Radioimmunoscintigraphy and Pretreatment Dosimetry of I-Omburtamab for Planning Treatment of Leptomeningeal Disease.

Radiolabeled antibody treatment with I-omburtamab, administered intraventricularly into the cerebrospinal fluid (CSF) space, can deliver therapeutic absorbed doses to sites of leptomeningeal disease. Assessment of distribution and radiation dosimetry is a key element in optimizing such treatments. Using a theranostic approach, we performed pretreatment I-omburtamab imaging and dosimetric analysis in patients before therapy.

Enhancing Radioiodine Incorporation in -Mutant, Radioiodine-Refractory Thyroid Cancers with Vemurafenib and the Anti-ErbB3 Monoclonal Antibody CDX-3379: Results of a Pilot Clinical Trial.

Oncogenic activation of mitogen-activated protein kinase (MAPK) signaling is associated with radioiodine refractory (RAIR) thyroid cancer. Preclinical models suggest that activation of the receptor tyrosine kinase erbB-3 (HER3) mitigates the MAPK pathway inhibition achieved by BRAF inhibitors in mutant thyroid cancers. We hypothesized that combined inhibition of BRAF and HER3 using vemurafenib and the human monoclonal antibody CDX-3379, respectively, would potently inhibit MAPK activation and restore radioactive iodine (RAI) avidity in patients with mutant RAIR thyroid cancer.

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.

Biodistribution and Dosimetry of Intraventricularly Administered I-Omburtamab in Patients with Metastatic Leptomeningeal Tumors.

Radiation dose estimations are key for optimizing therapies. We studied the role of I-omburtamab (8H9) given intraventricularly in assessing the distribution and radiation doses before I-omburtamab therapy in patients with metastatic leptomeningeal disease and compared it with the estimates from cerebrospinal fluid (CSF) sampling. Patients with histologically proven malignancy and metastatic disease to the central nervous system or leptomeninges who met eligibility criteria for I-omburtamab therapy underwent immuno-PET imaging with I-8H9 followed by I-8H9 antibody therapy.

Vemurafenib Redifferentiation of BRAF Mutant, RAI-Refractory Thyroid Cancers.

Context: BRAFV600E mutant thyroid cancers are often refractory to radioiodine (RAI).

Objectives: To investigate the utility and molecular underpinnings of enhancing lesional iodide uptake with the BRAF inhibitor vemurafenib in patients with RAI-refractory (RAIR).

Design: This was a pilot trial that enrolled from June 2014 to January 2016.

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.

Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer.

Background: Metastatic thyroid cancers that are refractory to radioiodine (iodine-131) are associated with a poor prognosis. In mouse models of thyroid cancer, selective mitogen-activated protein kinase (MAPK) pathway antagonists increase the expression of the sodium-iodide symporter and uptake of iodine. Their effects in humans are not known.

Quantitative modeling of Cerenkov light production efficiency from medical radionuclides.

There has been recent and growing interest in applying Cerenkov radiation (CR) for biological applications. Knowledge of the production efficiency and other characteristics of the CR produced by various radionuclides would help in accessing the feasibility of proposed applications and guide the choice of radionuclides. To generate this information we developed models of CR production efficiency based on the Frank-Tamm equation and models of CR distribution based on Monte-Carlo simulations of photon and β particle transport.

Salivary gland side effects commonly develop several weeks after initial radioactive iodine ablation.

Unlabelled: Salivary gland side effects (SSEs) can be a source of significant morbidity in thyroid cancer patients receiving radioactive iodine (RAI) for remnant ablation or therapy. However, the incidence, time course, and ultimate resolution of SSEs that develop in the first few months after a single administered activity of RAI for remnant ablation has not be adequately defined.

Methods: We retrospectively reviewed the clinical records of patients after RAI remnant ablation (RRA) to determine the incidence of salivary gland-related side effects reported within the first year of RRA, the dose-response relationship between administered activity and specific SSEs, and the incidence of specific SSEs based on the method of preparation for remnant ablation (recombinant human thyroid-stimulating hormone [rhTSH] vs.

The Role of Iodine-124-Positron Emission Tomography Imaging in the Management of Patients with Thyroid Cancer.

Molecular imaging is the visualization, characterization, and measurement of biologic processes at the molecular and cellular levels in human beings and other living systems. In thyroid cancer, this includes imaging iodine transport, which is active in about 80% of well-differentiated thyroid malignancies. Iodine-124 imaging with positron emission tomography (I-124-PET) is ideal for this purpose because PET provides tomographic images with spatial and contrast resolution.

Prediction of absorbed dose to normal organs in thyroid cancer patients treated with 131I by use of 124I PET and 3-dimensional internal dosimetry software.

Unlabelled: The objective of this work was to determine normal organ (131)I dosimetry in patients undergoing radioiodide therapy for thyroid cancer by use of serial scanning with (124)I PET.

