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Biomedical subjects

S E Strand

Publications and source records attributed to S E Strand.

At least 73 records · Page 4Linked to original sources

Radio-iodinated and internally labelled (35S) IgM monoclonal antibodies in a syngenic rat model.

To simulate the human situation concerning human monoclonal antibodies (MAbs), we have introduced a new syngenic rat model with an implanted rat colon carcinoma. Rat IgM MAbs (10B12), labelled by the chloramine-T method with 125I or internally with 35S, were injected intravenously into the rats and the biodistribution was studied for 8 days. The radioactivity uptake in the tumours of the 35S label was higher than that of the 125I label and the retention of 35S in the tumours gave tumour/blood ratios 8 times higher than those of 125I at 48 and 96 h after injection. In this model we have shown that dehalogenation of iodinated IgM MAbs is a serious problem. We therefore suggest that internally labelled MAbs should be used and that further investigations should be carried out in a syngenic rat model, since this probably reflects the clinical situation better than the nude mouse model.

Animals↗

Attenuation and scatter correction in SPECT for sources in a nonhomogeneous object: a monte Carlo study.

Single-photon emission computed tomography (SPECT) is important for imaging radioactivity distributions in vivo. Quantitative SPECT is limited due to attenuation and scatter contribution. Approximations such as constant attenuation and mono-exponential scatter functions will not be valid for non-homogeneous regions. A correction method is described where non-uniform density-maps are used in the attenuation correction. Correction for non-uniform scatter is made by a convolution technique based on scatter line-spread functions (SLSF) calculated for different locations inside a clinically realistic, nonhomogeneous, computer phantom. Calculations have been made for a myocardiac source, a uniform source in the lungs and a tumor located in the lungs. Projections were simulated for photon energies corresponding to 201Tl, 99mTc, and 111In. The results show that quantitative images can be obtained in nonhomogeneous regions. An increased contrast has also been demonstrated in the SLSF-corrected images. Comparison with measurements have been made to validate the Monte Carlo code and the scatter and attenuation method.

Humans↗

Quantitative SPECT by attenuation correction of the projection set using transmission data: evaluation of a method.

A method for measuring attenuation coefficients in single-photon emission tomography (SPECT) is described and evaluated, together with a method for attenuation correction using these measured attenuation coefficients. Build-up, caused by scattered photons, is corrected for by a simple substitution in the algorithms. Transmission studies are performed with a 99mTc- or 57Co flood source, and emission phantom studies with 99mTc line sources. The method is evaluated with variable but well-defined phantoms. The result is accurate attenuation coefficients for different densities, dimensions and geometries, and an accuracy of corrected emission activities of better than +/- 10% in most cases. The present limitations of the method for attenuation correction are discussed.

Algorithms↗

Subcutaneous injection of monoclonal antibody 96.5. Biokinetics in the nude rat heterotransplanted with malignant melanoma.

Nude rats heterotransplanted with human melanoma metastasis were injected subcutaneously on the hind paw with 125I-labelled monoclonal antibody 96.5 and with control antibody 131I-OKT3. The elimination from the injection site followed a biexponential function. The uptake in the inguinal lymph nodes on the side of the injection was initially high, but after 90 h it equalled the control side. The uptake in the tumour was slower than after i.v. injection but higher than in other tissues except blood. More than 80% of the activity in the dissected liver represented circulating blood. The uptake ratio of 96.5/OKT3 was c.3 in the tumours but c. 1 in all other tissues including blood. The capillary filtration coefficient was proportional to the uptake in organs like liver, lungs and muscle. It is concluded that subcutaneously injected radiolabelled monoclonal antibodies are initially transported via the lymph but then mainly distributed via the blood reaching the different tissues including tumours.

Animals↗

Beta camera for static and dynamic imaging of charged-particle emitting radionuclides in biologic samples.

A detection system based on microchannel plates has been constructed to image charged particles emitted by radionuclides in biomedical samples. This technique has significant advantages over conventional film autoradiography for investigating the distribution of radiolabeled compounds: shorter acquisition times due to the high sensitivity, easier sample handling, direct quantification and the ability to perform dynamic studies. The detector performance shows a spatial resolution of 0.9 mm for carbon-14 (14C) (0.156 MeV), good linearity and homogeneity. The noise level is below 50/(cm2.sec). Successful imaging with this system has been performed with beta-emitters 14C, sulfur-35 (35S), iodine-131 (131I), yttrium-90 (90Y), and positron emitters gallium-68 (68Ga), and fluorine-18 (18F). Dynamic studies of axonal transport of 35S-methionine in a nerve, and static images of 90Y-labeled monoclonal antibodies in slices of tumors are presented. The system shows promise for rapid quantitative imaging of charged-particle emitting radionuclides in small biologic samples.

