Phase I evaluation of CycloSam® (Sm-153-DOTMP) bone seeking radiopharmaceutical in dogs with spontaneous appendicular osteosarcoma.

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.

Laminated holmium-166-containing electrospun bandages for use against skin cancer.

The number of non-melanoma skin cancer (NMSC) cases in the US will increase significantly over the next decade due to a rise in UV exposure. One of the treatment methods used to remove NMSC lesions is radiation therapy. The two types of radiation therapy used in the clinic are external beam therapy and brachytherapy. However, both require specialized on-site instrumentation and for patients to remain immobile. In this work, we studied an alternative radiation therapy - one that does not require expensive on-site equipment and would allow for enhanced patient mobility and, thus, comfort. We prepared sealed source, nylon-laminated holmium-166-containing radiotherapeutic bandages and used them in C3H/HeN mice with murine SCCVII tumor grafts. Overall, tumor sizes were smallest when treated with therapeutically relevant radiation doses via radiotherapeutic bandages (compared to controls), and no histological evidence of toxicity to tissues was observed. Thus, our optimized radiotherapeutic bandage offers a flexible approach to treating NMSC.

Dosimetric implications of the potential radionuclidic impurities in 153Sm-DOTMP.

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.

RADAR Guide: Standard Methods for Calculating Radiation Doses for Radiopharmaceuticals, Part 2-Data Analysis and Dosimetry.

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.

RADAR Guide: Standard Methods for Calculating Radiation Doses for Radiopharmaceuticals, Part 1-Collection of Data for Radiopharmaceutical Dosimetry.

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.

High-specific-activity iodine 131 metaiodobenzylguanidine for the treatment of metastatic pheochromocytoma or paraganglioma: a novel therapy for an orphan disease.

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.

Radiation Safety Considerations in the Treatment of Canine Skeletal Conditions Using 153Sm, 90Y, and 117mSn.

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: Sm-1,4,7,10-tetraazacylcododecanetetramethylenephosphonic acid, which is a bone-seeking radiopharmaceutical; unencapsulated Y permanent interstitial implants, which are sometimes called "liquid brachytherapy"; and Sn radiosynoviorthesis, which is also called radiosynovectomy. External exposure rate readings of the Sm and Sn treatments, and Monte Carlo simulations of Sn 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 Y interstitial implant or for a month following Sn radiosynoviorthesis. No such avoidance is necessary after treatment with Sm-1,4,7,10-tetraazacylcododecanetetramethylenephosphonic acid.

Prediction of 1p/19q Codeletion in Diffuse Glioma Patients Using Pre-operative Multiparametric Magnetic Resonance Imaging.

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.

A measurement of the attenuation of radiation from F-18 by a PET/MR scanner.

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.

HU deviation in lung and bone tissues: Characterization and a corrective strategy.

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.

The influence of non-rigid anatomy and patient positioning on endoscopy-CT image registration in the head and neck.

PURPOSE: To 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. METHODS: Radiotherapy 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. RESULTS: Average 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). CONCLUSIONS: Inconsistencies 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.

The feasibility of endoscopy-CT image registration in the head and neck without prospective endoscope tracking.

PURPOSE: Endoscopic examinations are frequently-used procedures for patients with head and neck cancer undergoing radiotherapy, but radiation treatment plans are created on computed tomography (CT) scans. Image registration between endoscopic video and CT could be used to improve treatment planning and analysis of radiation-related normal tissue toxicity. The purpose of this study was to explore the feasibility of endoscopy-CT image registration without prospective physical tracking of the endoscope during the examination. METHODS: A novel registration technique called Location Search was developed. This technique uses physical constraints on the endoscope's view direction to search for the virtual endoscope coordinates that maximize the similarity between the endoscopic video frame and the virtual endoscopic image. Its performance was tested on phantom and patient images and compared to an established registration technique, Frame-To-Frame Tracking. RESULTS: In phantoms, Location Search had average registration errors of 0.55 ± 0.60 cm for point measurements and 0.29 ± 0.15 cm for object surface measurements. Frame-To-Frame Tracking achieved similar results on some frames, but it failed on others due to the virtual endoscope becoming lost. This weakness was more pronounced in patients, where Frame-To-Frame tracking could not make it through the nasal cavity. On successful patient video frames, Location Search was able to find endoscope positions with an average distance of 0.98 ± 0.53 cm away from the ground truth positions. However, it failed on many frames due to false similarity matches caused by anatomical structural differences between the endoscopic video and the virtual endoscopic images. CONCLUSIONS: Endoscopy-CT image registration without prospective physical tracking of the endoscope is possible, but more development is required to achieve an accuracy suitable for clinical translation.