Methods: A total of 26 patients who had papillary and follicular metastatic thyroid cancer and who were already enrolled in a Memorial Sloan-Kettering Cancer Center (131)I thyroid cancer protocol were selected for this study. Imaging before (131)I therapy consisted of multiple, whole-body (124)I PET studies over a period of 2-8 d, an (18)F-FDG PET scan and, for some, a diagnostic CT scan.

Empiric radioactive iodine dosing regimens frequently exceed maximum tolerated activity levels in elderly patients with thyroid cancer.

Unlabelled: Although 131I-iodine (RAI) therapy is a mainstay in the treatment of metastatic thyroid cancer, there is controversy regarding the maximum activity that can safely be administered without dosimetric determination of the maximum tolerable activity (MTA). At most institutions, a fixed empiric dosing strategy is often used, with administered activities ranging from 5.55 to 9.

PET-based radiation dosimetry in man of 18F-fluorodihydrotestosterone, a new radiotracer for imaging prostate cancer.

Unlabelled: 16 beta-fluoro-5 alpha-dihydrotestosterone (FDHT) is a promising new PET radiopharmaceutical for the imaging of prostate cancer. A recent clinical trial provided the opportunity for refinement of normal-tissue radiation-absorbed dose estimates based on quantitative PET. The objective of the current study was to derive estimates of normal-tissue absorbed doses for (18)F-FDHT administered to patients with advanced prostate cancer.

Patient-specific dosimetry for 131I thyroid cancer therapy using 124I PET and 3-dimensional-internal dosimetry (3D-ID) software.

Unlabelled: Compared with conventional, whole-organ, S-factor-based dosimetry, 3-dimensional (3D), patient-specific dosimetry better accounts for radionuclide distribution and anatomic patient variability. Its accuracy, however, is limited by the quality of the cumulated activity information that is provided as input. This input has typically been obtained from SPECT and planar imaging studies.

Tumor localization of 16beta-18F-fluoro-5alpha-dihydrotestosterone versus 18F-FDG in patients with progressive, metastatic prostate cancer.

Unlabelled: This trial was an initial assessment of the feasibility, in vivo targeting, and biokinetics of 16beta-(18)F-fluoro-5alpha-dihydrotestosterone ((18)F-FDHT) PET in patients with metastatic prostate cancer to assess androgen receptor expression.

Methods: Seven patients with progressive clinically metastatic prostate cancer underwent (18)F-FDG and (18)F-FDHT PET scans in addition to conventional imaging methods. Three patients had their studies repeated 1 mo later, 2 while on testosterone therapy, and the third after treatment with 17-allylamino-17-demethoxygeldanamycin (17-AAG).

Quantitative imaging of bromine-76 and yttrium-86 with PET: a method for the removal of spurious activity introduced by cascade gamma rays.

Positron Emission Tomography of bromine-76 and yttrium-86 results in the detection of coincident events that are not strictly associated with annihilation photon pairs. Instead, these coincidences occur because prompt gamma rays emitted by these nuclides result in cascades of photons that are emitted within the timing window of the PET scanner. Pairs of detected photons from these cascades are not angularly correlated and therefore contain little information regarding the location of their source.

Changes in FDG Tumor Uptake during and after Fractionated Radiation Therapy in a Rodent Tumor Xenograft.

OBJECTIVE: The uptake of FDG was measured before, during, and after fractionated radiation in order to evaluate the potential of FDG-PET imaging as an indicator of tumor response.METHODS: The study was performed with nude rats bearing the human neuroblastoma BE(2)C tumor xenografts. Tumors were irradiated with 10 fractions of 2 Gy using a 320 kV(p) X-ray unit.

Differential Metabolism and Pharmacokinetics of L-[1-(11)C]-Methionine and 2-[(18)F] Fluoro-2-deoxy-D-glucose (FDG) in Androgen Independent Prostate Cancer.

Metabolic imaging with positron emission tomography (PET) for the staging and monitoring of treatment response has important implications in clinical oncology. The choice of radiotracer is likely to be critically important. The objective of our study was to compare the pharmacokinetics of C-11-methionine with FDG in a group of androgen independent patients with metastatic prostate cancer, to determine the differential metabolism of the two tracers, and to determine the optimal time of imaging after injection in treated and untreated patients.

A retrospective review of the effectiveness of recombinant human TSH as a preparation for radioiodine thyroid remnant ablation.

Unlabelled: Radioiodine remnant ablation (RRA) is frequently used after a thyroidectomy for differentiated thyroid carcinoma because it has been reported to reduce the number of local recurrences and to increase overall survival. Although the traditional method of preparation for RRA is thyroid hormone withdrawal, several physicians at our medical center have offered the option of having RRA after preparation by recombinant human thyroid-stimulating hormone (thyrotropin; TSH) over the past 2 y. During this same time period, other patients at our center were prepared for RRA by hormone withdrawal.