SUVmax) of 41 liver lesions and the tumor-to-liver uptake ratios (TLRs) for these same lesions were compared among three data sets: early non-respiratory-gated (early non-RG) images, delayed non-respiratory-gated (delayed non-RG) images, and delayed respiratory-gated (delayed RG) images. In the delayed non-RG and delayed RG images, the improvements in the TLR, relative to the early non-RG images, were assessed according to lesion size. RESULTS: For liver lesions, the SUVmax of early non-RG, delayed non-RG, and delayed RG images were 6.58±2.34, 7.69±3.08, and 9.47±3.73, respectively. There were significant differences among the three images (P<0.01). The TLR of the delayed RG images was significantly higher than those of the early non-RG and delayed non-RG images (P<0.01). In the delayed RG images, the difference in the TLR improvement for lesions ≤10 mm in size was 15% higher than that for lesions >10 mm in size; in the delayed non-RG images, the difference in the TLR improvement for the same lesion categories was 6%. CONCLUSION: Delayed RG imaging improves the TLR, compared with early non-RG and delayed non-RG imaging, especially for small lesions. RG PET acquisition may be a promising protocol for assessing liver metastases on delayed PET/CT scans.

[Radiological Technology for Targeted Radionuclide Therapy].

Targeted radioisotope therapy (TRT) is a radiotherapy using radioisotope or drug incorporating it and has been used as a treatment for selectively irradiating cancer cells. In recent years, interest in TRT has increased due to improvements in radionuclide production technology, development of new drugs and imaging modalities, and improvements in radiation technology. In order to enhance the effect of TRT, measurement of individual radiation doses to tumor tissue and organs at risk is important using highly quantitative nuclear medicine images. In this paper, we present a review of literature on optimization of TRT, which is a new research area from the perspective of radiation technology.

The impact of the offset distance between the planning target volume and isocenter on irradiation time in TomoTherapy: A phantom study.

PURPOSE: The influence of the offset distance from treatment target to gantry isocenter (GIC) on the dosimetric parameter and irradiation time was investigated using TomoTherapy METHODS: The reference position was defined as the centers of both the I'mRT phantom and planning target volume (PTV) with a spherical of 4 cm diameter aligned with the GIC. The dose calculations were performed in two offset methods with 2 and 12 Gy/fr, Method 1. The PTV was moved from 0.0 to 12.5 cm along the RL direction and -5.0 to 5.0 cm along the AP direction (PTV offset), Method 2. The phantom was moved from 0.0 to -7.5 cm along the RL direction and -5.0 to 5.0 cm along the AP direction (Phantom offset). The maximum, minimum and mean doses, homogeneity index, conformity index, irradiation time, and monitor unit were compared. RESULTS: The irradiation times increased with increasing PTV offset. The increases in the irradiation time were 54.4% and 40.8% at PTV offsets of 12.5 cm along the RL direction for 2 and 12 Gy/fr, while the increases were 20.1% and 15.0% at a PTV offset of 5.0 cm along the AP direction. An increased irradiation time was not observed for the phantom offset. The offset didn't affect the other parameters. CONCLUSIONS: The PTV location offset of ≥5 cm from the GIC along the RL and AP axes increased the irradiation time; therefore, the PTV should be aligned with the GIC as much as possible to reduce the irradiation time on TomoTherapy.

[Development of Novel Immobilization Adapter for Head and Neck Radiotherapy with Low-attenuation Material].