Skeletal Tumor Burden on Baseline 18F-Fluoride PET/CT Predicts Bone Marrow Failure After 223Ra Therapy.

PURPOSE: Determine if skeletal tumor burden on 18F-fluoride PET/CT (fluoride PET/CT) predicts the risk of bone marrow failure (BMF) after 223Ra dichloride therapy (223Ra). METHODS: Forty-one metastatic prostate cancer patients (43-89 years old; mean, 71 ± 9 years.) underwent fluoride PET/CT prior to 223Ra. Bone marrow failure was the primary end point and was defined as (1) development of hematologic toxicity (World Health Organization grade 3 or 4) associated with no recovery after 6 weeks or (2) death due to BMF after the last 223Ra dose. Bone marrow failure was correlated to fluoride PET/CT skeletal tumor burden (TLF10 [total lesion on fluoride PET/CT with SUVmax of 10 or greater]), use of chemotherapy, serum hemoglobin concentration, serum ALP, and serum prostate-specific antigen. RESULTS: The number of 223Ra cycles ranged from 2 to 6 (mean, 5). Of the 41 patients, 16 developed BMF (G3 = 12; G4 = 4). A significantly increased risk of developing BMF was observed in patients with TLF10 of 12,000 or greater (hazard ratio [HR], 11.09; P < 0.0001), hemoglobin of less than 10 g/dL (HR, 7.35; P = 0.0002), and AP > 146 UI/L (HR, 4.52; P = 0.0100). Neither concomitant (HR, 0.91; P = 0.88) nor subsequent use of chemotherapy (HR, 0.14; P = 0.84) increased the risk of BMF, nor was prostate-specific antigen greater than 10 µg/L (HR, 0.90; P = 0.86). Moreover, in a multivariable analysis, TLF10 was the only independent predictor of BMF (HR, 6.66; P = 0.0237). CONCLUSIONS: 223Ra was beneficial and reduced the risk of death even in patients with a high skeletal tumor burden. Fluoride PET/CT is able to determine which patients will benefit from 223Ra and which will develop BMF.

Dosimetry of a (90)Y-hydroxide liquid brachytherapy treatment approach to canine osteosarcoma using PET/CT.

A new treatment strategy based on direct injections of (90)Y-hydroxide into the tumor bed in dogs with osteosarcoma was studied. Direct injections of the radiopharmaceutical into the tumor bed were made according to a pretreatment plan established using (18)F-FDG images. Using a special drill, cannulas were inserted going through tissue, tumor and bone. Using these cannulas, direct injections of the radiopharmaceutical were made. The in vivo biodistribution of (90)Y-hydroxide and the anatomical tumor bed were imaged using a time-of-flight (TOF) PET/CT scanner. The material properties of the tissues were estimated from corresponding CT numbers using an electron-density calibration. Radiation absorbed dose estimates were calculated using Monte Carlo methods where the biodistribution of the pharmaceutical from PET images was sampled using a collapsing 3-D rejection technique. Dose distributions in the tumor bed and surrounding tissues were calculated, showing significant heterogeneity with multiple hot spots at injection sites. Dose volume histograms showed that approximately 33.9% of bone and tumor and 70.2% of bone marrow and trabecular bone received an absorbed dose over 200Gy; approximately 3.2% of bone and tumor and 31.0% of bone marrow and trabecular bone received a total dose of over 1000Gy.

