Microdosimetry of astatine-211 single-cell irradiation: role of daughter polonium-211 diffusion.

A microdosimetric analysis of previously published data on 211At-albumin, free 211At, and 211At-C215 irradiation of Colo-205 cells in a slowly rotating single-cell suspension is presented. A custom-built computer program based on the Monte Carlo method was used to simulate the irradiation and the energy deposition in individual cell nuclei. Separate simulations were made for the assumption that the 211Po atom stays in the position where it is created, and that it diffuses away.

Correction for oral contrast artifacts in CT attenuation-corrected PET images obtained by combined PET/CT.

Unlabelled: Recent studies have shown increased artifacts in CT attenuation-corrected (CTAC) PET images acquired with oral contrast agents because of misclassification of contrast as bone. We have developed an algorithm, segmented contrast correction (SCC), to properly transform CT numbers in the contrast regions from CT energies (40-140 keV) to PET energy at 511 keV.

Methods: A bilinear transformation, equivalent to that supplied by the PET/CT scanner manufacturer, for the conversion of linear attenuation coefficients of normal tissues from CT to PET energies was optimized for BaSO(4) contrast agent.

From PET detectors to PET scanners.

This review describes the properties of available and emerging radiation detector and read-out technologies and discusses how they may affect PET scanner performance. After a general introduction, there is a section in which the physical properties of several different detector scintillators are compared. This is followed by a discussion of recent advances in read-out electronics.

Reduction of respiratory motion artifacts in PET imaging of lung cancer by respiratory correlated dynamic PET: methodology and comparison with respiratory gated PET.

Unlabelled: This study proposes a new method to reduce respiratory motion artifacts in PET images of lung cancer. The method is referred to as respiratory-correlated dynamic PET (RCDPET). RCDPET enables the acquisition of 4-dimensional PET data without the need for a respiratory tracking device.

A stereotactic method for the three-dimensional registration of multi-modality biologic images in animals: NMR, PET, histology, and autoradiography.

The objective of this work was to develop and then validate a stereotactic fiduciary marker system for tumor xenografts in rodents which could be used to co-register magnetic resonance imaging (MRI), PET, tissue histology, autoradiography, and measurements from physiologic probes. A Teflon fiduciary template has been designed which allows the precise insertion of small hollow Teflon rods (0.71 mm diameter) into a tumor.

Iodine-124-labeled iodo-azomycin-galactoside imaging of tumor hypoxia in mice with serial microPET scanning.

Tumor hypoxia, present in many human cancers, can lead to resistance to radiation and chemotherapy, is associated with a more aggressive tumor phenotype and is an independent prognostic factor of clinical outcome. It is therefore important to identify and localize tumor hypoxia in cancer patients. In the current study, serial microPET imaging was used to evaluate iodine-124-labeled iodo-azomycin-galactoside ((124)I-IAZG) (4.

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.

Radiation Dose Assessment for I-131 Therapy of Thyroid Cancer Using I-124 PET Imaging.

The goal for this work was to develop a method to determine the feasibility of estimating absorbed dose distribution of I-131 thyroid therapy using I-124 PET images of residual thyroid lesions with the dose constraint of 200 cGy to blood, that is a surrogate for bone marrow toxicity. A dose response study has been carried out on 3 patients with papillary thyroid carcinoma. Those patients were given 15-37 MBq of I-124 along with 74-185 MBq of I-131.

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.

Tumor Treatment Response Based on Visual and Quantitative Changes in Global Tumor Glycolysis Using PET-FDG Imaging. The Visual Response Score and the Change in Total Lesion Glycolysis.

"Functional" tumor treatment response parameters have been developed to measure treatment induced biochemical changes in the entire tumor mass, using positron emission tomography (PET) and [F-18] fludeoxyglucose (FDG). These new parameters are intended to measure global changes in tumor glycolysis. The response parameters are determined by comparing the pre- and posttreatment PET-FDG images either visually from the change in image appearance in the region of the tumor, or quantitatively based on features of the calibrated digital PET image.

Targeted alpha particle immunotherapy for myeloid leukemia.

