Sami Suilamo

Plasma Pharmacokinetics, Whole-Body Distribution, Metabolism, and Radiation Dosimetry of 68Ga Bombesin Antagonist BAY 86-7548 in Healthy Men

This first-in-human study investigated the safety, tolerability, metabolism, pharmacokinetics, biodistribution, and radiation dosimetry of 68Ga-bombesin antagonist 68Ga-DOTA-4-amino-1-carboxymethylpiperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (BAY 86-7548). Methods: Five healthy men underwent dynamic whole-body PET/CT after an intravenous injection of BAY 86-7548 (138 ± 5 MBq). Besides total radioactivity, plasma samples were analyzed by radio–high-performance liquid chromatography for metabolism of the tracer. Dosimetry was calculated using the OLINDA/EXM software. Results: Three radioactive plasma metabolites were detected. The proportion of unchanged BAY 86-7548 decreased from 92% ± 9% at 1 min after injection to 19% ± 2% at 65 min. The organs with the highest absorbed doses were the urinary bladder wall (0.62 mSv/MBq) and the pancreas (0.51 mSv/MBq). The mean effective dose was 0.051 mSv/MBq. BAY 86-7548 was well tolerated by all subjects. Conclusion: Intravenously injected BAY 86-7548 is safe, and rapid metabolism is demonstrated. A 150-MBq injection of BAY 86-7548 results in an effective dose of 7.7 mSv, which could be reduced to 5.7 mSv with frequent bladder voids.

Preclinical Evaluation of a Radioiodinated Fully Human Antibody for In Vivo Imaging of Vascular Adhesion Protein-1–Positive Vasculature in Inflammation

Vascular adhesion protein-1 (VAP-1) is an endothelial glycoprotein mediating leukocyte trafficking from blood to sites of inflammation. BTT-1023 is a fully human monoclonal anti-VAP-1 antibody developed to treat inflammatory diseases. In this study, we preclinically evaluated radioiodinated BTT-1023 for inflammation imaging. Methods: Rabbits were intravenously injected with radioiodinated BTT-1023. Distribution and pharmacokinetics were assessed by PET/CT up to 72 h after injection. Human radiation dose estimates for 124I-BTT-1023 were extrapolated. Additionally, rabbits with chemically induced synovitis were imaged with 123I-BTT-1023 SPECT/CT. Results: Radioiodinated BTT-1023 cleared rapidly from blood circulation and distributed to liver and thyroid. Inflamed joints were delineated by SPECT/CT. The estimated human effective dose due to 124I-BTT-1023 was 0.55 mSv/MBq, if blockage of thyroid uptake is assumed. Conclusion: The radioiodinated BTT-1023 was able to detect mild inflammation in vivo. Clinical 124I-BTT-1023 PET studies with injected radioactivity of 0.5–0.7 MBq/kg may be justified.

A dosimetric phantom study of dose accuracy and build-up effects using IMRT and RapidArc in stereotactic irradiation of lung tumours

Background and purposeStereotactic lung radiotherapy (SLRT) has emerged as a curative treatment for medically inoperable patients with early-stage non-small cell lung cancer (NSCLC) and the use of intensity-modulated radiotherapy (IMRT) and volumetric modulated arc treatments (VMAT) have been proposed as the best practical approaches for the delivery of SLRT. However, a large number of narrow field shapes are needed in the dose delivery of intensity-modulated techniques and the probability of underdosing the tumour periphery increases as the effective field size is decreased. The purpose of this study was to evaluate small lung tumour doses irradiated by intensity-modulated techniques to understand the risk for dose calculation errors in precision radiotherapy such as SLRT.Materials and methodsThe study was executed with two heterogeneous phantoms with targets of Ø1.5 and Ø4.0 cm. Dose distributions in the simulated tumours delivered by small sliding window apertures (SWAs), IMRT and RapidArc treatment plans were measured with radiochromic film. Calculation algorithms of pencil beam convolution (PBC) and anisotropic analytic algorithm (AAA) were used to calculate the corresponding dose distributions.ResultsPeripheral doses of the tumours were decreased as SWA decreased, which was not modelled by the calculation algorithms. The smallest SWA studied was 2 mm, which reduced the 90% isodose line width by 4.2 mm with the Ø4.0 cm tumour as compared to open field irradiation. PBC was not able to predict the dose accurately as the gamma evaluation failed to meet the criteria of ±3%/±1 mm on average in 61% of the defined volume with the smaller tumour. With AAA the corresponding value was 16%. The dosimetric inaccuracy of AAA was within ±3% with the optimized treatment plans of IMRT and RapidArc. The exception was the clinical RapidArc plan with dose overestimation of 4%.ConclusionsOverall, the peripheral doses of the simulated lung tumours were decreased by decreasing the SWA. To achieve adequate surface dose coverage to small lung tumours with a difference less than 1 mm in the isodose line radius between the open and modulated field, a larger than 6 mm SWA should be used in the dose delivery of SLRT.

