153 Sm-DOTMP (CycloSam® ) is a newly-patented radiopharmaceutical for bone tumor treatment. DOTMP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonate) is a macrocyclic chelating agent with superior binding properties to 153 Sm when compared with EDTMP (Quadramet™, used for palliative treatment of bone cancer). CycloSam® was administered at 1 mCi/kg (37 MBq/kg) in a prospective pilot study to seven dogs with bone cancer resulting in no myelosuppression. Then, 13 dogs were enrolled in a prospective clinical trial study using traditional 3+3 dose escalation and starting at 1.5 mCi/kg. Baseline evaluation included hematologic and biochemical testing, diagnosis confirmation, thoracic and limb radiographs, technetium-99 m-HDP bone scintigraphy, and 18 F-FDG PET scan (SUVmax). Toxicity (primary endpoint) was assessed through weekly blood counts and adverse events. Dogs received 1.5 mCi/kg (n = 4), 1.75 mCi/kg (n = 6), and 2 mCi/kg (n = 3) of 153 Sm-DOTMP. Dose-limiting neutropenia and thrombocytopenia were seen at 2 mCi/kg. No dose-limiting nonhematologic toxicities occurred. Efficacy (secondary endpoint) was assessed by objective lameness measurement (body-mounted inertial sensors), owner quality-of-life (QoL) questionnaire, and repeat PET scan. Objective lameness measurement improved in four dogs (53%-60% decrease) was equivocal in three dogs, and worsened in four dogs (66%-115% increase); two dogs were not evaluable. Repeat 18 F-FDG PET scan results varied and change in lameness did not consistently correlate with SUVmax changes. QoL score worsened (n = 5) or was improved/stable (n = 7). Carboplatin chemotherapy (300 mg/m2 IV every 3 weeks ×4) started 4 weeks after 153 Sm-DOTMP injection. No dog died of chemotherapy-related complications. All dogs completed study monitoring. The recommended dose for CycloSam® in dogs is 1.75 mCi/kg, which resulted in some pain control with minimal toxicity and was safely combined with chemotherapy.

Thehuman internal dosimetry of the radionuclidic impurities of samarium-153 in a new bone-seeking radiopharmaceutical, 153Sm-1,4,7,10tetraazacyclododecanetetramethylenephosponic acid (153Sm-DOTMP), has been estimated from preclinical data. The effective dose from the impurities in lower-specific-activity 153Sm is less than 17% of the effective dose from pure Sm-153. It has a background-equivalent radiation time for a dosage of 37 MBq/kg of less than one-half year.

This paper presents standardized methods for collecting data to be used in performing dose calculations for radiopharmaceuticals. Various steps in the process are outlined, with some specific examples given. This document can be used as a template for designing and executing kinetic studies for calculating radiation dose estimates, from animal or human data.

This paper presents standardized methods for performing dose calculations for radiopharmaceuticals. Various steps in the process are outlined, with some specific examples given. Special models for calculating time-activity integrals (urinary bladder, intestines) are also reviewed. This article can be used as a template for designing and executing kinetic studies for calculating radiation dose estimates from animal or human data.

Abstract The treatment of pets, service animals, and pre-clinical research subjects with radionuclides raises concern for the safety of the people who interact with the animals after their treatment. Three treatments of skeletal conditions in dogs are considered in this study: 153Sm-1,4,7,10-tetraazacylcododecanetetramethylenephosphonic acid, which is a bone-seeking radiopharmaceutical; unencapsulated 90Y permanent interstitial implants, which are sometimes called “liquid brachytherapy”; and 117mSn radiosynoviorthesis, which is also called radiosynovectomy. External exposure rate readings of the 153Sm and 117mSn treatments, and Monte Carlo simulations of 117mSn at a distance of 1 m and of all three in direct contact with tissue were analyzed for doses. Dogs that have received any of these treatments using typically administered activities may be released from radiation safety isolation immediately after treatment from the standpoint of external exposure. People should avoid prolonged close proximity, such as sleeping with a treated dog, for three weeks following an 90Y interstitial implant or for a month following 117mSn radiosynoviorthesis. No such avoidance is necessary after treatment with 153Sm-1,4,7,10-tetraazacylcododecanetetramethylenephosphonic acid.

