Report on the PET/CT Image-Based Radiation Dosimetry of [18F]FDHT in Women, a Validated Imaging Agent with New Applications for Evaluation of Androgen Receptor Status in Women with Metastatic Breast Cancer.

In a prospective clinical trial, [18F]fluoro-5α-dihydrotestosterone ([18F]FDHT), the radiolabeled analog of the androgen dihydrotestosterone, was used as a PET/CT imaging agent for in vivo assessment of metastatic androgen receptor-positive breast cancer in postmenopausal women. To our knowledge, this article presents the first report of PET/CT image-based radiation dosimetry of [18F]FDHT in women. Methods: [18F]FDHT PET/CT imaging was performed on a cohort of 11 women at baseline before the start of therapy and at 2 additional time points during selective androgen receptor modulator (SARM) therapy for androgen receptor-positive breast cancer. Volumes of interest (VOIs) were placed over the whole body and within source organs seen on the PET/CT images, and the time-integrated activity coefficients of [18F]FDHT were derived. The time-integrated activity coefficients for the urinary bladder were calculated using the dynamic urinary bladder model in OLINDA/EXM software, with biologic half-life for urinary excretion derived from VOI measurements of the whole body in postvoid PET/CT images. The time-integrated activity coefficients for all other organs were calculated from VOI measurements in the organs and the physical half-life of 18F. Organ dose and effective dose calculations were then performed using MIRDcalc, version 1.1. Results: At baseline before SARM therapy, the effective dose for [18F]FDHT in women was calculated as 0.020 ± 0.0005 mSv/MBq, and the urinary bladder was the organ at risk, with an average absorbed dose of 0.074 ± 0.011 mGy/MBq. Statistically significant decreases in liver SUV or uptake of [18F]FDHT were found at the 2 additional time points on SARM therapy (linear mixed model, P < 0.05). Likewise, absorbed dose to the liver also decreased by a small but statistically significant amount at the 2 additional time points (linear mixed model, P < 0.05). Neighboring abdominal organs of the gallbladder wall, stomach, pancreas, and adrenals also showed statistically significant decreases in absorbed dose (linear mixed model, P < 0.05). The urinary bladder wall remained the organ at risk at all time points. Absorbed dose to the urinary bladder wall did not show statistically significant changes from baseline at any of the time points (linear mixed model, P ≥ 0.05). Effective dose also did not show statistically significant changes from baseline (linear mixed model, P ≥ 0.05). Conclusion: Effective dose for [18F]FDHT in women before SARM therapy was calculated as 0.020 ± 0.0005 mSv/MBq. The urinary bladder wall was the organ at risk, with an absorbed dose of 0.074 ± 0.011 mGy/MBq.

Guidelines on Setting Up Stations for Remote Viewing of Nuclear Medicine and Molecular Imaging Studies During COVID-19.

The current pandemic has created a situation where nuclear medicine practitioners and medical physicists read or process nuclear medicine images remotely from their home office. This article presents recommendations on the components and specifications when setting up a remote viewing station for nuclear medicine imaging.

On the impact of longitudinal breathing motion randomness for tomotherapy delivery.

The purpose of this study is to explain the unplanned longitudinal dose modulations that appear in helical tomotherapy (HT) dose distributions in the presence of irregular patient breathing. This explanation is developed by the use of longitudinal (1D) simulations of mock and surrogate data and tested with a fully 4D HT delivered plan. The 1D simulations use a typical mock breathing function which allows more flexibility to adjust various parameters. These simplified simulations are then made more realistic by using 100 surrogate waveforms all similarly scaled to produce longitudinal breathing displacements. The results include the observation that, with many waveforms used simultaneously, a voxel-by-voxel probability of a dose error from breathing is found to be proportional to the realistically random breathing amplitude relative to the beam width if the PTV is larger than the beam width and the breathing displacement amplitude. The 4D experimental test confirms that regular breathing will not result in these modulations because of the insensitivity to leaf motion for low-frequency dynamics such as breathing. These modulations mostly result from a varying average of the breathing displacements along the beam edge gradients. Regular breathing has no displacement variation over many breathing cycles. Some low-frequency interference is also possible in real situations. In the absence of more sophisticated motion management, methods that reduce the breathing amplitude or make the breathing very regular are indicated. However, for typical breathing patterns and magnitudes, motion management techniques may not be required with HT because typical breathing occurs mostly between fundamental HT treatment temporal and spatial scales. A movement beyond only discussing margins is encouraged for intensity modulated radiotherapy such that patient and machine motion interference will be minimized and beneficial averaging maximized. These results are found for homogeneous and longitudinal on-axis delivery for unplanned longitudinal dose modulations.