PURPOSE: The dosimetric error due to immobilization devices has been highlighted by the AAPM Task Group 176. We developed a novel low-radiation-absorbent immobilization adaptor (HMA), which can be used with a Styrofoam headrest for head and neck region in radiotherapy. The purpose of this study was to investigate the impact of the HMA on the dose distribution and compare with a commercially released plastic adapter. METHODS: Computed tomography (CT) simulation and dose calculation on a treatment planning system (TPS) were performed by the use of HMA and the plastic adapter with a cylindrical phantom. Both the adapters were placed on the phantom upside and the attenuation rate was measured. Gantry angles were changed at every 1°interval from 0°to 50°for measurements. The measured dose was normalized by the value of 90°. The treatment equipment was TrueBeam (Varian medical systems); X-ray energies were set on 4, 6 and 10 MV, respectively. The measured attenuation rates were also compared with calculation results of TPS. RESULTS: The highest differences on attenuation rate of both the adapters were observed at a gantry angle of 32.0°; the differences were 3.0% at 4 MV, 2.7% at 6 MV and 3.0% at 10 MV, respectively, and lower absorption was HMA. TPS calculation results of monitor unit for the HMA were within 1.0% in each energy. CONCLUSION: The HMA was able to provide absorption dose and calculation errors lower than a commercially released adapter. It can also provide more accurate dose delivery for radiotherapy in head and neck because of the low absorption characteristics.

Registration accuracy with the low dose kilovoltage cone-beam CT: A phantom study.

OBJECTIVE: The aim of this study was to investigate low-dose kilovoltage cone-beam CT (kV-CBCT) for image-guided radiotherapy, with a particular focus on the accuracy of image registration with low-dose protocols. METHODS: Imaging doses were measured with a NOMEX semiconductor detector positioned at the front of head, thorax, and pelvis human body phantoms while kV-CBCT scans were acquired at different tube currents. Aspects of image quality (spatial resolution, noise, uniformity, contrast, geometric distortion, and Hounsfield unit sensitivity) and image registration accuracy using bone and soft tissue were evaluated. RESULTS: With preset and the lowest tube currents, the imaging doses were 0.16 and 0.08 mGy, 5.29 and 2.80 mGy, and 18.23 and 2.69 mGy for head, thorax, and pelvis, respectively. Noise was the only quality aspect directly dependent on tube current, being increased by 1.5 times with a tube current half that of the preset in head and thorax, and by 2.2 times with a tube current 1/8 of the preset in the pelvis. Accurate auto-bone matching was performed within 1 mm at the lowest tube current. The auto-soft tissue matching could not be performed with the lowest tube current; however, manual-soft tissue matching could still be performed within 2 mm or less. CONCLUSION: Noise was the only image quality aspect dependent on the imaging dose. Auto-bone and manual-soft tissue matching could still be performed at the lowest imaging dose. ADVANCES IN KNOWLEDGE: When optimizing kV-CBCT imaging dose, the impact on bone and soft tissue image registration accuracy should be evaluated.

[PET/CT Simulation for Radiation Therapy Planning].

18F-FDG PET/CT has an important role in radiation therapy planning. FDG PET/CT parameters such as standard uptake value and metabolic tumor volume provide important prognostic and predictive information. Importantly, FDG PET/CT for radiation planning has added biological information in defining the gross tumor volume (GTV) as well as involved nodal disease. Several studies have shown that PET has an impact on radiation therapy planning in an important proportion of patients.On the other hands, FDG PET/CT for radiation therapy planning has several limitations. First of all, the method to determine the optimal threshold of FDG PET/CT images that generates the best volumetric match to GTV is not established. The size of the GTV derived from FDG accumulation changes significantly depending on the threshold value, the threshold value can affect the clinical target delineation. Secondly, FDG is not a cancer-specific agent, and false positive findings in benign diseases have been reported. PET/CT simulation for radiation therapy planning requires cooperation of other professions and sufficient physical assessment.

Impact of the Lok-bar for High-precision Radiotherapy with Tomotherapy.

