Biomedical subjects

S E Strand

Publications and source records attributed to S E Strand.

At least 55 records · Page 3Linked to original sources

PubMed1994

3D reconstruction for a multi-ring PET scanner by single-slice rebinning and axial deconvolution.

A three-dimensional (3D) image reconstruction method, which was originally developed for a positron emission tomography (PET) system consisting of two rotating scintillation cameras, has now been implemented for a multi-ring PET scanner with retractable septa. The method is called 'single-slice rebinning with axial deconvolution' (SSAD), and can be described as follows. The projection data are sorted into transaxial 2D sinograms. Correction for the axial blurring is made by deconvolution in the sinograms. To obtain the axial spread functions, which depend on the activity distribution, 2D reconstruction is first made using a limited axial acceptance angle. The final 3D image is obtained by 2D reconstruction of transaxial planes. The method is simple but not approximate, has a modest memory requirement, and can be combined with different 2D techniques. Evaluations by Monte Carlo simulations and phantom studies have been made.

Algorithms↗

PubMed1994

Relative biological effectiveness of 99mTc radiopharmaceuticals.

The radiotoxicity of three 99mTc-labeled compounds is investigated using spermatogenesis in mouse testis as the experimental model, and spermatogonial cell survival as the biological end point. The radiopharmaceuticals studied are pertechnetate (99mTcO4-), pyrophosphate (99mTc-PYP), and hydroxyethylene diphosphate (99mTc-HDP). The mean lethal doses at 37% survival (D37) are 0.70 +/- 0.06, 0.84 +/- 0.13, and 0.59 +/- 0.08 Gy for 99mTcO4-, 99mTc-PYP, and 99mTc-HDP, respectively. When these results are compared with the D37 value obtained with external x rays or internal gamma rays, the relative biological effectiveness (RBE) of these compounds are 0.94 +/- 0.09, 0.79 +/- 0.13, and 1.1 +/- 0.16, respectively. These results show that the radiotoxicity of 99mTc in mouse testis is essentially similar to that of low-LET radiations (i.e., RBE approximately 1). To understand these results, the distribution of these radiocompounds in the testis is determined and correlated with the observed RBE values. The expected range of RBE values for 99mTc radiopharmaceuticals in organs is 0.95 to 1.5, depending on the fraction of organ activity that is bound to DNA. This suggests that the Auger electrons emitted in the decay of 99mTc are not capable of causing extreme toxicity in vivo. These results provide further support for 99mTc as the radionuclide of choice for imaging in nuclear medicine.

Animals↗

PubMed1994

Improving radioimmunotargeting of tumors: the impact of preloading unlabeled L6 monoclonal antibody on the biodistribution of 125I-L6 in rats.

In the radioimmunotherapy of malignancies the uptake of monoclonal antibodies (MoAb) is commonly low in tumors compared with normal tissue. Several methods have been suggested to increase the tumor-to-normal tissue (T/N) ratio. In this study we have investigated the biodistribution of different amounts of 125I-L6-biotin MoAb in combination with a preload of unlabeled L6 MoAb. Nude rats were injected with 50 micrograms or 250 micrograms of unlabeled L6 24 hours prior to the injection of 10 micrograms, 50 micrograms or 250 micrograms of 125I-L6, antipancarcinoma MoAb. Dissections were performed 24 hours after the injection of radiolabeled MoAb. The maximal enhancement of tumor uptake with simultaneously decreased uptake in normal tissues was with 250 micrograms of 125I-L6 preceded by a preload of 50 micrograms unlabeled L6. Mean T/N ratios were improved by a factor of 2.9 for bone marrow, 3.4 for liver, 3.7 for lungs and 2.3 for kidneys as compared with the corresponding controls. This study demonstrated that preinjection of optimal amounts of unlabeled L6 MoAb may increase the uptake of 125I-L6 by tumor and improve the T/N ratios. Based on present data, preloading with unlabeled MoAb should be considered in future clinical studies with immunoconjugates to improve the radioimmunotargeting of tumors. It is essential to titrate an appropriate amount of the preload, thus avoiding possible tumor antigen saturation of unlabeled MoAbs but simultaneously decreasing the uptake of subsequently injected radiolabeled MoAb in normal tissues.

Animals↗

PubMed1994

Comparison of four scatter correction methods using Monte Carlo simulated source distributions.