Radiation Dosimetry and Biodistribution of the Hypoxia Tracer 18F-EF5 in Oncologic Patients

UNLABELLED The primary goals of this study were to determine the biodistribution and excretion of (18)F-EF5 in oncologic patients, to estimate the radiation-absorbed dose and to determine the safety of this drug. METHODS Sixteen patients with histologically confirmed malignancy received a mean intravenous infusion of 217  MBq (range 107-364  MBq) of (18)F-EF5. Over a 4-6-hour period, four to five serial positron emission tomography (PET) or PET/computed tomography (CT) scans were obtained. To calculate the radiation dosimetry estimates, volumes of interest were drawn over the source organs for each PET scan or on the CT for each PET/CT scan. Serial blood samples were obtained to measure (18)F-EF5 blood clearance. Bladder-wall dose was calculated based on urine activity measurements. RESULTS The urinary bladder received the largest radiation-absorbed dose, 0.12 ± 0.034 mSv/MBq (mean ± SD). The average effective dose equivalent and the effective dose of (18)F-EF5 were 0.021 ± 0.003 mSv/MBq and 0.018 ± 0.002 mSv/MBq, respectively. (18)F-EF5 was well tolerated in all subjects. CONCLUSIONS (18)F-EF5 was demonstrated to be safe for patients, and the radiation exposure is clinically acceptable. As with any radiotracer with primary excretion in the urine, the bladder-wall dose can be minimized by active hydration and frequent voiding.

Magnetic resonance-only simulation and dose calculation in external beam radiation therapy: a feasibility study for pelvic cancers

Abstract Background: The clinical feasibility of using pseudo-computed tomography (pCT) images derived from magnetic resonance (MR) images for external bean radiation therapy (EBRT) planning for prostate cancer patients has been well demonstrated. This paper investigates the feasibility of applying an MR-derived, pCT planning approach to additional types of cancer in the pelvis. Material and methods: Fifteen patients (five prostate cancer patients, five rectal cancer patients, and five gynecological cancer patients) receiving EBRT at Turku University Hospital (Turku, Finland) were included in the study. Images from an MRCAT (Magnetic Resonance for Calculating ATtenuation, Philips, Vantaa, Finland) pCT method were generated as a part of a clinical MR-simulation procedure. Dose calculation accuracy was assessed by comparing the pCT-based calculation with a CT-based calculation. In addition, the degree of geometric accuracy was studied. Results: The median relative difference of PTV mean dose between CT and pCT images was within 0.8% for all tumor types. When assessing the tumor site-specific accuracy, the median [range] relative dose differences to the PTV mean were 0.7 [−0.11;1.05]% for the prostate cases, 0.3 [−0.25;0.57]% for the rectal cases, and 0.09 [−0.69;0.25]% for the gynecological cancer cases. System-induced geometric distortion was measured to be less than 1 mm for all PTV volumes and the effect on the PTV median dose was less than 0.1%. Conclusions: According to the comparison, using pCT for clinical EBRT planning and dose calculation in the three investigated types of pelvic cancers is feasible. Further studies are required to demonstrate the applicability to a larger cohort of patients.

Dosimetric Comparison and Evaluation of 4 Stereotactic Body Radiotherapy Techniques for the Treatment of Prostate Cancer

