Modeling analysis of platinum-195m for targeting individual blood-borne cells in adjuvant radioimmunotherapy.

Unlabelled: The inability to eradicate a population of single, isolated, blood-borne tumor cells with the radionuclides currently in use may limit the efficacy of adjuvant radioimmunotherapy. We have examined the possibility of sterilizing single blood-borne cells using surface-bound emitters of Auger and conversion electrons.

Methods: The number of cell-surface decays required for 99% sterilization was found by using the linear-quadratic model of cell survival (alpha = 0.

Image registration of SPECT and CT images using an external fiduciary band and three-dimensional surface fitting in metastatic thyroid cancer.

Image registration of 131I SPECT with CT scans was performed in a patient with metastatic thyroid carcinoma using an external fiduciary band and a three-dimensional surface-fitting algorithim. Areas of metastatic disease taking up 131I were accurately localized to the liver, lungs and vertebral bodies; providing information that could not be obtained by planar or SPECT images alone. Based on these findings, further invasive diagnostic procedures were not performed, therefore considerably altering management in this patient.

Calculated and TLD-based absorbed dose estimates for I-131-labeled 3F8 monoclonal antibody in a human neuroblastoma xenograft nude mouse model.

Preclinical evaluation of the therapeutic potential of radiolabeled antibodies is commonly performed in a xenografted nude mouse model. To assess therapeutic efficacy it is important to estimate the absorbed dose to the tumor and normal tissues of the nude mouse. The current study was designed to accurately measure radiation does to human neuroblastoma xenografts and normal organs in nude mice treated with I-131-labeled 3F8 monoclonal antibody (MoAb) against disialoganglioside GD2 antigen.

Clinical validation of SPECT and CT/MRI image registration in radiolabeled monoclonal antibody studies of colorectal carcinoma.

Unlabelled: Registration methods combine the anatomic localizing ability of CT or MRI with SPECT images of radiolabeled monoclonal antibodies (Mabs), allowing the accurate staging of patients prior to surgery or following treatment.

Methods: Twenty-four patients (15 males and 9 females, mean age 55 yr, range 29-70 yr) were studied with this technique. Ten patients had suspected colorectal cancer recurrence and were infused with 10 mCi of 131I-CC49 prior to staging laparotomy.

Current status of radioimmunotherapy.

Radioimmunotherapy with radiolabeled monoclonal antibodies is increasingly effective for hematopoietic tumors, with a number of investigators reporting persistent major responses. Radioimmunotherapy for solid tumors has been more difficult and only an occasional major response has been reported and these have so far not been persistent. Toxicity is predominantly hematopoietic, with platelets being most sensitive to the effects of radiation.

Clinical applications of fusion imaging in oncology.

Recent developments in tumor imaging, made possible by advances in instrumentation and radiopharmaceuticals, has led to an increasing need for accurate anatomic correlation of single photon emission computed tomography (SPECT) and positron emission tomography (PET) images. Fusion imaging permits the functional strengths of SPECT and PET to be combined with the anatomic resolution of computed tomography (CT) and magnetic resonance imaging (MRI). Clinical applications of fusion imaging include the evaluation of brain tumors, lymphoma, hepatic lesions and monoclonal antibody studies.

A phase 1B trial of humanized monoclonal antibody M195 (anti-CD33) in myeloid leukemia: specific targeting without immunogenicity.

This trial studied the biodistribution, pharmacology, toxicity, immunogenicity, and biologic characteristics of a trace-labeled, anti-CD33, humanized monoclonal antibody M195 (Hu-M195) in patients with relapsed and refractory myeloid leukemia. Hu-M195 is a computer-modeled, "complementarity-determining region-grafted," IgG1, humanized version of M195. M195 is a murine monoclonal antibody that reacts with CD33, a 67-kD glycoprotein expressed on early myeloid progenitor cells and myeloid leukemia (acute myelogenous leukemia and chronic myelogenous leukemia) cells, but not normal stem cells.

Three-dimensional dosimetry for radioimmunotherapy treatment planning.

Absorbed-dose calculations for radioimmunotherapy are generally based on tracer imaging studies of the labeled antibody. Such calculations yield estimates of the average dose to normal and target tissues assuming idealized geometries for both the radioactivity source volume and the target volume. This work describes a methodology that integrates functional information obtained from SPECT or PET with anatomical information from CT or MRI.

Bone marrow dosimetry for radioimmunotherapy: theoretical considerations.