UNLABELLED: Scatter correction in SPECT is important for improving image quality, boundary detection and the quantification of activity in different regions. This paper presents a comparison of four scatter correction methods, three using more than one energy window and one convolution-subtraction correction method using spatial variant scatter line-spread functions. METHODS: The comparison is based on Monte Carlo simulated data for point sources on- and off-axis, hot and cold spheres of different diameters, and a clinically realistic source distribution simulating brain imaging. All studies were made for a uniform cylindrical water phantom. Since the nature of the detected photon is known with Monte Carlo simulation, separate images of primary and scattered photons can be recorded. These can then be compared with estimated scatter and primary images obtained from the different scatter correction methods. The criteria for comparison were the normalized mean square error, scatter fraction, % recovery and image contrast. RESULTS: All correction methods significantly improved image quality and quantification compared to those obtained with no correction. Quantitatively, no single method was observed to be the best by all criteria for all the source distributions. Three of the methods were observed to perform the best by at least one of the criteria for one of the source distributions. For brain imaging, the differences between all the methods were much less than the difference between them and no correction at all. CONCLUSION: It is concluded that performing scatter correction is essential for accurate quantification, and that all four methods yield a good, but not perfect, scatter correction. Since it is hard to distinguish the methods consistently in terms of their performance, it may be that the choice should be made on the basis of ease of implementation.

Brain↗

PubMed1994

Pinhole SPECT: an approach to in vivo high resolution SPECT imaging in small laboratory animals.

UNLABELLED: The performance of pinhole SPECT and the application of this technology to investigate the localization properties of radiopharmaceuticals in vivo in small laboratory animals are presented. METHODS: System sensitivity and spatial resolution measurements of a rotating scintillation camera system are made for a low-energy pinhole collimator equipped with 1.0-, 2.0- and 3.3-mm aperture pinhole inserts. The spatial detail offered by pinhole SPECT for in vivo imaging was investigated in studies of the brain and heart in Fisher 344 rats by administering 201TICI, 99mTc-HMPAO, 99mTc-DTPA and 99mTc-MIBI. Image acquisition is performed using a rotating scintillation camera equipped with a pinhole collimator; projection data are acquired in conventional step-and-shoot mode as the camera is rotated 360 degrees around the subject. Pinhole SPECT images are reconstructed using a modified cone-beam algorithm developed from a two-dimensional fanbeam filtered backprojection algorithm. RESULTS: The reconstructed transaxial resolution of 2.8 mm FWHM and system sensitivity of 0.086 c/s/kBq with the 2.0-mm pinhole collimator aperture provide excellent spatial detail and adequate sensitivity for imaging the regional uptake of the radiopharmaceuticals in tumor, organs and other tissues in small laboratory animals. CONCLUSION: The resolution properties of pinhole SPECT are superior to those which have been achieved thus far with conventional SPECT or PET imaging technologies. Pinhole SPECT provides an important approach for investigating localization properties of radiopharmaceuticals in vivo.

Animals↗

PubMed1993

Electron microscopy and computed microtomography studies of in vivo implanted mini-TL dosimeters.

The need for direct methods of measuring the absorbed dose in vivo increases for systemic radiation therapy, and in more sophisticated methodologies developed for radioimmunotherapy. One method suggested is the use of mini-thermoluminescent dosimeters (TLD). Recent reports indicate a marked loss of signal when the dosimeters are used in vivo. We investigated the exterior surface of the dosimeters with scanning electron microscopy and the interior dosimeter volume with computed microtomography. The results show that the dosimeters initially have crystals uniformly embedded in the teflon matrix, with some of them directly exposed to the environment. After incubation in gel, holes appear in the dosimeter matrix where the crystals should have been. The computed microtomographic images show that crystals remain in the interior of the matrix, producing the remaining signal. We conclude that these dosimeters should be very carefully handled, and for practical use of mini-TLDs in vivo the dosimeters should be calibrated in equivalent milieus. An alternative solution to the problem of decreased TL efficiency, would be to coat the dosimeters with a thin layer, of Teflon, or other suitable material.

Animals↗

PubMed1993

Radioimmunotherapy with 90Y-labeled monoclonal antibodies in a nude mouse ovarian cancer model.

Tumor stroma contains much fibrin, and so monoclonal antifibrin antibody can accumulate in tumors. We treated nude mice bearing human ovarian carcinoma xenografts with 90Y-labeled monoclonal antifibrin antibody Fab fragments administered intratumorally. The survival time vs. a control group was significantly prolonged and tumor growth rate was decreased. Another group of animals was treated with 90Y-labeled OC 125-monoclonal antibody; these mice received the antibodies intratumorally, intraperitoneally or intravenously. The survival time was longest in the intratumorally treated group. There was no significant difference in survival between 90Y-labeled OC 125 and antifibrin in the intratumorally treated animal groups. The tissue activity distribution studies revealed that bone marrow is the critical organ. Intratumorally injected monoclonal 90Y-antifibrin antibodies were retained at least 36 h (up to 50% of injected activity per gram tumor tissue) in the xenograft after one treatment, causing cell death. Beta-camera imaging and immunohistochemistry were performed for studies of the correlation between 90Y activity and fibrin distribution in tumor specimens. These results were in concordance. In conclusion, intratumoral administration seems suitable for radioimmunotherapy, with an antibody that targets stromal structures. The accumulation can be successfully monitored by a beta-camera.

