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R R Raylman

Publications and source records attributed to R R Raylman.

11 recordsLinked to original sources

Exposure to strong static magnetic field slows the growth of human cancer cells in vitro.

Proposals to enhance the amount of radiation dose delivered to small tumors with radioimmunotherapy by constraining emitted electrons with very strong homogeneous static magnetic fields has renewed interest in the cellular effects of prolonged exposures to such fields. Past investigations have not studied the effects on tumor cell growth of lengthy exposures to very high magnetic fields. Three malignant human cell lines, HTB 63 (melanoma), HTB 77 IP3 (ovarian carcinoma), and CCL 86 (lymphoma: Raji cells), were exposed to a 7 Tesla uniform static magnetic field for 64 hours. Following exposure, the number of viable cells in each group was determined. In addition, multicycle flow cytometry was performed on all cell lines, and pulsed-field electrophoresis was performed solely on Raji cells to investigate changes in cell cycle patterns and the possibility of DNA fragmentation induced by the magnetic field. A 64 h exposure to the magnetic field produced a reduction in viable cell number in each of the three cell lines. Reductions of 19.04 +/- 7.32%, 22.06 +/- 6.19%, and 40.68 +/- 8.31% were measured for the melanoma, ovarian carcinoma, and lymphoma cell lines, respectively, vs. control groups not exposed to the magnetic field. Multicycle flow cytometry revealed that the cell cycle was largely unaltered. Pulsed-field electrophoresis analysis revealed no increase in DNA breaks related to magnetic field exposure. In conclusion, prolonged exposure to a very strong magnetic field appeared to inhibit the growth of three human tumor cell lines in vitro. The mechanism underlying this effect has not, as yet, been identified, although alteration of cell growth cycle and gross fragmentation of DNA have been excluded as possible contributory factors. Future investigations of this phenomenon may have a significant impact on the future understanding and treatment of cancer.

Carcinoma

Evaluation of ion-implanted-silicon detectors for use in intraoperative positron-sensitive probes.

The continuing development of probes for use with beta (positron and electron) emitting radionuclides may result in more complete excision of tracer-avid tumors. Perhaps one of the most promising radiopharmaceuticals for this task is 18F-labeled-Fluoro-2-Deoxy-D-Glucose (FDG). This positron-emitting agent has been demonstrated to be avidly and rapidly absorbed by many human cancers. We have investigated the use of ion-implanted-silicon detectors in intraoperative positron-sensitive surgical probes for use with FDG. These detectors possess very high positron detection efficiency, while the efficiency for 511 keV photon detection is low. The spatial resolution, as well as positron and annihilation photon detection sensitivity, of an ion-implanted-silicon detector used with 18F was measured at several energy thresholds. In addition, the ability of the device to detect the presence of relatively small amounts of FDG during surgery was evaluated by simulating a surgical field in which some tumor was left intact following lesion excision. The performance of the ion-implanted-silicon detector was compared to the operating characteristics of a positron-sensitive surgical probe which utilizes plastic scintillator. In all areas of performance the ion-implanted-silicon detector proved superior to the plastic scintillator-based probe. At an energy threshold of 14 keV positron sensitivity measured for the ion-implanted-silicon detector was 101.3 cps/kBq, photon sensitivity was 7.4 cps/kBq. In addition, spatial resolution was found to be relatively unaffected by the presence of distant sources of annihilation photon flux. Finally, the detector was demonstrated to be able to localize small amounts of FDG in a simulated tumor bed; indicating that this device has promise as a probe to aid in FDG-guided surgery.

Beta Particles

Stereotactic coordinates from ECT sinograms for radionuclide-guided breast biopsy.

UNLABELLED: Raw data from emission scanners contained in ECT sinograms can provide an abundance of information about the position of an object in the camera's field-of-view. Since some cancers can be detected by PET and SPECT which are not seen clearly on mammograms, CT or other scans, sinogram data could potentially be used to guide tumor biopsy. For example, positron-emitting (18F-labeled Fluoro-deoxyglucose) and single-photon emitting (99mTc-labeled-sestamibi) radiopharmaceuticals have been used successfully to detect many types of breast cancer. By utilizing some relatively simple geometric relationships, a sinogram-based method for biopsy of radiopharmaceutical-avid breast masses guided by data from PET and SPECT scanners has been developed and validated in phantom studies. METHODS: A pair of projection views from a series of sinograms is used to calculate the position of photon-emitting objects. Calculated positions of spheres ranging in size from 1.6 to 3.4 cm diameters containing 18F and 99mTc were compared with measured positions. By adding a single radioactive fiducial marker, emission-guided biopsy of simulated breast lesions was performed with a specially designed phantom containing photon-emitting spheres 12.7 mm in diameter. RESULTS: Correlation between calculated and measured object coordinates were excellent (R = 1.0, R = 1.0 and R = 0.998; x, y and z coordinates, respectively). The maximum error in localization was +/- 3 mm. One hundred percent (10 of 10) of the attempted biopsies of simulated tumors were successful. CONCLUSION: A method for rapidly determining the position of photon-emitting objects in an emission scanner has been developed and tested. This technique, which does not require standard emission or anatomic images, could be used with dedicated biopsy machines or incorporated into "add-on" biopsy devices for existing PET or SPECT cameras.