In most implementations of radioimmunotherapy, the red marrow is the dose-limiting organ. Estimates of the radioactivity concentration in this organ are usually based on blood sampling or bone marrow biopsy. This work presents a simple equation which may be used to calculate the red marrow-to-blood activity concentration ratio given the hematocrit and the red marrow extracellular fluid fraction of a patient.

Modeling and dosimetry of monoclonal antibody M195 (anti-CD33) in acute myelogenous leukemia.

Individual patient response to radioimmunotherapy is influenced by each patient's tumor burden, antibody clearance kinetics and the antibody-antigen interaction. In hematologic malignancies, wherein antibody access to tumor-cell associated antigen is rapid, mathematical modeling may provide a quantitative basis for assessing the impact of patient variability on a particular therapeutic protocol. Compartmental modeling analysis of antibody pharmacokinetics from a Phase I trial of 131I-labeled monoclonal antibody, M195 (anti-CD33), was used to estimate tumor burden in cases of acute myelogenous leukemia and the absorbed dose in liver, spleen and red marrow.

Treatment of leukemia with radiolabeled monoclonal antibodies.

In contrast to radioimmunotherapy of solid disease, wherein the primary obstacle to success is access of radiolabeled antibody to antigen-positive cells, in the treatment of leukemia delivering a lethal absorbed dose to the isolated cell appears to be the primary obstacle. The isolated cell is defined as one that is exposed only to self-irradiation (from internalized or surface-bound radiolabeled antibody) and to irradiation from free antibody in the blood. It is isolated in the sense that the particulate (beta, electron, alpha) emissions from its nearest neighboring antigen-positive cell do not contribute to its absorbed dose.

Plasmapheresis in radioimmunotherapy of micrometastases: a mathematical modeling and dosimetrical analysis.

The feasibility of combining plasmapheresis with a large administration of radiolabeled antibody in order to overcome the "binding-site" barrier to antibody penetration in targeting hematologically distributed micrometastases is examined. In such a strategy, intravenous administration of excess radiolabeled antibody, to saturate antigen sites on the cell cluster periphery, is followed by removal of unbound antibody from the plasma, by plasmapheresis, to reduce the absorbed dose to the red marrow. Plasma antibody kinetics are simulated by a non-linear compartmental model representing free and antigen-bound antibody.

Treatment planning for internal radionuclide therapy: three-dimensional dosimetry for nonuniformly distributed radionuclides.

A calculational approach is described that provides the spatially varying radiation absorbed dose, presented as isodose contours superimposed on CT images, from nonuniform and/or irregular cumulated activity distributions. CT images are read from magnetic tape and are displayed on a high-resolution color graphics display monitor. Source tissue geometries are defined on a series of contiguous CT images automatically (by an edge detection algorithm) or manually (using a trackball), thereby obtaining a three-dimensional representation of the various source volumes of activity.

Quantitative SPECT in radiation dosimetry.

Accurate and precise radiation dosimetry is critical for the successful therapeutic application of systemically administered radionuclides, including, of course, radionuclides in the form of radiolabeled antibody. This requires determination, based on discrete serial measurements, of the time-dependent concentrations and/or total amounts of radioactivity in situ in order to calculate source region cumulated activities. Based on extensive studies (with clinically realistic numbers of counts and accuracies of the order of 10%) in simple geometric phantoms, in complex anthropomorphic phantoms, in animal models, and in humans, quantitative rotating scintillation camera-based single-photon emission computed tomography (SPECT) now appears to be a practical approach to such measurements.

Evaluation of [1-11C]-alpha-aminoisobutyric acid for tumor detection and amino acid transport measurement: spontaneous canine tumor studies.

Alpha-aminoisobutyric acid (AIB), or alpha-methyl alanine, is a nonmetabolized amino acid transported into cells, particularly malignant cells, predominantly by the 'A' amino acid transport system. Since it is not metabolized, [1-11C]-AIB can be used to quantify A-type amino acid transport into cells using a relatively simple compartmental model and quantitative imaging procedures (e.g.

Biological analysis and dosimetry for 15O-labeled O2, CO2, and CO gases administered continuously by inhalation.

Estimates of radiation absorbed dose have been determined for the steady-state distribution of oxygen-15 (T1/2 = 122 sec) from inhalation of molecular oxygen, 15O2; carbon dioxide, C15O2; and carbon monoxide, C15O. Biodistribution data for 15O-labeled water, produced by the metabolism of oxygen and from CO2 by pulmonary carbonic anhydrase, were used. Lung gas and intravascular activities are also included.