PURPOSE OF REVIEW:Pheochromocytomas and paragangliomas represent less than 1% of all endocrine tumors. Approximately 15-20% of these tumors are malignant. The definition of malignancy relies on the presence of metastasis. Metastatic pheochromocytomas and paragangliomas are usually advanced, incurable tumors with limited therapeutic options. About 50-60% of these tumors express the noradrenaline transporter in their cell membranes. Recently, the United States Food and Drug Administration approved high-specific-activity iodine 131 metaiodobenzylguanidine (HSA-I-131-MIBG) for the treatment of metastatic pheochromocytomas and paragangliomas that express the noradrenaline transporter. This review reports the benefits and toxicity of HSA-I-131-MIBG, its physical and dosimetric aspects, and radiation safety precautions, as well as its potential therapeutic value for other malignancies (neuroblastoma, gastroenteropancreatic neuroendocrine tumors, and medullary thyroid carcinoma).RECENT FINDINGS:A phase 2 clinical trial with HSA-I-131-MIBG reported an impressive clinical benefit rate, acceptable toxicity and long-term benefits.SUMMARY:HSA-I-131-MIBG is an effective medication for metastatic pheochromocytomas and paragangliomas that express the noradrenaline transporter.

This study compared the predictive power and robustness of texture, topological, and convolutional neural network (CNN) based image features for measuring tumors in MRI. These features were used to predict 1p/19q codeletion in the MICCAI BRATS 2017 challenge dataset. Topological data analysis (TDA) based on persistent homology had predictive performance as good as or better than texture-based features and was also less susceptible to image-based perturbations. Features from a pre-trained convolutional neural network had similar predictive performances and robustness as TDA, but also performed better using an alternative classification algorithm, k-top scoring pairs. Feature robustness can be used as a filtering technique without greatly impacting model performance and can also be used to evaluate model stability.

The attenuation of 511 keV photons by the structure of a PET/MR scanner was measured prior to energizing the magnet. The exposure rate from a source of fluorine-18 was measured in air and, with the source placed at the isocenter of the instrument, at various points outside of the scanner. In an arc from 45 to 135 degrees relative to the long axis of the scanner and at a distance of 1.5 m from the isocenter, the attenuation by the scanner is at least 5.6 half-value layers from the MR component alone and at least 6.6 half-value layers with the PET insert installed. This information could inform better design of the radiation shielding for PET/MR scanners.

Tissue-classification-based attenuation correction strategies have been previously proposed to correct for bone attenuation in PET/MR imaging and simulated using computed tomography. However, the complication of voxel averaging uniquely associated with bone has not been considered explicitly in the past. This study investigated the effect of voxel averaging between bone and soft tissue in attenuation images and determined how accurately bone must be detected in MR images in order to perform acceptable attenuation correction of PET data by using CT-simulated attenuation correction. We found out that treating bone as soft tissue caused a mean quantification difference of -9.9% ± 5.5% in all 119 bone lesions. There were no significant differences between lesions in the pelvis and the vertebrae. The nominal difference in lesions in the ribs was significantly lower, likely due to the spatial misregistration between the emission and attenuation images. Interestingly, a non-monotonic relationship between the bone imaging ability and the absolute PET quantification accuracy was observed, with the minimal quantification difference achieved at a BVF around 40% for skull lesions (2.6% ± 2.1%), and 30% for non-skull lesions (1.4% ± 1.1%) and all lesions (1.5% ± 1.3%). This study established that a bone classification sensitivity of approximately 30% BVF is required in order for MR-based attenuation correction methods to achieve optimal quantification in whole-body PET/MR studies. For this purpose, higher bone imaging ability of MR may not be necessary.

Introduction: Radiosynoviorthesis (a.k.a. radiosynovectomy) treats arthritis by the intraarticular injection of a radioactive colloid. The radionuclides that are most often used are Y90 for large joints, Re-186 for medium-sized joints and Er-169 for small joints, along with P32 for treating hemophilic arthropathy. An ongoing trial of a novel colloid of Sn-117m, which emits therapeutic conversion electrons (~140 keV, 112%; range ~300 um), is producing very encouraging results in the treatment of arthritic canine elbow joints. These are comparable in size to some human joints. The 14-day physical half-life of Sn-117m allows time for phagocytosis and migration of the radioactive particles deeper into the tissue. It is thus conceivable that Sn-117m could treat larger joints with thicker synovia while still sparing the cartilage and bone. This study simulated moving distributions of the radionuclides in order to estimate the radiation absorbed dose in the structures of a treated joint.