Purpose: The aim of this study was to compare dosimetric characteristics, monitor unit, and delivery efficiency of 4 different stereotactic body radiotherapy techniques for the treatment of prostate cancer. Methods: This study included 8 patients with localized prostate cancer. Dosimetric assets of 4 delivery techniques for stereotactic body radiotherapy were evaluated: robotic CyberKnife, noncoplanar intensity-modulated radiotherapy, and 2 intensity-modulated arc therapy techniques (RapidArc and Elekta volumetric-modulated arc therapy). All the plans had equal treatment margins and a prescription dose of 35 Gy in 5 fractions. Results: Statistically significant differences were observed in homogeneity index and mean doses of bladder wall and penile bulb, all of which were highest with CyberKnife. No significant differences were observed in the mean doses of rectum, with values of 15.2 ± 2.6, 13.3 ± 2.6, 13.1 ± 2.8, and 13.8 ± 1.6 Gy with CyberKnife, RapidArc, volumetric-modulated arc therapy, and noncoplanar intensity-modulated radiotherapy, respectively. The highest dose conformity was realized with RapidArc. The dose coverage of the planning target volume was lowest with noncoplanar intensity-modulated radiotherapy. Treatment times and number of monitor units were largest with CyberKnife (on average 34.0 ± 5.0 minutes and 8704 ± 1449 monitor units) and least with intensity-modulated arc therapy techniques (on average 5.1 ± 1.1 minutes and 2270 ± 497 monitor units). Conclusion: Compared to CyberKnife, the RapidArc, volumetric-modulated arc therapy, and noncoplanar intensity-modulated radiotherapy produced treatment plans with similar dosimetric quality, with RapidArc achieving the highest dose conformity. Overall, the dosimetric differences between the studied techniques were marginal, and thus, the choice of the technique should rather focus on the delivery accuracies and dose delivery times.

Isocentric integration of intensity-modulated radiotherapy with electron fields improves field junction dose uniformity in postmastectomy radiotherapy

Abstract Background. In postmastectomy radiotherapy (PMRT), the dose coverage of the planning target volume (PTV) with additional margins, including the chest wall, supraclavicular, interpectoral, internal mammary and axillar level I–III lymph nodes, is often compromised. Electron fields may improve the medial dose coverage while maintaining organ at risk (OAR) doses at an acceptable level, but at the cost of hot and cold spots at the electron and photon field junction. To improve PMRT dose coverage and uniformity, an isocentric technique combining tangential intensity-modulated (IM)RT fields with one medial electron field was implemented. Material and methods. For 10 postmastectomy patients isocentric IMRT with electron plans were created and compared with a standard electron/photon mix and a standard tangent technique. PTV dose uniformity was evaluated based on the tolerance range (TR), i.e. the ratio of the standard deviation to the mean dose, a dice similarity coefficient (DSC) and the 90% isodose coverage and the hot spot volumes. OAR and contralateral breast doses were also recorded. Results. IMRT with electrons significantly improved the PTV dose homogeneity and conformity based on the TR and DSC values when compared with the standard electron/photon and tangent technique (p < 0.02). The 90% isodose coverage improved to 86% compared with 82% and 80% for the standard techniques (p < 0.02). Compared with the standard electron/photon mix, IMRT smoothed the dose gradient in the electron and photon field junction and the volumes receiving a dose of 110% or more were reduced by a third. For all three strategies, the OAR and contralateral breast doses were within clinically tolerable limits. Conclusion. Based on these results two-field IMRT combined with an electron field is a suitable strategy for PMRT.

Radiotherapy volume delineation using dynamic [(18)F]-FDG PET/CT imaging in patients with oropharyngeal cancer: a pilot study.

PurposeDelineation of gross tumour volume in 3D is a critical step in the radiotherapy (RT) treatment planning for oropharyngeal cancer (OPC). Static [18F]-FDG PET/CT imaging has been suggested as a method to improve the reproducibility of tumour delineation, but it suffers from low specificity. We undertook this pilot study in which dynamic features in time-activity curves (TACs) of [18F]-FDG PET/CT images were applied to help the discrimination of tumour from inflammation and adjacent normal tissue.MethodsFive patients with OPC underwent dynamic [18F]-FDG PET/CT imaging in treatment position. Voxel-by-voxel analysis was performed to evaluate seven dynamic features developed with the knowledge of differences in glucose metabolism in different tissue types and visual inspection of TACs. The Gaussian mixture model and K-means algorithms were used to evaluate the performance of the dynamic features in discriminating tumour voxels compared to the performance of standardized uptake values obtained from static imaging.ResultsSome dynamic features showed a trend towards discrimination of different metabolic areas but lack of consistency means that clinical application is not recommended based on these results alone.ConclusionsImpact of inflammatory tissue remains a problem for volume delineation in RT of OPC, but a simple dynamic imaging protocol proved practicable and enabled simple data analysis techniques that show promise for complementing the information in static uptake values.