Animals↗

Attenuation correction in SPECT based on transmission studies and Monte Carlo simulations of build-up functions.

The quantitative information in SPECT images is distorted by photon attenuation and contribution of photons scattered in the object. It is, therefore, important to know the distribution of different attenuating tissues in order to be able to perform a proper attenuation correction. A correction method, based on correcting one pixel at a time by using density maps and build-up functions, has been developed. The density map has been produced by transmission measurements of the object using an external, solid 57Co flood source mounted on the scintillation camera head. The outline of the object is accurately defined by the map since the density values outside the object are very close to zero. The build-up of photons scattered in the object has been simulated by a Monte-Carlo code. SPECT-studies with 99mTc, 201T1 and 111In line sources in different parts of a non homogeneous Alderson phantom have been performed. The emission images have been corrected for photon attenuation using the measured density maps and the simulated build-up functions. The results show that quantitative measurements of the radioactivity in nonhomogeneous area can be accomplished to within +/- 10% for different radionuclides by using the attenuation correction described.

Algorithms↗

Scatter and attenuation correction in SPECT using density maps and Monte Carlo simulated scatter functions.

A new scatter and attenuation correction method is presented in which Monte Carlo simulated scatter line-spread functions for different depth and lateral positions are used. A reconstructed emission image is used as an estimate of the source distribution in order to calculate the scatter contribution in the projection data. The scatter contribution is then subtracted from the original projection prior to attenuation correction. The attenuation correction method uses density maps for the attenuation correction of projection data. Simulation studies have been done with a clinically realistic source distribution in cylindrical, homogeneous water phantoms of different sizes and with photon energies corresponding to 201T1, 99mTc, and 111In. The results show excellent quantitative results with an accuracy within +/- 10% for most of the source positions and phantom sizes. It has also been shown that the variation in the event distribution within the source region in the images has been significantly decreased and that an enhancement in the contrast has been achieved.

Humans↗

Autocorrelation spectroscopy for particle sizing and stability tests of radiolabelled colloids.

In many nuclear medicine applications a well defined particle size and stability of administered colloids is of great importance. A fast and reliable sizing technique for routine quality control is therefore essential. This paper evaluates autocorrelation spectroscopy with an instrument capable of analysing several peaks simultaneously. A total of nine 99mTc-labelled colloids and one 99Y-labelled colloid were studied. The autocorrelation spectroscopy measurements were compared with the standard sizing technique of microfiltration. A good agreement between the sizing techniques was found for most of the colloids. The reproducibility of successive measurements was within +/- 12% and +/- 40% when using unimodal analysis and SDP analysis, respectively. Autocorrelation spectroscopy was found to be well suited for particle sizing and stability tests of radiolabelled colloids.

Colloids↗

Evaluation in vitro and in vivo of two labelling techniques of different 99mTc-dextrans for lymphoscintigraphy.

Five dextrans with different molecular weights and charges were labelled with 99mTc. The labelling methods presented by Henze et al. (1982a) and Ercan et al. (1985) were compared. The labelling efficiency was tested with gel column chromatography scanning (GCS), gel chromatography (GC) combined with the Anthrone test, paper chromatography (PC) and thin layer chromatography (TLC). The GCS technique always indicated a lower labelling efficiency than the PC and TLC techniques, which was due to a more optimal separation of the radioactive components. Gel chromatography in combination with the Anthrone test made it easy to identify the different radiochemical components in contrast to the other methods. Dextran solutions were injected subcutaneously bilaterally at the xiphoid processes in rabbits. The injection sites were massaged for 30 s. Uptake in the parasternal lymph nodes was registrated with a scintillation camera. The animals were killed and dissected at the end of the study. This investigation shows that the labelling method of Ercan et al. gives the highest labelling efficiency. Furthermore, the final pH (4.5) for the dextran solution makes it more useful for injection. For quality control of 99mTc-labelled dextran we recommend the Anthrone test as a complement to GC because it is a quick and simple method of determining the dextran content.

Animals↗

A Monte Carlo program for the simulation of scintillation camera characteristics.