BACKGROUND/AIM: Patient immobilization systems are used to establish a reproducible patient position relative to the couch. In this study, the impact of conventional lok-bars for CT-simulation (CIVCO-bar) and treatment (iBEAM-bar) were compared with a novel lok-bar (mHM-bar) in tomotherapy. MATERIALS AND METHODS: Verification was obtained as follows: i. artifacts in CT images; ii. dose attenuation rate of lok-bar, compared to without lok-bar; and iii. dose differences between the calculated and measured absorbed doses. RESULTS: With the CIVCO-bar, there were obvious metal artifacts, while there were nearly no artifacts with the mHM-bar. The mean dose attenuation rates with the mHM-bar and iBEAM-bar were 1.31% and 2.28%, and the mean dose difference was 1.55% and 1.66% for mHM-bar and iBEAM-bar. CONCLUSION: Using the mHM-bar reduced artifacts on the CT image and improved dose attenuation are obtained. The lok-bar needs to be inserted as a structure set in treatment planning with tomotherapy.

Tumor Hypoxia Detected by 18F-fluoromisonidazole Positron Emission Tomography (FMISO PET) as a Prognostic Indicator of Radiotherapy (RT).

BACKGROUND/AIM: 18F-misonidazole positron emission tomography (FMISO PET)/computed tomography (CT) obtained before and during radiotherapy (RT) was analyzed as to whether it could predict clinical outcome. PATIENTS AND METHODS: Twenty-two patients were included. FMISO PET/ CT was performed twice before RT and at a dose of approximately 20 Gy/10 fractions. FMISO maximum standardized uptake values (SUVmax), the tumor-to-muscle ratios (T/M), and hypoxic volume (HV) in gross target volumes were measured. RESULTS: Of the 22 tumors, 18 had hypoxic areas (SUVmax ≥1.60) before RT. SUVmax, T/M, and HV on the first PET/CT were significantly correlated with initial tumor response, although the values during RT were not related to the response. The overall survival and loco-regional control rates of patients below cut-off values were significantly better than those above the cut-off values. CONCLUSION: Tumor hypoxia detected by FMISO PET/CT before RT may predict clinical outcome.

Practical calculation method to estimate the absolute boron concentration in tissues using 18F-FBPA PET.

PURPOSE: The purpose of this study was to establish a practical method to estimate the absolute boron concentrations in the tissues based on the standardized uptake values (SUVs) after administration of 4-borono-phenylalanine (BPA) using 4-borono-2-18F-fluoro-phenylalanine (18F-FBPA) PET. METHODS: Rat xenograft models of C6 glioma (n = 7, body weight 241 ± 28.0 g) were used for the study. PET was performed 60 min after intravenous injection of 18F-FBPA (30.5 ± 0.7 MBq). After the PET scanning, BPA-fructose (167.3 ± 18.65 mg/kg) was administered by slow intravenous injection to the same subjects. The rats were killed 60 min after the BPA injection and tissue samples were collected from the major organs and tumors. The absolute boron concentrations (unit: ppm) in the samples were measured by inductively coupled plasma optical emission spectrometry (ICP-OES). The boron concentrations in the tissues/tumors were also estimated from the 18F-FBPA PET images using the following formula: estimated absolute boron concentration (ppm) = 0.0478 × [BPA dose (mg/kg)] × SUV. The measured absolute boron concentrations (mBC) by ICP-OES and the estimated boron concentrations (eBC) from the PET images were compared. RESULTS: The percent difference between the mBC and eBC calculated based on the SUVmax was -5.2 ± 21.1% for the blood, -9.4 ± 22.3% for the brain, 1.6 ± 21.3% for the liver, -14.3 ± 16.8% for the spleen, -9.5 ± 27.5% for the pancreas, and 3.4 ± 43.2% for the tumor. Relatively large underestimation was observed for the lung (-48.4 ± 16.2%), small intestine (-37.8 ± 19.3%) and large intestine (-33.9 ± 11.0%), due to the partial volume effect arising from the air or feces contained in these organs. In contrast, relatively large overestimation was observed for the kidney (34.3 ± 29.3%), due to the influence of the high uptake in urine. CONCLUSIONS: The absolute boron concentrations in tissues/tumors can be estimated from the SUVs on 18F-FBPA PET using a practical formula. Caution must be exercised in interpreting the estimated boron concentrations in the lung, small intestine and large intestine, to prevent the adverse effects of overexposure, which could occur due to underestimation by partial volume effect using PET.