Biopsy, Needle

Magnetically enhanced protection of bone marrow from beta particles emitted by bone-seeking radionuclides: theory of application.

Utilization of radiopharmaceuticals that directly target radioactivity to tumors for treatment has a great deal of promise. Ideally, lethal doses of radiation could be delivered precisely to areas of disease, while, for the most part, sparing normal tissues. This potential, however, has not yet been fully realized. Current limitations of this approach are low tumor uptake of radiopharmaceuticals and dose-limiting radiotoxicity. In an effort to offset low uptake, radionuclides that emit high average-energy electrons have been proposed. Unfortunately, use of these radionuclides increases myelosuppression on a per decay basis. In order to allow for the utilization of high doses of this class of high-energy beta emitters, we propose the application of a strong static homogeneous magnetic field to constrain the beta particles. Monte Carlo computer simulations indicate that application of a 10 T magnetic field can decrease the total radiation dose from bone-avid tracers to marrow located in shafts of human long bones by 14%. More significantly, however, the penetration depth of high-energy electrons from the bone surface into the marrow can be reduced by up to 74.6%. Preservation of marrow in areas distal to the bone has previously been shown to facilitate relatively rapid recovery from pancytopenia produced by radiation damage to trabecular marrow (without marrow transplantation). Magnetically enhanced protection of bone marrow, therefore, may allow administered doses of high-energy beta-emitting radionuclides to be increased. By raising the limits on injected quantities of such highly ionizing radionuclides, amounts of the radiation dose absorbed by both soft and calcified tissue tumors will be increased, compared to conventional treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Beta Particles

Fluorine-18-fluorodeoxyglucose-guided breast cancer surgery with a positron-sensitive probe: validation in preclinical studies.

UNLABELLED: In this study, the feasibility of utilizing 2-deoxy-2-fluoro-d-glucose (FDG) in conjunction with a positron-sensitive intraoperative probe to guide breast tumor excision was investigated. METHODS: The probe was constructed with a plastic scintillator tip coupled to a photomultiplier tube with fiber optic cable. Anticipated resolution degradation was evaluated by measurement of line spread functions in the presence of background radiation. Realistic photon background distributions were simulated with a human torso phantom and a cardiac insert. The relationship between resolution and energy threshold was measured to find the optimal discriminator settings. In addition, probe sensitivity as a function of energy threshold was determined for various size-simulated tumors. Finally, the ability to localize breast cancers in vivo was tested in a rodent model. Mammary rat tumors implanted in Lewis rats were examined after injection with FDG; these results were correlated with those of histologic analyses. RESULTS: Measurements of line spread functions indicated that resolution could be maximized in a realistic background photon environment by increasing the energy threshold to levels at or above the Compton continuum edge (340 keV). At this setting, the probe's sensitivity was determined to be 58 and 11 cps/muCi for 3.18- and 6.35-mm diameter simulated tumors, respectively. Probe readings correlated well with histologic results: the probe was generally able to discriminate between tumor and normal tissue. CONCLUSION: This study indicates that breast cancer surgery guided by a positron-sensitive probe warrants future evaluation in breast-conserving surgery of patients with breast cancer.

Animals

Modeling of carbon-11-acetate kinetics by simultaneously fitting data from multiple ROIs coupled by common parameters.

UNLABELLED: One of the unique aspects of PET is its ability to noninvasively quantify metabolic processes. Metabolic rate parameters are estimated by fitting the time-activity curves from regions of interest (ROIs) placed on dynamic PET images with a kinetic model. In many cases it is possible to couple these datasets with common parameters, such as the time delay between arrival of tracer in the ROIs and the sampling site. METHODS: Data from eight ROIs placed about images of the myocardium were coupled by the parameters describing the metabolite concentration in the blood. The method was evaluated by comparing estimates of k2 made using the coupled region method and the standard process of fitting data from each region separately. In addition, comparisons were made between estimates of k2 and measured myocardial oxygen consumption. RESULTS: Very little change in mean values of k2 was obtained. The variances, however, were reduced by an average of 37%, compared to the standard method, when the common parameters were not constrained. When the values of the common metabolite parameters were constrained to values previously measured, the average variance in estimates of k2 was reduced by 30%. CONCLUSION: We have demonstrated that the use of this technique can significantly increase the precision of estimates of myocardial oxygen consumption utilizing 11C-acetate PET images. More precise estimates of such quantities can facilitate detection of small regional and/or temporal physiological changes measured with PET. Furthermore, this method can be utilized whenever it is known a priori that one or more kinetic model parameters has the same value for every set of ROI data.