[(18)F]-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography of LAPC4-CR Castration-Resistant Prostate Cancer Xenograft Model in Soft Tissue Compartments.

Preclinical xenograft models have contributed to advancing our understanding of the molecular basis of prostate cancer and to the development of targeted therapy. However, traditional preclinical in vivo techniques using caliper measurements and survival analysis evaluate the macroscopic tumor behavior, whereas tissue sampling disrupts the microenvironment and cannot be used for longitudinal studies in the same animal. Herein, we present an in vivo study of [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) designed to evaluate the metabolism within the microenvironment of LAPC4-CR, a unique murine model of castration-resistant prostate cancer. Mice bearing LAPC4-CR subcutaneous tumors were administered [(18)F]-FDG via intravenous injection. After a 60-minute distribution phase, the mice were imaged on a PET/CT scanner with submillimeter resolution; and the fused PET/CT images were analyzed to evaluate tumor size, location, and metabolism across the cohort of mice. The xenograft tumors showed [(18)F]-FDG uptake that was independent of tumor size and was significantly greater than uptake in skeletal muscle and liver in mice (Wilcoxon signed-rank P values of .0002 and .0002, respectively). [(18)F]-FDG metabolism of the LAPC4-CR tumors was 2.1 ± 0.8 ID/cm(3)*wt, with tumor to muscle ratio of 7.4 ± 4.7 and tumor to liver background ratio of 6.7 ± 2.3. Noninvasive molecular imaging techniques such as PET/CT can be used to probe the microenvironment of tumors in vivo. This study showed that [(18)F]-FDG-PET/CT could be used to image and assess glucose metabolism of LAPC4-CR xenografts in vivo. Further work can investigate the use of PET/CT to quantify the metabolic response of LAPC4-CR to novel agents and combination therapies using soft tissue and possibly bone compartment xenograft models.

Copper-64-diacetyl-bis(N(4)-methylthiosemicarbazone) pharmacokinetics in FaDu xenograft tumors and correlation with microscopic markers of hypoxia.

PURPOSE: The behavior of copper-64-diacetyl-bis(N(4)-methylthiosemicarbazone) ((64)Cu-ATSM) in hypoxic tumors was examined through a combination of in vivo dynamic positron emission tomography (PET) and ex vivo autoradiographic and histologic evaluation using a xenograft model of head-and-neck squamous cell carcinoma. METHODS AND MATERIALS: (64)Cu-ATSM was administered during dynamic PET imaging, and temporal changes in (64)Cu-ATSM distribution within tumors were evaluated for at least 1 hour and up to 18 hours. Animals were sacrificed at either 1 hour (cohort A) or after 18 hours (cohort B) postinjection of radiotracer and autoradiography performed. Ex vivo analysis of microenvironment subregions was conducted by immunohistochemical staining for markers of hypoxia (pimonidazole hydrochloride) and blood flow (Hoechst-33342). RESULTS: Kinetic analysis revealed rapid uptake of radiotracer by tumors. The net influx (K(i)) constant was 12-fold that of muscle, whereas the distribution volume (V(d)) was 5-fold. PET images showed large tumor-to-muscle ratios, which continually increased over the entire 18-hour course of imaging. However, no spatial changes in (64)Cu-ATSM distribution occurred in PET imaging at 20 minutes postinjection. Microscopic intratumoral distribution of (64)Cu-ATSM and pimonidazole were not correlated at 1 hour or after 18 hours postinjection, nor was (64)Cu-ATSM and Hoechst-33342. CONCLUSIONS: The oxygen partial pressures at which (64)Cu-ATSM and pimonidazole are reduced and bound in cells are theorized to be distinct and separable. However, this study demonstrated that microscopic distributions of these tracers within tumors are independent. Researchers have shown (64)Cu-ATSM uptake to be specific to malignant expression, and this work has also demonstrated clear tumor targeting by the radiotracer.

PET imaging for the quantification of biologically heterogeneous tumours: measuring the effect of relative position on image-based quantification of dose-painting targets.