A novel radiation protection device based on tungsten functional paper for application in interventional radiology.

Tungsten functional paper (TFP), which contains 80% tungsten by weight, has radiation-shielding properties. We investigated the use of TFP for the protection of operators during interventional or therapeutic angiography. The air kerma rate of scattered radiation from a simulated patient was measured, with and without TFP, using a water-equivalent phantom and fixed C-arm fluoroscopy. Measurements were taken at the level of the operator's eye, chest, waist, and knee, with a variable number of TFP sheets used for shielding. A Monte Carlo simulation was also utilized to analyze the dose rate delivered with and without the TFP shielding. In cine mode, when the number of TFP sheets was varied through 1, 2, 3, 5, and 10, the respective reduction in the air kerma rate relative to no TFP shielding was as follows: at eye level, 24.9%, 29.9%, 41.6%, 50.4%, and 56.2%; at chest level, 25.3%, 33.1%, 34.9%, 46.1%, and 44.3%; at waist level, 45.1%, 57.0%, 64.4%, 70.7%, and 75.2%; and at knee level, 2.1%, 2.2%, 2.1%, 2.1%, and 2.1%. In fluoroscopy mode, the respective reduction in the air kerma rate relative to no TFP shielding was as follows: at eye level, 24.8%, 30.3%, 34.8%, 51.1%, and 58.5%; at chest level, 25.8%, 33.4%, 35.5%, 45.2%, and 44.4%; at waist level, 44.6%, 56.8%, 64.7%, 71.7%, and 77.2%; and at knee level, 2.2%, 0.0%, 2.2%, 2.8%, and 2.5%. The TFP paper exhibited good radiation-shielding properties against the scattered radiation encountered in clinical settings, and was shown to have potential application in decreasing the radiation exposure to the operator during interventional radiology.

MEASUREMENT OF ABSORPTION DOSE OUTSIDE IRRADIATION FIELD IN IMRT.

The absorption dose outside the irradiation field for prostate intensity-modulated radiation therapy was measured and evaluated by comparison with calculated values of radiation treatment planning system (TPS). The values of TPS calculated were using Varian CLINAC21EX/Eclipse and TomoTherapy Planning System for constant irradiation time. The absorption dose was measured by placing a glass-element dosemeter in a human-bone enclosure phantom with a planning target volume inside the irradiation field. The organs at risk were the rectum, spinal cord, thyroid, eyeball and the left lung. The calculated values of TPS, Varian CLINAC21EX/Eclipse and TomoTherapy Planning System were calculated, up to 17 and 55 cm from the isocenter, respectively. The absorbed dose outside the irradiation field diverged with increased distance from the isocenter (Varian/Eclipse: p = 0.03, TomoTherapy Planning System: p = 0.25). The calculated values for the absorbed dose outside the irradiation field were underestimated.

Heterogeneity of intratumoral (111)In-ibritumomab tiuxetan and (18)F-FDG distribution in association with therapeutic response in radioimmunotherapy for B-cell non-Hodgkin's lymphoma.

