Technical Note: Impact of impurities on Yttrium-90 glass microsphere activity quantitation.

Background: Glass Y microspheres are produced with known radionuclide impurities. These impurities are not independently monitored. Clinical instruments, including ionization chamber dose calibrators and positron emmission tomography (PET) cameras, can be much more sensitive in detecting signals from these impurities than to signals from Y itself.

Radiochemical Quality Control Methods for Radium-223 and Thorium-227 Radiotherapies.

The majority of radiopharmaceuticals for use in disease detection and targeted treatment undergo a single radioactive transition (decay) to reach a stable ground state. Complex emitters, which produce a series of daughter radionuclides, are emerging as novel radiopharmaceuticals. The need for validation of chemical and radiopurity with such agents using common quality control instrumentation is an area of active investigation.

SUVfdg: A standard-uptake-value (SUV) body habitus normalizer specific to fluorodeoxyglucose (FDG) in humans.

Purpose: To devise a new body-habitus normalizer to be used in the calculation of an SUV that is specific to the PET tracer 18F-FDG.

Methods: A cohort of 481-patients was selected for analysis of 18F-FDG uptake into tissues unaffected by their disease. Among these, 65-patients had only brain concentrations measured and the remaining 416 were randomly divided into an 86-patient test set and a 330-patient training set.

Optimizing reconstruction parameters for quantitative I-PET in the presence of therapeutic doses of I.

Background: The goal of this work was to determine the quantitative accuracy and optimal reconstruction parameters for I-PET imaging in the presence of therapeutic levels of I. In this effort, images were acquired on a GE D710 PET/CT scanner using a NEMA IEC phantom with spheres containing I and increasing amounts of I activity in the background. At each activity level, two scans were acquired, one with the phantom centered in the field of view (FOV) and one 11.

Patient Size-Dependent Dosimetry Methodology Applied to F-FDG Using New ICRP Mesh Phantoms.

Despite the known influence of anatomic variability on internal dosimetry, dosimetry for F-FDG and other diagnostic radiopharmaceuticals is routinely derived using reference phantoms, which embody population-averaged morphometry for a given age and sex. Moreover, phantom format affects dosimetry estimates to varying extent. Here, we applied newly developed mesh format reference phantoms and a patient-dependent phantom library to assess the impact of height, weight, and body contour variation on dosimetry of F-FDG.

Comparison of Ga-DOTA-JR11 PET/CT with dosimetric Lu-satoreotide tetraxetan (Lu-DOTA-JR11) SPECT/CT in patients with metastatic neuroendocrine tumors undergoing peptide receptor radionuclide therapy.

Purpose: Paired imaging/therapy with radiolabeled somatostatin receptor (SSTR) antagonists is a novel approach in neuroendocrine tumors (NETs). The aim of this study was to compare tumor uptake of Ga-DOTA-JR11 and Lu-satoreotide tetraxetan (Lu-DOTA-JR11) in patients with NETs.

Methods: As part of a prospective clinical trial, 20 patients with metastatic NETs underwent Ga-DOTA-JR11 PET/CT and serial imaging with Lu-satoreotide tetraxetan.

First-in-Humans Trial of Dasatinib-Derivative Tracer for Tumor Kinase-Targeted PET.

We developed a first-of-kind dasatinib-derivative imaging agent, F-SKI-249380 (F-SKI), and validated its use for noninvasive in vivo tyrosine kinase-targeted tumor detection in preclinical models. In this study, we assessed the feasibility of using F-SKI for PET imaging in patients with malignancies. Five patients with a prior diagnosis of breast cancer, renal cell cancer, or leukemia underwent whole-body PET/CT imaging 90 min after injection of F-SKI (mean, 241.

F-Fluorocholine PET uptake correlates with pathologic evidence of recurrent tumor after stereotactic radiosurgery for brain metastases.

Purpose: Radiographic changes of brain metastases after stereotactic radiosurgery (SRS) can signify tumor recurrence and/or radiation necrosis (RN); however, standard imaging modalities cannot easily distinguish between these two entities. We investigated whether F-Fluorocholine uptake in surgical samples of the resected lesions correlates with pathologic evidence of recurrent tumor and PET imaging.

Methods: About 14 patients previously treated with SRS that developed radiographic changes were included.

Preclinical efficacy of hK2 targeted [Lu]hu11B6 for prostate cancer theranostics.

Androgen ablating drugs increase life expectancy in men with metastatic prostate cancer, but resistance inevitably develops. In a majority of these recurrent tumors, the androgen axis is reactivated in the form of increased androgen receptor (AR) expression. Targeting proteins that are expressed as a down-stream effect of AR activity is a promising rationale for management of this disease.

Proposed changes to the ACR phantom filling procedure for more accurate and consistent activity concentrations.

Objectives: The phantom filling procedures currently specified by the American College of Radiology (ACR) for its PET accreditation program unnecessarily limit how tight the tolerances can be made on the accuracy requirements for the concentrations measured in the resultant images.

Methods: New procedures are proposed to improve the accuracy and consistency of the concentrations within the phantom at the time of imaging. These improvements are gained by exchanging the difficult process of accurately measuring a dose with the more easily achieved accurate measurements of time and liquid volume to control final radioactivity concentrations.

Biodistribution and radiation dose estimates for Ga-DOTA-JR11 in patients with metastatic neuroendocrine tumors.

Purpose: Somatostatin receptor antagonists have shown promise for imaging neuroendocrine tumors (NETs) in preclinical studies, but clinical data is still very limited. In this study, we assess the feasibility of using the novel somatostatin antagonist Ga-DOTA-JR11 for PET imaging of NETs.

Methods: Twenty patients with advanced NETs underwent whole-body PET/CT imaging 60 min after injection of 169 MBq (median) Ga-DOTA-JR11 as part of a prospective study.