A preclinical investigation of the saturation and dosimetry of 153Sm-DOTMP as a bone-seeking radiopharmaceutical.

INTRODUCTION: The therapeutic potential of the bone-seeking radiopharmaceutical 153Sm-labeled 1,4,7,10-tetraazacyclododecanetetramethylenephosphonic acid (153Sm-DOTMP) was assessed by measuring its dosage-dependent skeletal uptake at two chelant-to-metal ratios and its source organ residence times at a chelant-to-metal ratio of 1.5:1. A similar agent, 153Sm-labeled ethylenediaminetetramethylenephosphonic acid (153Sm-EDTMP), has been reported to exhibit dosage-limiting skeletal saturation. METHODS: Sm-DOTMP was prepared with tracer activity of 153Sm and sufficient stable, unenriched Sm to simulate different activities. Cohorts of seven 280-g Sprague-Dawley rats were administered the equivalent of 296, 592, 888, 1184 and 1480 MBq (8, 16, 24, 32 and 40 mCi) at a fixed chelant-to-metal ratio of 1.5:1 and euthanized 3 h after administration. Cohorts of three 128-g Sprague-Dawley rats were administered equivalent dosages of 10.4, 592 and 888 (0.28, 16 and 32 mCi) at a fixed chelant-to-metal ratio of 270:1 and euthanized 2 h after administration. A simulated activity of 1480 MBq (40 mCi) at a chelant-to-metal ratio of 1.5:1 was administered to cohorts of seven rats that were euthanized at 2, 4, 24 or 48 h postadministration. The heart, lungs, liver, spleen, kidneys, small intestine, large intestine, urinary bladder, muscle and a femur were excised, weighed and counted. The data were analyzed to determine skeletal uptake and source organ residence times. RESULTS: No statistically significant skeletal saturation was observed up to human-equivalent dosages of 370 GBq (10 Ci) at a chelant-to-metal ratio of 1.5:1, but the skeletal uptake dropped by 40% over the range of dosages at a chelant-to-metal ratio of 270:1. At a chelant-to-metal ratio of 1.5:1, the preferred ratio, the skeletal uptake fraction in rats was 0.408 (95% confidence interval 0.396-0.419) with an effective half-life of 47.3 h (95% confidence interval 42.3-53.7; the physical half-life of 153Sm is 46.3 h). Extrapolating to an adult human model, 52.9 GBq (1.43 Ci) of 153Sm-DOTMP would deliver 40 Gy to the red marrow. CONCLUSION: 153Sm-DOTMP has dosimetry equivalent to that of 153Sm-EDTMP at low dosages, yet with no skeletal saturation at higher administered activities.

Pharmacokinetics, metabolism, biodistribution, radiation dosimetry, and toxicology of (18)F-fluoroacetate ((18)F-FACE) in non-human primates.

INTRODUCTION: To facilitate the clinical translation of (18)F-fluoroacetate ((18)F-FACE), the pharmacokinetics, biodistribution, radiolabeled metabolites, radiation dosimetry, and pharmacological safety of diagnostic doses of (18)F-FACE were determined in non-human primates. METHODS: (18)F-FACE was synthesized using a custom-built automated synthesis module. Six rhesus monkeys (three of each sex) were injected intravenously with (18)F-FACE (165.4 ± 28.5 MBq), followed by dynamic positron emission tomography (PET) imaging of the thoracoabdominal area during 0-30 min post-injection and static whole-body PET imaging at 40, 100, and 170 min. Serial blood samples and a urine sample were obtained from each animal to determine the time course of (18)F-FACE and its radiolabeled metabolites. Electrocardiograms and hematology analyses were obtained to evaluate the acute and delayed toxicity of diagnostic dosages of (18)F-FACE. The time-integrated activity coefficients for individual source organs and the whole body after administration of (18)F-FACE were obtained using quantitative analyses of dynamic and static PET images and were extrapolated to humans. RESULTS: The blood clearance of (18)F-FACE exhibited bi-exponential kinetics with half-times of 4 and 250 min for the fast and slow phases, respectively. A rapid accumulation of (18)F-FACE-derived radioactivity was observed in the liver and kidneys, followed by clearance of the radioactivity into the intestine and the urinary bladder. Radio-HPLC analyses of blood and urine samples demonstrated that (18)F-fluoride was the only detectable radiolabeled metabolite at the level of less than 9% of total radioactivity in blood at 180 min after the (18)F-FACE injection. The uptake of free (18)F-fluoride in the bones was insignificant during the course of the imaging studies. No significant changes in ECG, CBC, liver enzymes, or renal function were observed. The estimated effective dose for an adult human is 3.90-7.81 mSv from the administration of 185-370 MBq of (18)F-FACE. CONCLUSIONS: The effective dose and individual organ radiation absorbed doses from administration of a diagnostic dosage of (18)F-FACE are acceptable. From a pharmacologic perspective, diagnostic dosages of (18)F-FACE are non-toxic in primates and, therefore, could be safely administered to human patients for PET imaging.