BACKGROUND: The purpose of this study was to quantitatively evaluate the tumor accumulation and heterogeneity of (111)In-ibritumomab tiuxetan (Zevalin®) and tumor accumulation of (18)F-fluoro-deoxyglucose (FDG) and compare them to the tumor response in B-cell non-Hodgkin's lymphoma patients receiving (90)Y-ibritumomab tiuxetan (Zevalin®) therapy. METHODS: Sixteen patients with histologically confirmed non-Hodgkin's B-cell lymphoma who underwent (90)Y-ibritumomab tiuxetan therapy along with (111)In-ibritumomab tiuxetan single-photon emission computerized tomography (SPECT)/CT and FDG positron emission tomography (PET)/CT were enrolled in this retrospective study. On pretherapeutic FDG PET/CT images, the maximum standardized uptake value (SUVmax) was measured. On SPECT/CT images, a percentage of the injected dose per gram (%ID/g) and SUVmax of (111)In-ibritumomab tiuxetan were measured at 48 h after its administration. The skewness and kurtosis of the voxel distribution were calculated to evaluate the intratumoral heterogeneity of tumor accumulation. As another intratumoral heterogeneity index, cumulative SUV-volume histograms describing the percentage of the total tumor volume above the percentage thresholds of pretherapeutic FDG and (111)In-ibritumomab tiuxetan SUVmax (area under the curve of the cumulative SUV histograms (AUC-CSH)) were calculated. All lesions (n = 42) were classified into responders and non-responders lesion-by-lesion on pre- and post-therapeutic CT images. RESULTS: A positive correlation was observed between the FDG SUVmax and accumulation of (111)In-ibritumomab tiuxetan in lesions. A significant difference in pretherapeutic FDG SUVmax was observed between responders and non-responders, while no significant difference in (111)In-ibritumomab tiuxetan SUVmax was observed between the two groups. In contrast, voxel distribution of FDG demonstrated no significant differences in the three heterogeneity indices between responders and non-responders, while (111)In-ibritumomab tiuxetan demonstrated skewness of 0.58 ± 0.16 and 0.73 ± 0.24 (p < 0.05), kurtosis of 2.39 ± 0.32 and 2.78 ± 0.53 (p < 0.02), and AUC-CSH of 0.37 ± 0.04 and 0.34 ± 0.05 (p < 0.05) for responders and non-responders. CONCLUSIONS: Pretherapeutic FDG accumulation was predictive of the tumor response in (90)Y-ibritumomab tiuxetan therapy. The heterogeneity of the intratumoral distribution rather than the absolute level of (111)In-ibritumomab tiuxetan was correlated with the tumor response.

FBPA PET in boron neutron capture therapy for cancer: prediction of (10)B concentration in the tumor and normal tissue in a rat xenograft model.

BACKGROUND: Boron neutron capture therapy (BNCT) is a molecular radiation treatment based on the (10)B (n, α) (7)Li nuclear reaction in cancer cells, in which delivery of (10)B by 4-borono-phenylalanine conjugated with fructose (BPA-fr) to the cancer cells is of critical importance. The PET tracer 4-borono-2-(18) F-fluoro-phenylalanine (FBPA) has been used to predict the accumulation of BPA-fr before BNCT. However, because of the difference in chemical structure between BPA-fr and FBPA and the difference in the dose administered between BPA-fr (therapeutic dose) and FBPA (tracer dose), the predictive value of FBPA PET for BPA-fr accumulation in the tumor and normal tissues is not yet clearly proven. We conducted this study to validate FBPA PET as a useful test to predict the accumulation of BPA-fr in the tumor and normal tissues before BNCT. METHODS: RGC-6 rat glioma cells (1.9 × 10(7)) were implanted subcutaneously in seven male F344 rats. On day 20 after the tumor implantation, dynamic PET scan was performed on four rats after injection of FBPA for 1 h. Whole-body PET/CT was performed 1 h after intravenous injection of the FBPA solution (30.5 ± 0.7 MBq, 1.69 ± 1.21 mg/kg). PET accumulation of FBPA in the tumor tissue and various normal tissues was estimated as a percentage of the injected dose per gram (%ID/g). One hour after the PET/CT scan, BPA-fructose (167.32 ± 18.65 mg/kg) was injected intravenously, and the rats were dissected 1 h after the BPA-fr injection. The absolute concentration of (10)B in the autopsied tissues and blood was measured by inductively coupled plasma optical emission spectrometry (ICP-OES). RESULTS: The highest absolute concentration of (10)B determined by ICP-OES was found in the kidney (4.34 ± 0.84 %ID/g), followed by the pancreas (2.73 ± 0.63 %ID/g), and the tumor (1.44 ± 0.44 %ID/g). A significant positive correlation was found between the accumulation levels of BPA-fr and FBPA (r = 0.91, p < 0.05). CONCLUSIONS: FBPA PET can reliably predict accumulation of BPA-fr in the tumor as well as normal tissues.