Animals↗

PubMed1993

Radioimmunotherapy dosimetry--a review.

Results from therapeutic trials in systemic radiation therapy with radiolabelled monoclonal antibodies are difficult to compare, because of lack of accurate dosimetry. This applies macroscopically as well as microscopically for both tumours and normal tissues. For treatment planning in radioimmunotherapy both the macroscopic and the microscopic absorbed dose distribution must be known. The former is based on a proper knowledge of parameters, such as activity quantitation techniques in both planar and SPECT imaging, different correction techniques, and high activity measurements. Absorbed dose calculations and treatment planning techniques are based on analytical or Monte Carlo calculations. The PET technique with higher resolution is also suggested for radioimmunotherapy planning. Accurate in vivo absorbed dose measurement techniques to verify the calculated absorbed doses are needed in treatment planning. Monitoring the absorbed rate is desirable to assess radiobiological effect. Several ways of enhancing the therapeutic ratio are suggested, especially novel technique with extracorporeal immunoadsorption. An important topic is small scale dosimetry, which is based on techniques for detailed imaging of activity distributions to calculate the absorbed dose distribution.

Adsorption↗

PubMed1993

Improving radioimmonotargeting of tumors. Variation in the amount of L6 MAb administered, combined with an immunoadsorption system (ECIA).

Extracorporeal immunoadsorption (ECIA) is a new method for the selective removal of circulating radiolabeled monoclonal antibodies (MAb) from plasma to increase the uptake in tumor versus normal tissues (T/N-ratio). To ascertain whether the amount of MAb affects T/N ratios immediately and 24 h after ECIA, we used a rat model with two tumor sites--one intramuscular (im) and one below the subrenal capsule (SR). Extracorporeal immunoadsorption was done with an avidin-agarose column after injection of 125I-labeled biotinylated L6 MAb. The animals received 10, 50 or 250 micrograms of L6 only (controls), or followed by ECIA. The efficacy of the procedure in removing plasma activity was 80-95%. For both tumor sites, the highest T/N-ratios were obtained with 10 micrograms L6. All T/N-ratios significantly improved for SR tumors by a factor ranging from 3.2 (lung) to 12.6 (bone marrow). The T/N-ratios were still elevated 24 h after ECIA. Injection of larger amounts of MAb, probably causing a higher degree of tumor saturation, will not necessarily improve the T/N ratio after ECIA.

Adenocarcinoma↗

PubMed1993

High resolution pinhole SPECT for tumor imaging.

High-resolution, non-invasive, 3D-imaging techniques would greatly benefit the investigation of the localization properties of tumor-specific radiopharmaceuticals in laboratory animals. The present study reports how pinhole SPECT can be applied to tumor localization studies in small laboratory animals to provide high resolution SPECT images in vivo. Pinhole SPECT was performed using a rotating scintillation camera, equipped with a pinhole collimator. The sensitivity of a 2 mm diameter collimator at 45 mm from the source is 90 cps/MBq for 99mTc. The planar spatial resolution at a 45 mm distance is 2.2 mm. The transaxial spatial resolution, with a distance of 45 mm between the collimator aperture and the axis of rotation, is 3.1 mm. For SPECT imaging, spatial linearity is preserved across the usable field-of-view. The major advantage of the high resolution properties of pinhole tomography is demonstrated by the enhanced lesion-to-normal-brain uptake ratio achieved on tomographic slices as compared to planar images. For example, 201Tl tumor-to-normal-brain uptake ratios of 1.1 to 1.3 observed on planar images, corresponded to ratios ranging from 3.2 to 3.7 on the SPECT slices. Examples of the activity distributions of two radiopharmaceuticals in tumor and in normal brain for sagittal and coronal images are given. In all cases, tumors are clearly delineated on the pinhole SPECT slices. The present study shows that pinhole SPECT performed with standard SPECT instrumentation can give high spatial resolution images, with a FWHM approximately 3 mm and a sensitivity approximately 100 cps/MBq for 99mTc.

Animals↗

PubMed1993

Beta camera low activity tumor imaging.