Whole-body biodistribution kinetics, metabolism, and radiation dosimetry estimates of 18F-PEG6-IPQA in nonhuman primates.

UNLABELLED: We recently developed the radiotracer 4-[(3-iodophenyl)amino]-7-(2-[2-{2-(2-[2-{2-((18)F-fluoroethoxy)-ethoxy}-ethoxy]-ethoxy)-ethoxy}-ethoxy]-quinazoline-6-yl-acrylamide) ((18)F-PEG(6)-IPQA) for noninvasive detection of active mutant epidermal growth factor receptor kinase-expressing non-small cell lung cancer xenografts in rodents. In this study, we determined the pharmacokinetics, biodistribution, metabolism, and radiation dosimetry of (18)F-PEG(6)-IPQA in nonhuman primates. METHODS: Six rhesus macaques were injected intravenously with 141 ± 59.2 MBq of (18)F-PEG(6)-IPQA, and dynamic PET/CT images covering the thoracoabdominal area were acquired for 30 min, followed by whole-body static images at 60, 90, 120, and 180 min. Blood samples were obtained from each animal at several time points after radiotracer administration. Radiolabeled metabolites in blood and urine were analyzed using high-performance liquid chromatography. The (18)F-PEG(6)-IPQA pharmacokinetic and radiation dosimetry estimates were determined using volume-of-interest analysis of PET/CT image datasets and blood and urine time-activity data. RESULTS: (18)F-PEG(6)-IPQA exhibited rapid redistribution and was excreted via the hepatobiliary and urinary systems. (18)F-PEG(6) was the major radioactive metabolite. The critical organ was the gallbladder, with an average radiation-absorbed dose of 0.394 mSv/MBq. The other key organs with high radiation doses were the kidneys (0.0830 mSv/MBq), upper large intestine wall (0.0267 mSv/MBq), small intestine (0.0816 mSv/MBq), and liver (0.0429 mSv/MBq). Lung tissue exhibited low uptake of (18)F-PEG(6)-IPQA due to the low affinity of this radiotracer to wild-type epidermal growth factor receptor kinase. The effective dose was 0.0165 mSv/MBq. No evidence of acute cardiotoxicity or of acute or delayed systemic toxicity was observed. On the basis of our estimates, diagnostic dosages of (18)F-PEG(6)-IPQA up to 128 MBq (3.47 mCi) per injection should be safe for administration in the initial cohort of human patients in phase I clinical PET studies. CONCLUSION: The whole-body and individual organ radiation dosimetry characteristics and pharmacologic safety of diagnostic dosages of (18)F-PEG(6)-IPQA in nonhuman primates indicate that this radiotracer should be acceptable for PET/CT studies in human patients.

Hybrid Modality Fusion of Planar Scintigrams and CT Topograms to Localize Sentinel Lymph Nodes in Breast Lymphoscintigraphy: Technical Description and Phantom Studies.