Acetates

A fiber-optically coupled positron-sensitive surgical probe.

UNLABELLED: Positron-emitting radiopharmaceuticals such as 18F-labeled 2-deoxy-D-glucose (FDG) have considerable utility in the noninvasive imaging of cancers due to their rapid and excellent tumor-localizing properties. In addition, the relatively short range of positions in tissue facilitates the precise delineation of FDG-avid tumors. Therefore, FDG used in conjunction with a positron-sensitive probe may be capable of guiding surgical procedures. Many of the current probe systems, however, are sensitive to the intense flux of background photons produced by positron annihilation. We describe the design, manufacture and initial in vitro and in vivo testing of a probe well-suited to the detection of positron-emitting isotopes in a high-photon background. METHODS: The device consists of a small piece of plastic scintillator coupled by fiber-optic cable to a photomultiplier tube. Measurements of resolution and detector sensitivity were obtained. In addition, the reduction in resolution caused by the effects of various levels of background photon flux was determined. RESULTS: These measurements indicate that resolution is degraded minimally (approximately 5% with a background-to-source ratio of 2:1) due to annihilation photon background. Sensitivity for positrons is good, detecting amounts of radioactivity as low as 10.2 nCi of FDG in vitro. In rats given FDG subcutaneously, lymph nodes containing as little as 11 nCi of FDG could be detected above the background activity levels present in normal surrounding tissues. CONCLUSION: A plastic scintillator probe system has been devised which may be highly suitable for intraoperative FDG-guided (or other positron or beta emitting-tracer) surgery.

Animals

Magnetically enhanced radionuclide therapy.

UNLABELLED: Radiopharmaceutical therapy is an increasingly common treatment for cancer. This therapy involves the injection of radiolabeled tumor-specific agents into the patient with subsequent preferential accumulation in the tumor sites. Particulate radiation (usually beta particles) emitted by the radioisotope kill or damage the tumor cells. The effectiveness of radiopharmaceutical therapy, however, is limited by the size of the tumor treated. Energetic particles can easily exist small tumors before they are able to deposit their energy and inflict significant damage. METHODS: We propose the use of a static magnetic field to be applied after the radiopharmaceutical has localized in the tumors, constraining these particles to helical paths. This application would result in substantially confining the emitted particles within the tumor's boundaries, thus increasing radiation dose to the tumor. RESULTS: Computer simulations of radionuclide treatments using 131I, 186Re and 90Y show that a magnetic field of 10 Tesla can increase the radiation dose achieved by conventional radionuclide therapy by up to 71%. In addition, total radiation dose to surrounding normal tissues is substantially reduced. CONCLUSION: Magnetically enhanced radionuclide therapy (MERiT) therefore shows promise as an effective treatment of cancer and warrants further study.

Beta Particles

Sampling requirements for dynamic cardiac PET studies using image-derived input functions.

The utilization of image-derived input functions is becoming common in quantitative PET studies of the heart. Consequently, imaging protocols must be designed to sample both blood and tissue concentrations adequately. Most clinical imaging protocols consist of a series of short initial scans to measure the rapid change in blood and tissue tracer concentration levels, followed by scans of gradually increasing length. The number of initial short scans must be matched to the shape of the input function. In this paper, noise-free simulation studies were performed to evaluate the effect of temporal sampling on estimates of the parameters of a two-compartment kinetic model. In addition, the consequences of varying tracer infusion length and timing were studied. The kinetic model parameters' bias decreased when infusion times were lengthened or sampling rates increased. Our results indicated that tracer infusions of 30 sec were best suited for these studies. Two currently employed clinical imaging protocols were then optimized for use with this infusion scheme. Ten initial scans with durations of 10 sec, or twenty of 5 sec length produced unbiased estimates of kinetic model parameters that describe myocardial physiology. Noisy simulations with the equivalent of one million events confirmed these results.

Heart

A region of interest strategy for minimizing resolution distortions in quantitative myocardial PET studies.

The distortions inherent in PET images of the human heart due to finite image resolution and cardiac motion limit the capability to evaluate physiology quantitatively. A method based on a simple geometrical model of region of interest representations in physical space has been developed to minimize these distortions. In this paper, simulation studies have been performed to evaluate the noise characteristics of the method. This study demonstrates that unbiased estimates of kinetic model parameters which describe myocardial physiology can be measured with an accuracy of 7%-15% for scale-related parameters and 4%-16% for shape-related parameters of kinetic models in studies with the equivalent of 1 million events. Application of the techniques developed in this paper for the measurement of myocardial blood flow in eight dogs (14 independent flow states) shows a strong correlation with microsphere determined blood flow in the same animals (slope = 1.022, intercept = -0.18, r = 0.96).

Animals