Quantitative evaluation of cerebral blood flow and oxygen metabolism in normal anesthetized rats: 15O-labeled gas inhalation PET with MRI Fusion.

UNLABELLED: PET with (15)O gas has been used for the quantitative measurement of cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO(2)), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) in humans. However, several technical difficulties limit its use in experiments on small animals. Herein, we describe the application of the (15)O gas steady-state inhalation method for normal anesthetized rats. METHODS: Eight normal male Sprague-Dawley rats (mean body weight ± SD, 268 ± 14 g) under anesthesia were investigated by (15)O-labeled gas PET. After tracheotomy, an airway tube was placed in the trachea, and the animals were connected to a ventilator (tidal volume, 3 cm(3); frequency, 60/min). The CBF and OEF were measured according to the original steady-state inhalation technique under artificial ventilation with (15)O-CO(2) and (15)O-O(2) gases delivered through the radioactive gas stabilizer. CBV was measured by (15)O-CO gas inhalation and corrected for the intravascular hemoglobin-bound (15)O-O(2). Arterial blood sampling was performed during each study to measure the radioactivity of the whole blood and plasma. MR image was performed with the same acrylic animal holder immediately after the PET. Regions of interest were placed on the whole brain of the PET images with reference to the semiautomatically coregistered PET/MR fused images. RESULTS: The data acquisition time for the whole PET experiment in each rat was 73.3 ± 5.8 (range, 68-85) min. In both the (15)O-CO(2) and the (15)O-O(2) studies, the radioactivity count of the brain reached a steady state by approximately 10 min after the start of continuous inhalation of the gas. The quantitative PET data of the whole brain were as follows: CBF, 32.3 ± 4.5 mL/100 mL/min; CMRO(2), 3.23 ± 0.42 mL/100 mL/min; OEF, 64.6% ± 9.1%; and CBV, 5.05 ± 0.45 mL/100 mL. CONCLUSION: Although further technical improvements may be needed, this study demonstrated the feasibility of quantitative PET measurement of CBF, OEF, and CMRO(2) using the original steady-state inhalation method of (15)O-CO(2) and (15)O-O(2) gases and measurement of CBV using the (15)O-CO gas inhalation method in the brain of normal anesthetized rats.

Fluorodeoxyglucose uptake in the bone marrow after granulocyte colony-stimulating factor administration in patients with non-Hodgkin's lymphoma.

PURPOSE: To clarify the change in the fluorodeoxyglucose (FDG) uptake by the bone marrow over time after administration of granulocyte colony-stimulating factor (G-CSF), we evaluated the correlation between the interval from the last day of administration of G-CSF to positron emission tomography/computed tomography (PET/CT) study and spinal bone marrow accumulation in patients with non-Hodgkin's lymphoma. METHODS: A total of 127 patients with confirmed non-Hodgkin's lymphoma who underwent FDG PET within 60 days from the last administration of G-CSF were retrospectively reviewed. Thirty age-matched and sex-matched healthy controls were also included to evaluate physiological FDG uptake. PET/CT examinations were retrospectively reviewed, and maximum standardized uptake value (SUVmax) was measured by placing volumetric regions of interest over each thoracic and lumbar vertebra on PET images referring to CT images. Bone marrow SUV was defined as the mean SUVmax of the vertebra. The correlation between the interval after G-CSF and the bone marrow SUV was plotted and analyzed with polynomial approximation. RESULTS: In controls, physiological bone marrow SUV of the spine was determined. In patients with lymphoma, bone marrow SUV decreased over time and reached a plateau at about 14 days after G-CSF administration, and this was higher by 5% than the plateau at 10 days. SUV declined to the 'physiological range', that is, mean+1 standard deviation of patients, at about 7 days. CONCLUSION: For a PET/CT study, an interval of 10 days after G-CSF administration is recommended to minimize the influence of G-CSF on the bone marrow when evaluating treatment response in patients with non-Hodgkin's lymphoma.