A new technique, the beta camera, to complement film autoradiography, with fast quantitative imaging of beta particle-emitting radionuclides has been developed. It consists of a thin plastic scintillator and a light-sensitive microchannel plate detector. The thin tissue sample is mounted on the scintillator. Our first system had a high background and a moderate spatial resolution of 900 microns. We now report an improved system with a photomultiplier tube mounted on the scintillator of the microchannel plate detector. Only events registered by both detectors are accepted. A fast coincidence unit processes the signals, and if a time overlap exists, an event is generated in the beta camera. In the coincidence mode, images with low activity distribution of 201Tl (count rate 1 s-1) in 50 microns-thick slices of a human glioma tumor could be recorded with a spatial resolution of 500 microns.

Brain Neoplasms↗

PubMed1993

A general, extracorporeal immunoadsorption method to increase the tumor-to-normal tissue ratio in radioimmunoimaging and radioimmunotherapy.

The aim of this study was to investigate a new extracorporeal immunoadsorption method to improve tumor-to-normal tissue ratios in radioimmunoimaging (RII) and radioimmunotherapy (RIT). We have developed and investigated a general method using biotinylated antibodies and an agarose-avidin column for extracorporeal immunoadsorption. The studies were made in an animal model and extracorporeal immunoadsorption (ECIA) was performed 24 or 48 hr after the injection of 125I-labeled biotinylated antibodies. In athymic rats, heterotransplanted with human malignant melanoma, 90%-95% of the circulating activity was removed with ECIA. The tumor-to-normal tissue ratios at 24 hr was increased 4 times (from 1.2 to 5.1) in the liver, 2.5 times (0.7 to 1.8) in the lung, 4 times (1 to 4) in the kidneys and 4 times (1.4 to 5) in the bone marrow. Whole body activity was reduced by 40%-50%. Tumor-to-organ ratios at 48 hr were increased 3.5 times (from 1.5 to 5.2) in the liver, 2 times (0.9 to 1.7) in the lung, 3 times (1.3 to 3.8) in the kidneys and 4 times (1.4 to 5.5) in the bone marrow. Whole body activity was reduced by 35% when ECIA was performed 48 hr after injection. This study proves that an important reduction in background activity, and thereby an improvement in the tumor-to-background ratio, can be achieved by using this generally applicable, biotin-avidin ECIA method. For RII, the improved ratio increases the possibilities of detecting tumors and metastases in blood-rich organs. For RIT, the procedure may lead to a decreased absorbed dose to bone marrow and other critical organs.

Animals↗

PubMed1992

Quantitative single photon emission tomography: verification for sources in an elliptical water phantom.

Accurate absorbed dose calculations are important for a proper dose planning in internal radionuclide therapy. The activity distribution must be measured and the target volume defined. This can be done with single photon emission tomography (SPET) if proper attenuation and scatter correction are employed. This study investigated the calculation of the activity and the volume of different spherical sources. These two parameters are essential for a proper dose calculation. The scatter and attenuation correction method is based on spatially variant scatter functions and density maps. The volume calculation method is based on obtaining a threshold from a grey-level histogram. Both point sources and spheres of different diameters containing technetium-99m were placed in different locations in an elliptical water phantom and imaged by SPET. The activity and the volume of the spheres were calculated from the SPET images and compared with known activities. Results show a quantification of activity within 10% for most of the sources. Important influences on the quantification are (a) the presence of artefacts due to improper reconstruction and (b) the finite spatial resolution which affects the total number of counts within the determined volume.

Humans↗

PubMed1992

A PET system based on 2-18FDG production with a low energy electrostatic proton accelerator and a dual headed PET scanner.

We have developed a comparatively inexpensive PET system, based on a rotating scanner with two scintillation camera heads, and a nearby low energy electrostatic proton accelerator for production of short-lived radionuclides. Using a 6 MeV proton beam of 5 microA, and by optimization of the target geometry for the 18O(p,n)18F reaction, 750 MBq of 2-18FDG can be obtained. The PET scanner shows a spatial resolution of 6 mm (FWHM) and a sensitivity of 80 s-1kBq-1ml-1 (3 kcps/microCi/ml). Various corrections are included in the imaging process, to compensate for spatial and temporal response variations in the detector system. Both filtered backprojection and iterative reconstruction methods are employed. Clinical studies have been performed with acquisition times of 30-40 min. The system will be used for clinical experimental research with short- as well as long-lived positron emitters. Also the possibility of true 3D reconstruction is under evaluation.

Astrocytoma↗

PubMed1992

A quantitative autoradiographic study of the heterogeneous activity distribution of different indium-111-labeled radiopharmaceuticals in rat tissues.