Lymphoscintigraphy is a nuclear medicine procedure that is used to detect sentinel lymph nodes (SLNs). This project sought to investigate fusion of planar scintigrams with CT topograms as a means of improving the anatomic reference for the SLN localization. Heretofore, the most common lymphoscintigraphy localization method has been backlighting with a (57)Co sheet source. Currently, the most precise method of localization through hybrid SPECT/CT increases the patient absorbed dose by a factor of 34 to 585 (depending on the specific CT technique factors) over the conventional (57)Co backlighting. The new approach described herein also uses a SPECT/CT scanner, which provides mechanically aligned planar scintigram and CT topogram data sets, but only increases the dose by a factor of two over that from (57)Co backlighting. Planar nuclear medicine image fusion with CT topograms has been proven feasible and offers a clinically suitable compromise between improved anatomic details and minimally increased radiation dose.

Acquisition parameters for oncologic imaging with a new SPECT/multislice CT scanner.

INTRODUCTION: Single photon emission computed tomography/computed tomography (SPECT/CT) delivers in a single imaging modality the functional-metabolic information from the SPECT image, combined with the detailed anatomical information from a diagnostic quality CT scanner. METHOD: In this review, we provide the details for the acquisition, processing, and display of the SPECT, as well as the CT, and the fused SPECT/CT images, with one of the newest devices that combines a dual-headed gamma camera with a multislice CT scanner. Also, we go over the performance characteristics, including the planning and installation requirements for this type of scanners. In addition, we describe what are the current and feasible near-future applications of this new and exciting hybrid imaging modality. DISCUSSION: The ability to combine an optimized state-of-the-art SPECT image, with resolutions down to 5 mm, with a diagnostic quality CT image-using slices as thin as 1.25 mm-provides a diagnostic advantage that potentially can deliver a more convenient and faster diagnosis, with clinical implications in a significant percentage of patients. This imaging technique has been investigated in a wide range of studies for the oncologic patient, including but not limited to bone scintigraphy, (111)In-pentetreotide scintigraphy, lymphoscintigraphy, (67)Ga and labeled leukocyte infection imaging, (131)I-metaiodobenzylguanidine, parathyroid scintigraphy, (131)I diagnostic scintigraphy, and (111)In ProstaScint, and for planning of radionuclide therapy. CONCLUSION: Therefore, this evolving and exciting imaging modality will continue to grow and define its place as an integral part of the evaluation of the cancer patient.

Pilot study of targeted skeletal radiation therapy for bone-only metastatic breast cancer.

PURPOSE: Bone-targeted radiation therapy is an attractive strategy for addressing bone disease with minimal systemic toxicity. This pilot study was designed to determine the safety and efficacy of (166)Holmium (Ho)-DOTMP for irradiating malignant cells and adjacent marrow in women with bone-only metastatic breast cancer. PATIENTS AND METHODS: Subjects included 6 women aged < or = 65 years with breast cancer and bone-only metastases at M. D. Anderson Cancer Center. The activity of (166)Ho-DOTMP was calculated to deliver a therapeutic absorbed dose of 22 Gy (n = 3) or 28 Gy (n = 3) to the marrow. Treatment was followed by autologous stem cell transplantation to circumvent the anticipated myelosuppresion. Median follow-up time was 40 months. RESULTS: All subjects showed prompt hematologic recovery. No patient experienced grade 3/4 acute toxicity aside from myelosuppression. Two patients developed hemorrhagic cystitis 2 years after therapy. One patient developed myelodysplastic syndrome but was found to have had pre-existing trisomy 8. Two patients remained progression free without evidence of disease for more than 6 years. Five women experienced disease relapse (4 at extraosseous sites) and died of progressive disease. Median time to progression was 10.4 months. CONCLUSION: The approach of bone-targeted radiation therapy with (166)Ho-DOTMP had an acceptable toxicity profile, and sustained complete response was obtained in 2 of 6 patients. We are conducting a phase II study to evaluate the efficacy of targeted skeletal radiation therapy for treating bone-only metastases.