INTRODUCTION:In the era of precision medicine, quantitative applications of x-ray Computed Tomography (CT) are on the rise. These require accurate measurement of the CT number, also known as the Hounsfield Unit. In this study, we evaluated the effect of patient attenuation-induced beam hardening of the x-ray spectrum on the accuracy of the HU values and a strategy to correct for the resulting deviations in the measured HU values.MATERIALS AND METHODS:A CIRS electron density phantom was scanned on a Siemens Biograph mCT Flow CT scanner and a GE Discovery 710 CT scanner using standard techniques that are employed in the clinic to assess the HU deviation caused by beam hardening in different tissue types. In addition, an anthropomorphic ATOM adult male upper torso phantom was scanned on the GE Discovery 710 scanner. Various amounts of Superflab bolus material were wrapped around the phantoms to simulate different patient sizes. The mean HU values that were measured in the phantoms were evaluated as a function of the water-equivalent area (Aw ), a parameter that is described in the report of AAPM Task Group 220. A strategy by which to correct the HU values was developed and tested. The variation in the HU values in the anthropomorphic ATOM phantom under different simulated body sizes, both before and after correction, were compared, with a focus on the lung and bone tissues.RESULTS:Significant HU deviations that depended on the simulated patient size were observed. A positive correlation between HU and Aw was observed for tissue types that have an HU of less than zero, while a negative correlation was observed for tissue types with HU values that are greater than zero. The magnitude of the difference increases as the underlying attenuation property deviates further away from that of water. In the electron density phantom study, the maximum observed HU differences between the measured and reference values in the cortical bone and lung materials were 426 and 94 HU, respectively. In the anthropomorphic phantom study, the HU difference was as much as -136.7 ± 8.2 HU (or -7.6% ± 0.5% of the attenuation coefficient, AC) in the spine region, and up to 37.6 ± 1.6 HU (or 17.3% ± 0.8% of AC) in the lung region between scenarios that simulated normal and obese patients. Our HU correction method reduced the HU deviations to 8.5 ± 9.1 HU (or 0.5% ± 0.5%) for bone and to -6.4 ± 1.7 HU (or -3.0% ± 0.8%) for lung. The HU differences in the soft tissue materials before and after the correction were insignificant. Visual improvement of the tissue contrast was also achieved in the data of the simulated obese patient.CONCLUSIONS:The effect of a patient's size on the HU values of lung and bone tissues can be significant. The accuracy of those HU values was substantially improved by the correction method that was developed for and employed in this study.

474 Objectives: Tin-117m is a promising radionuclide for the treatment of arthritis. Currently, radiosynoviorthesis employs Y-90 or P-32 for large joints, Re-186 for medium-sized joints and Er-169 for small joints based upon the energies and hence the ranges of their emitted beta particles. This study sought to demonstrate the utility of a Sn-117m colloid in the treatment of various sized joints. While the 300 µm range of its conversion electrons makes it intrinsically suitable for small joints, its relatively long 14-day half-life might allow the colloidal particles to be transported by macrophages deeper into the synovial tissues and thereby effectively treat larger joints. Methods: Static and dynamic models of Sn-117m radiosynoviorthesis were developed using the Geant4 Application for Emission Tomography (GATE) Monte-Carlo software. The geometry of a synovial joint in the simulation was adopted from the planar layered model in the dissertation of LS Johnson. All five radionuclides were simulated in both static and dynamic situations. The 6 µm colloidal particles labeled with one of the radionuclides were initially arrayed in a rectilinear grid with a center-to-center spacing of 0.1 mm in a plane at the interface between the joint capsule and the intima. In the dynamic model, the particles then moved perpendicular to the planes of the joint layers with a uniform distribution of velocities. Their maximum speed of 8.58×10-8 mm/s was estimated from an analysis of post-mortem autoradiographs of the elbows of treated dogs. The dose as a function of depth in the model was plotted for both the static and dynamic models for all five radionuclides. Results: The activity that was required to deliver the same peak dose as that from 1 MBq/cm2 of Sn-117m was 7.68 MBq/cm2 of Y-90, 2.07 MBq/cm2 of Er-169, 4.74 MBq/cm2 of Re-186, and 1.41 MBq/cm2 of P-32 in the static simulation and 5.30 MBq/cm2 of Y-90, 1.81 MBq/cm2 of Er-169, 3.38 MBq/cm2 of Re-186, and 1.16 MBq/cm2 of P-32 in the dynamic simulation. The shapes of the dose distribution curves were very similar for Sn-117m and Er-169. Tin-117m and Re-186 can each deliver 100 Gy as deeply as 0.5 mm into the synovial tissue with dosages of 4.19 MBq/cm2 and 1.46 MBq/cm2 respectively. Conclusions: Tin-117m could be substituted for Re-186 in the treatment of medium-sized joints as well as for Er-169 in the treatment of small joints. Research Support: This work was supported by an unrestricted grant from Serene, LLC and by the Center for the Integration of STEM Education & Research (CISER) Undergraduate Research Program at Texas Tech University.