In light of the increased interest in small scale dosimetry, this paper presents a quantitative autoradiographic method for evaluation of heterogeneous activity distribution in tissues. This was studied in rat tissues after administration of 111In-chloride, -oxine, -tropolone, 111In-labeled homologous blood cells and 111In-anti-CEA-F(ab')2, using quantitative whole-body autoradiography. Quantification was performed utilizing an image analyzing system designed for whole-body autoradiographs. Very heterogeneous activity distribution was found in several tissues including the liver, spleen, kidneys, bone marrow, lymph nodes and testes. Notable was the high 111In uptake in organs characterized as rapidly proliferating, and known to have numerous transferrin receptors. In the gastrointestinal tract, all activity was associated with the intestinal walls. The heterogeneous tissue distribution shown in this investigation accentuates the necessity for performing detailed studies of the tissue distribution of radiopharmaceuticals. This is especially important for the radiation dosimetry of radionuclides emitting beta-particles or low energy electrons. We suggest whole-body autoradiography as an excellent implement to determine local activity concentrations in organs and tissues necessary for accurate absorbed dose calculations.

Animals↗

PubMed1992

Radiation dosimetry for indium-111-labeled anti-CEA-F(ab')2 fragments evaluated from tissue distribution in rats.

Accurate dosimetric investigations are important to be able to fulfill the ambition of radiation protection in nuclear medicine and to minimize the radiation burden to the patient. This paper presents human radiation absorbed dose estimates following an administration of an 111In-labeled anti-CEA-F(ab')2 (BW431/31) based on detailed biodistribution and elimination data in a rat model. Animals were followed from the time of injection up to 28 days after injection. A significant initial uptake of 111In in the bone marrow, 25% of injected activity, was evident after 6 hr. The kidneys showed a maximal uptake of 20% at 24 hr. At the end of the study, 27% of the activity was still retained in the whole body. The estimated humans absorbed dose to the kidneys, testes, spleen and bone marrow was 2.27, 0.80, 0.51 and 0.37 mGy MBq-1, respectively. The effective dose was estimated to 0.27 mSv MBq-1. The tissue distribution in rats was comparable to that in humans, which was confirmed by whole-body scintigrams and human biopsies.

Animals↗

PubMed1991

A new method for quantification of image distortion due to pile-up in scintillation cameras.

Characterization of the count-rate performance of scintillation cameras should include not only the specification of count losses. At high count rates, there is also an image distortion due to the mispositioning of pile-up events. In this paper a simple and clinically relevant procedure to quantify this distortion is presented. The images of a square uniform technetium-99m phantom at high and low count rates are used. The fraction of the total counts being correctly positioned is determined as the peripheral count density divided by the total average count density. This ratio, corrected for the camera non-uniformity at low count rates, is called the 'positioning ability'. According to the National Electrical Manufacturers' Association (NEMA), the 'system count rate performance with scatter' should be reported as the measured count rate giving 20% count losses. In this paper it is suggested that this measure be complemented by a measure of the fraction correct positioned events at this count rate. This fraction, the 'high count rate positioning ability', can be easily and accurately measured using our method. The method has been tested on two different scintillation cameras. For one of them the high count rate positioning ability was determined as 91% at a measured count rate of 30,000 s-1 with 20% count losses. For the other camera, the corresponding figures were 88% at 59,000 s-1 and close to 100% at 38,000 s-1, before and after the installation of a new pile-up rejection circuit, respectively.

Gamma Cameras↗

PubMed1991

Tumour uptake of monoclonal antibody after regional intraarterial injection. Biokinetics in the nude rat heterotransplanted with malignant melanoma.

Nude rats were heterotransplanted with human melanoma metastases on both thighs. Ten days later a bolus of 125I-labelled monoclonal antibody (MAb) 96.5 was injected through a catheter in the common femoral artery. The femoral vein was clamped for 15 min to obstruct the venous outflow from the injected leg. The specific tissue uptake (%/g) in the tumour on the injected side compared to the non-injected side showed initially higher uptake (ratio 7.2 at 3 h). After 24 h there were no side differences. The tumour to muscle ratio was 2.8 at 3 h when injected and control sides were compared. Intravenous or subcutaneous injection gave similar specific tissue uptake as regional arterial injection after 24 h. Tissue to plasma ratios were similar after intravenous and subcutaneous injection of monoclonal antibodies. Intraarterial injection of a bolus of labelled monoclonal antibodies and obstructing the venous outflow thus increased the tumour uptake during a short period of time during which the contrast enhancement was three-fold.

Animals↗