Unlike beta particle-emitting isotopes, alpha emitters can selectively kill individual cancer cells with a single atomic decay. HuM195, a humanized anti-CD33 monoclonal antibody, specifically targets myeloid leukemia cells and has activity against minimal disease. When labeled with the beta-emitters (131)I and (90)Y, HuM195 can eliminate large leukemic burdens in patients, but it produces prolonged myelosuppression requiring hematopoietic stem cell transplantation at high doses.

Measurements of tumor tissue oxygen tension using a time-resolved luminescence-based optical oxylite probe: comparison with a paired survival assay.

Recently, a system that measures tissue oxygen tension using time-resolved luminescence-based optical sensors has become available commercially (Oxford Optronix, Oxford, England). Two experiments were conducted using this system. First, the oxygen tension distribution was measured in two tumor lines: a spontaneous mouse fibrosarcoma, FSa-II, and a human squamous cell carcinoma xenograft, FaDu.

Effect of respiratory gating on quantifying PET images of lung cancer.

Unlabelled: We have developed a new technique to gate lung 18F-FDG PET images in synchronization with the respiratory motion to reduce smearing due to breathing and improve quantitation of 18F-FDG uptake in lung lesions.

Methods: A camera-based respiratory gating system, the real-time position management (RPM), is used to monitor the respiratory cycle. The RPM provides a trigger to the PET scanner to initiate the gating cycle.

Iodination of annexin V for imaging apoptosis.

Unlabelled: Our goal in this investigation was to develop a method for iodinating annexin V that would be suitable for the in vivo detection of apoptosis.

Methods: Annexin V was iodinated with (125)I using 2 different techniques: direct iodination with IODO-BEADS, resulting in the iodination of tyrosine residues; and use of the Bolton-Hunter reagent, which binds to lysine. The active fraction of the labeled preparation was purified by affinity chromatography.

Effect of respiratory gating on reducing lung motion artifacts in PET imaging of lung cancer.

Positron emission tomography (PET) has shown an increase in both sensitivity and specificity over computed tomography (CT) in lung cancer. However, motion artifacts in the 18F fluorodioxydoglucose (FDG) PET images caused by respiration persists to be an important factor in degrading PET image quality and quantification. Motion artifacts lead to two major effects: First, it affects the accuracy of quantitation, producing a reduction of the measured standard uptake value (SUV).

Rationales, evidence, and design considerations for fractionated radioimmunotherapy.

Although fractionation can be used in a discrete radiobiologic sense, herein it is generally used in the broader context of administration of multiple, rather than single, doses of radionuclide for radioimmunotherapy (RIT) or other targeted radionuclide therapies. Fractionation is a strategy for overcoming heterogeneity of monoclonal antibody (MAb) distribution in the tumor and the consequent nonuniformity of tumor radiation doses. Additional advantages of fractionated RIT are the ability to 1) provide patient-specific radionuclide and radiation dosing, 2) control toxicity by titration of the individual patient, 3) reduce toxicity, 4) increase the maximum tolerated dose (MTD) for many patients, 5) increase tumor radiation dose and efficacy, and 6) prolong tumor response by permitting treatment over time.

Radiotherapy treatment planning for patients with non-small cell lung cancer using positron emission tomography (PET).

Purpose: Many patients with non-small cell lung cancer (NSCLC) receive external beam radiation therapy as part of their treatment. Three-dimensional conformal radiation therapy (3DCRT) commonly uses computed tomography (CT) to accurately delineate the target lesion and normal tissues. Clinical studies, however, indicate that positron emission tomography (PET) has higher sensitivity than CT in detecting and staging of mediastinal metastases.

Local detection of prostate cancer by positron emission tomography with 2-fluorodeoxyglucose: comparison of filtered back projection and iterative reconstruction with segmented attenuation correction.

Background: To compare filtered back projection (FBP) and iterative reconstruction with segmented attenuation correction (IRSAC) in the local imaging of prostate cancer by positron emission tomography with 2-fluorodeoxyglucose (FDG-PET).