477 Objectives: Radiosynoviorthesis using a tin-117m colloid is proving to be an effective treatment of osteoarthritis of the canine elbow. This study used new clinical measurements of external exposure and Monte Carlo simulations in order to develop guidelines for the release of treated animals from radiation safety isolation based upon the public dose limit of 1 mSv. Methods: Twelve adult dogs were treated with the Sn-117m colloid for Grade 3 osteoarthritis of the elbow. The nominal dosage of 1.75 mCi to an elbow of a 50 pound dog was adjusted by weight-based body surface area and capped at 3 mCi. Nine dogs were treated in both elbows and three were treated in just one. They weighed 73.8±16.4 [50-101] pounds and received 3.7±1.3 [1.6-5.6] mCi in all. The external exposure rate was measured using a Ludlum 9DP ionization meter laterally at distances of 5 cm and 1 m and cranially at a distance of 1 m as soon as the dogs awoke from sedation and again on the next day. These situations were simulated in a stylized fashion using the Gate Monte Carlo software. For release calculations, walking and playing with a dog were modeled as separation by 3 feet while feeding and petting a dog were modeled as separation by 1 foot. Results: The simulation of a point source in air gave a dose rate constant of 1.54×10-17 Gy-m2/Bq-s at a depth of 1 cm into water, which is mid-way between the extreme values calculated using the ANSI/ANS-6.1.1-1991 methodology. The simulation of two legs gave an attenuation of the dose from the far joint of 50%. Including this effect, the measured lateral dose rate at 1 m was 52% of the expected dose rate in air and the cranial dose rate was 37% of that expected in air, so for release calculations, an effective dose rate of 8.0×10-18 Gy-m2/Bq-s was used regardless of orientation. The measurements that were made immediately post-treatment and those from the next day did not differ significantly. The restrictions on an individual person’s interacting with dogs that were given the maximum dosage of this cohort or the nominal dosage for modeled exposure times while keeping the person’s total dose below 1 mSv are tabulated. After ten weeks (or five physical half-lives), more relaxed restrictions would typically allow a further dose of only 0.15 mSv or less. Conclusions: Dogs that have been treated with Sn-117m radiosynoviorthesis may be released from radiation safety isolation immediately after treatment with tolerable restrictions on human interactions.

PurposeTo assess the influence of non‐rigid anatomy and differences in patient positioning between CT acquisition and endoscopic examination on endoscopy‐CT image registration in the head and neck.MethodsRadiotherapy planning CTs and 31–35 daily treatment‐room CTs were acquired for nineteen patients. Diagnostic CTs were acquired for thirteen of the patients. The surfaces of the airways were segmented on all scans and triangular meshes were created to render virtual endoscopic images with a calibrated pinhole model of an endoscope. The virtual images were used to take projective measurements throughout the meshes, with reference measurements defined as those taken on the planning CTs and test measurements defined as those taken on the daily or diagnostic CTs. The influence of non‐rigid anatomy was quantified by 3D distance errors between reference and test measurements on the daily CTs, and the influence of patient positioning was quantified by 3D distance errors between reference and test measurements on the diagnostic CTs. The daily CT measurements were also used to investigate the influences of camera‐to‐surface distance, surface angle, and the interval of time between scans.ResultsAverage errors in the daily CTs were 0.36 ± 0.61 cm in the nasal cavity, 0.58 ± 0.83 cm in the naso‐ and oropharynx, and 0.47 ± 0.73 cm in the hypopharynx and larynx. Average errors in the diagnostic CTs in those regions were 0.52 ± 0.69 cm, 0.65 ± 0.84 cm, and 0.69 ± 0.90 cm, respectively. All CTs had errors heavily skewed towards 0, albeit with large outliers. Large camera‐to‐surface distances were found to increase the errors, but the angle at which the camera viewed the surface had no effect. The errors in the Day 1 and Day 15 CTs were found to be significantly smaller than those in the Day 30 CTs (P < 0.05).ConclusionsInconsistencies of patient positioning have a larger influence than non‐rigid anatomy on projective measurement errors. In general, these errors are largest when the camera is in the superior pharynx, where it sees large distances and a lot of muscle motion. The errors are larger when the interval of time between CT acquisitions is longer, which suggests that the interval of time between the CT acquisition and the endoscopic examination should be kept short. The median errors found in this study are comparable to acceptable levels of uncertainty in deformable CT registration. Large errors are possible even when image alignment is very good, indicating that projective measurements must be made carefully to avoid these outliers.