Quantitative imaging of tumours represents the foundation of customized therapies and adaptive patient care. As such, we have investigated the effect of patient positioning errors on the reproducibility of images of biologically heterogeneous tumours generated by a clinical PET/CT system. A commercial multi-slice PET/CT system was used to acquire 2D and 3D PET images of a phantom containing multiple spheres of known volumes and known radioactivity concentrations and suspended in an aqueous medium. The spheres served as surrogates for sub-tumour regions of biological heterogeneities with dimensions of 5-15 mm. Between image acquisitions, a motorized-arm was used to reposition the spheres in 1 mm intervals along either the radial or the axial direction. Images of the phantom were reconstructed using typical diagnostic reconstruction techniques, and these images were analysed to characterize and model the position-dependent changes in contrast recovery. A simulation study was also conducted to investigate the effect of patient position on the reproducibility of PET imaging of biologically heterogeneous head and neck (HN) tumours. For this simulation study, we calculated the changes in image intensity values that would occur with changes in the relative position of the patients at the time of imaging. PET images of two HN patients were used to simulate an imaging study that incorporated set-up errors that are typical for HN patients. One thousand randomized positioning errors were investigated for each patient. As a result of the phantom study, a position-dependent trend was identified for measurements of contrast recovery of small objects. The peak contrast recovery occurred at radial and axial positions that coincide with the centre of the image voxel. Conversely, the minimum contrast recovery occurred when the object was positioned at the edges of the image voxel. Changing the position of high contrast spheres by one-half the voxel dimension lead to errors in the measurement of contrast recovery values which were larger than 30%. However, the magnitudes of the errors were found to depend on the size of the sphere and method of image reconstruction. The error values from standard OSEM images of the 5 mm diameter sphere were 20-35%, and for the 10 mm diameter sphere were 5-10%. The position-dependent variation of contrast recovery can result in changes in spatial distribution within images of heterogeneous tumours. In experiments simulating random set-up errors during imaging of two HN patients, the expectation value of the correlation was approximately 1.0 for these tumours; however, Pearson correlation coefficient values as low as 0.8 were observed. Moreover, variations within the images can drastically change the delineation of biological target volumes. The errors in target delineation were more prominent in very heterogeneous tumours. As an example, in a pair of images with a correlation of 0.8, there was a 36% change in the volume of the dose-painting target delineated at 50%-of-max-SUV (ROI(50%)). The results of these studies indicate that the contrast recovery and spatial distributions of tracer within PET images are susceptible to changes in the position of the patient/tumour at the time of imaging. As such, random set-up errors in HN patients can result in reduced correlation between subsequent image-studies of the same tumour.

A phantom model demonstration of tomotherapy dose painting delivery, including managed respiratory motion without motion management.

The aim of the study was to demonstrate a potential alternative scenario for accurate dose-painting (non-homogeneous planned dose) delivery at 1 cm beam width with helical tomotherapy (HT) in the presence of 1 cm, three-dimensional, intra-fraction respiratory motion, but without any active motion management. A model dose-painting experiment was planned and delivered to the average position (proper phase of a 4DCT scan) with three spherical PTV levels to approximate dose painting to compensate for hypothetical hypoxia in a model lung tumor. Realistic but regular motion was produced with the Washington University 4D Motion Phantom. A small spherical Virtual Water phantom was used to simulate a moving lung tumor inside of the LUNGMAN anthropomorphic chest phantom to simulate realistic heterogeneity uncertainties. A piece of 4 cm Gafchromic EBT film was inserted into the 6 cm diameter sphere. TomoTherapy, Inc., DQA software was used to verify the delivery performed on a TomoTherapy Hi-Art II device. The dose uncertainty in the purposeful absence of motion management and in the absence of large, low frequency drifts (periods greater than the beam width divided by the couch velocity) or randomness in the breathing displacement yields very favorable results. Instead of interference effects, only small blurring is observed because of the averaging of many breathing cycles and beamlets and the avoidance of interference. Dose painting during respiration with helical tomotherapy is feasible in certain situations without motion management. A simple recommendation is to make respiration as regular as possible without low frequency drifting. The blurring is just small enough to suggest that it may be acceptable to deliver without motion management if the motion is equal to the beam width or smaller (at respiration frequencies) when registered to the average position.