Feed-forward alpha particle radiotherapy ablates androgen receptor-addicted prostate cancer.

Human kallikrein peptidase 2 (hK2) is a prostate specific enzyme whose expression is governed by the androgen receptor (AR). AR is the central oncogenic driver of prostate cancer (PCa) and is also a key regulator of DNA repair in cancer. We report an innovative therapeutic strategy that exploits the hormone-DNA repair circuit to enable molecularly-specific alpha particle irradiation of PCa.

Reproducibility and Repeatability of Semiquantitative F-Fluorodihydrotestosterone Uptake Metrics in Castration-Resistant Prostate Cancer Metastases: A Prospective Multicenter Study.

F-fluorodihydrotestosterone (F-FDHT) is a radiolabeled analog of the androgen receptor's primary ligand that is currently being credentialed as a biomarker for prognosis, response, and pharmacodynamic effects of new therapeutics. As part of the biomarker qualification process, we prospectively assessed its reproducibility and repeatability in men with metastatic castration-resistant prostate cancer. We conducted a prospective multiinstitutional study of metastatic castration-resistant prostate cancer patients undergoing 2 (test/retest) F-FDHT PET/CT scans on 2 consecutive days.

In Vivo PET Assay of Tumor Glutamine Flux and Metabolism: In-Human Trial of F-(2S,4R)-4-Fluoroglutamine.

Purpose To assess the clinical safety, pharmacokinetics, and tumor imaging characteristics of fluorine 18-(2S,4R)-4-fluoroglutamine (FGln), a glutamine analog radiologic imaging agent. Materials and Methods This study was approved by the institutional review board and conducted under a U.S.

Carbon nanotubes exhibit fibrillar pharmacology in primates.

Nanomedicine rests at the nexus of medicine, bioengineering, and biology with great potential for improving health through innovation and development of new drugs and devices. Carbon nanotubes are an example of a fibrillar nanomaterial poised to translate into medical practice. The leading candidate material in this class is ammonium-functionalized carbon nanotubes (fCNT) that exhibits unexpected pharmacological behavior in vivo with important biotechnology applications.

Monitoring early response to chemoradiotherapy with F-FMISO dynamic PET in head and neck cancer.

Purpose: There is growing recognition that biologic features of the tumor microenvironment affect the response to cancer therapies and the outcome of cancer patients. In head and neck cancer (HNC) one such feature is hypoxia. We investigated the utility of F-fluoromisonidazole (FMISO) dynamic positron emission tomography (dPET) for monitoring the early microenvironmental response to chemoradiotherapy in HNC.

Relaxed ordered subset preconditioned alternating projection algorithm for PET reconstruction with automated penalty weight selection.

Purpose: Performance of the preconditioned alternating projection algorithm (PAPA) using relaxed ordered subsets (ROS) with a non-smooth penalty function was investigated in positron emission tomography (PET). A higher order total variation (HOTV) regularizer was applied and a method for unsupervised selection of penalty weights based on the measured data is introduced.

Methods: A ROS version of PAPA with HOTV penalty (ROS-HOTV-PAPA) for PET image reconstruction was developed and implemented.

Multiparametric Imaging of Tumor Hypoxia and Perfusion with F-Fluoromisonidazole Dynamic PET in Head and Neck Cancer.

Tumor hypoxia and perfusion are independent prognostic indicators of patient outcome. We developed the methodology for and investigated the utility of multiparametric imaging of tumor hypoxia and perfusion with F-fluoromisonidazole (F-FMISO) dynamic PET (dPET) in head and neck cancer. One hundred twenty head and neck cancer patients underwent 0- to 30-min F-FMISO dPET in a customized immobilization mask, followed by 10-min static acquisitions starting at 93 ± 6 and 160 ± 13 min after injection.

Dynamic PET simulator via tomographic emission projection for kinetic modeling and parametric image studies.

Purpose: To develop and evaluate a fast and simple tool called dpetstep (Dynamic PET Simulator of Tracers via Emission Projection), for dynamic PET simulations as an alternative to Monte Carlo (MC), useful for educational purposes and evaluation of the effects of the clinical environment, postprocessing choices, etc., on dynamic and parametric images.

Methods: The tool was developed in matlab using both new and previously reported modules of petstep (PET Simulator of Tracers via Emission Projection).

Targeted fibrillar nanocarbon RNAi treatment of acute kidney injury.

RNA interference has tremendous yet unrealized potential to treat a wide range of illnesses. Innovative solutions are needed to protect and selectively deliver small interfering RNA (siRNA) cargo to and within a target cell to fully exploit siRNA as a therapeutic tool in vivo. Herein, we describe ammonium-functionalized carbon nanotube (fCNT)-mediated transport of siRNA selectively and with high efficiency to renal proximal tubule cells in animal models of acute kidney injury (AKI).

PETSTEP: Generation of synthetic PET lesions for fast evaluation of segmentation methods.

Purpose: This work describes PETSTEP (PET Simulator of Tracers via Emission Projection): a faster and more accessible alternative to Monte Carlo (MC) simulation generating realistic PET images, for studies assessing image features and segmentation techniques.

Methods: PETSTEP was implemented within Matlab as open source software. It allows generating three-dimensional PET images from PET/CT data or synthetic CT and PET maps, with user-drawn lesions and user-set acquisition and reconstruction parameters.

A recommendation for revised dose calibrator measurement procedures for 89Zr and 124I.

Because of their chemical properties and multiday half lives, iodine-124 and zirconium-89 are being used in a growing number of PET imaging studies. Some aspects of their quantitation, however, still need attention. For (89)Zr the PET images should, in principle, be as quantitatively accurate as similarly reconstructed 18F measurements.