Methods: We retrospectively identified 13 patients with primary (n=7) or recurrent (n=6) prostate cancer who had increased uptake in the prostate on FDG-PET performed without urinary catheterization, contemporaneous biopsy confirming the presence of active tumor in the prostate, and correlative cross-sectional imaging by MRI (n=8) or CT (n=5). FDG-PET images were reconstructed by FBP and IRSAC.

Using positron emission tomography with [(18)F]FDG to predict tumor behavior in experimental colorectal cancer.

This study investigates the relationship between FDG uptake as determined by positron emission tomography (PET) imaging and rates of tumor growth, cellular GLUT1 transporter density, and the activities of hexokinase and glucose-6-phosphatase in a solid tumor implant model. Five different human colorectal xenografts of different growth properties were implanted in athymic rats and evaluated by dynamic (18)F-FDG-PET. The phosphorylating and dephosphorylating activities of the key glycolytic enzymes, hexokinase and glucose-6-phosphatase, were measured in these tumor types by spectrophotometric assays and the expression of GLUT1 glucose transporter protein was determined by immunohistochemistry.

PET imaging of (86)Y-labeled anti-Lewis Y monoclonal antibodies in a nude mouse model: comparison between (86)Y and (111)In radiolabels.

Unlabelled: Absorbed doses in (90)Y radioimmunotherapy are usually estimated by extrapolating from (111)In imaging data. PET using (86)Y (beta(+) 33%; half-life, 14.7 h) as a surrogate radiolabel could be a more accurate alternative.

Relative therapeutic efficacy of (125)I- and (131)I-labeled monoclonal antibody A33 in a human colon cancer xenograft.

Unlabelled: A33, a monoclonal antibody that targets colon carcinomas, was labeled with (125)I or (131)I and the relative therapeutic efficacy of the 2 radiolabeled species was compared in a human colon cancer xenograft system.

Methods: Nude mice bearing human SW1222 colon carcinoma xenografts were administered escalating activities of (125)I-A33 (9.25-148 MBq) or (131)I-A33 (0.

Imaging transcriptional regulation of p53-dependent genes with positron emission tomography in vivo.

A noninvasive method for molecular imaging of the activity of different signal transduction pathways and the expression of different genes in vivo would be of considerable value. It would aid in understanding the role specific genes and signal transduction pathways have in various diseases, and could elucidate temporal dynamics and regulation at different stages of disease and during various therapeutic interventions. We developed and assessed a method for monitoring the transcriptional activation of endogenous genes by positron-emission tomography (PET) imaging.

Estimate of absorbed dose based on two-dimensional autoradiographic information in internal radionuclide therapy.

In radiation therapies using radionuclides emitting short-range particles, such as radioimmunotherapy or boron neutron capture therapy, the biological effects are strongly affected by the heterogeneity of the absorbed dose distribution delivered to tumor cells. The three-dimensional (3D) information of the source distribution at the cellular level is required to accurately determine the absorbed dose distribution to the individual tumor cells. Two-dimensional distribution of cell and nuclide with a resolution of 1 microm can be obtained from individual tissue sections by microautoradiography.

Hypoxia-Induced increase in FDG uptake in MCF7 cells.

Unlabelled: Recent clinical data indicate that tumor hypoxia negatively affects the treatment outcome of both radiotherapy and surgery in various cancers, emphasizing the need for noninvasive detection of tumor hypoxia. Several studies have shown an increased uptake of FDG in hypoxic regions of xenografts, suggesting the use of PET with FDG as a potential technique. In this study, we examine the mechanism underlying the hypoxia-induced increase of FDG uptake in the human breast carcinoma cell line MCF7.

8. A Spherical Coordinate System for Tumor Identification in Positron Emission Tomography (PET) Imaging.

Purpose: PET can be useful in determining the progression of malignant disease over time as well as the response to therapy. To achieve this, the physician must be able to unambiguously identify and characterize individual tumors among several different scans.Methods: We have developed a spherical coordinate system for identifying individual tumor sites on PET scans, using the carina on the transmission scan as a point of origin.