There is a need for mathematical modelling for the evaluation of important parameters for photon imaging systems. A Monte Carlo program which simulates medical imaging nuclear detectors has been developed. Different materials can be chosen for the detector, a cover and a phantom. Cylindrical, spherical, rectangular and more complex phantom and source shapes can be simulated. Photoelectric, incoherent, coherent interactions and pair production are simulated. Different detector parameters, e.g. the energy pulse-height distribution and pulse pile-up due to finite decay time of the scintillation light emission, can be calculated. An energy resolution of the system is simulated by convolving the energy imparted with an energy-dependent Gaussian function. An image matrix of the centroid of the events in the detector can be simulated. Simulation of different collimators permits studies of spatial resolution and sensitivity. Comparisons of our results with experimental data and other published results have shown good agreement. The usefulness of the Monte Carlo code for the accurately simulation of important parameters in scintillation camera systems, stationary as well as SPECT (single-photon emission computed tomography) systems, has been demonstrated.

Computer Simulation↗

Organ sequestration of 65Zn during experimental sepsis.

Alteration in the metabolism of zinc during infections has been reported. We have studied the redistribution of endogenous zinc by making the animals physiologically stable by daily intra-gastric administration of 65Zn prior to the induction of sepsis. Organ uptake of exogenous zinc was studied by investigating the organ uptake of 65Zn after an intravenous injection during sepsis. Male Sprague-Dawley rats, were kept in metabolic cages to monitor the excretion of the radioisotope. They were made septic using a gelatine capsule containing E. coli, Bacteroides fragilis in a standardised mixture with sterile rat faeces and barium sulphate, implanted into the abdomen. The plasma radioactivity in the septic state was significantly lower when compared to control rats. In the septic state, there was an increased uptake of endogenous zinc after oral administration of radioactive zinc in the liver, pancreas, large intestine and testes. When administered intravenously in septic animals we found a decreased uptake of exogenous zinc in the pancreas, large intestine, small intestine, bone and testes. Thus the distribution of endogenous and exogenous zinc seems to differ during the septic state.

Journal Article↗

Radiolabeled colloids and macromolecules in the lymphatic system.

The scintigraphic technique to investigate the lymphatic system is based on a good knowledge of basic criteria in order to correctly interpret the findings. This article penetrates these criteria, updates the present knowledge, and covers basic science work and clinical applications. The anatomy, physiology, and pathology of the lymphatic system are covered. Basic criteria for the radiopharmaceuticals to be used are described as well as their quality control. The principles for lymphoscintigraphy are described. The dosimetry in lymphoscintigraphy as well as radiation risk is estimated for different procedures. Experimental animal studies are summarized. Clinical applications cover staging procedures for breast cancer, malignant melanoma, pelvic neoplasms, and lymphoma. Lymphadenoectomy follow-up studies are also included. The use of lymphoscintigraphy in radiotherapy dose planning is described as well as lymphatic function studies in, e.g., edema and lymph transplantations.

Colloids↗

Biokinetics of radiolabeled monoclonal antibodies in heterotransplanted nude rats: evaluation of corrected specific tissue uptake.

A tumor model is presented to study the biokinetics and localization of radiolabeled monoclonal antibodies (MAb) in the nude rat (Rowett RNu/RNu) heterotransplanted with human melanoma metastases. The nude rat is larger, less sensitive, and lives longer than the nude mouse. It is, therefore, well suited for in vivo studies of tumor localization with radiolabeled monoclonal antibodies. The tumor-to-host weight ratio was closer to the human situation for the nude rat than for the mouse, and quantitative imaging could be performed with a parallel hole collimator. We followed the antibody biokinetics for as long as 8 days, with repeated blood sampling and imaging. Specific uptake of MAb was higher in tumor tissue than in all other tissues except blood. Initial high uptake was also recorded in the bone marrow. The lymph glands showed a slow uptake of specific and control antibody. A simple in vitro correction procedure is described to calculate the corrected specific tissue uptake (STUcorr) that takes the blood activity into account. Thus it was shown that 80% of the tissue uptake in the dissected liver at 30 hr was due to labeled antibodies circulating in the blood. The specific tissue uptake ratio of antibodies 96.5 and OKT3 (nonspecific control) was unity for all other organs except for tumor tissue, where the ratio was greater than two and even higher when correction for blood content of labeled antibody was made.

Animals↗

Platelet aggregation on peritoneal tube grafts and double velour grafts in the inferior vena cava of the pig.

In 14 pigs the infrarenal vena cava was replaced with a peritoneal tube graft or a collagen-coated double velour graft. With 111In-labelled platelets dynamic in vivo imaging of platelet aggregation over the graft was carried out using a scintillation camera. After removal, the grafts were examined by autoradiography for an evaluation of the platelet aggregation pattern. Measurements of activity in different regions of the grafts were also performed. The results indicated low activity uptakes both in vivo and in vitro. The dynamic study did not show any uniform increase of activity content 1-3 h postoperatively, in any of the groups. During the period 2-3 h postoperatively no increasing activity accumulation was found. Hemashield Microvel grafts had an uptake of 0.19 per cent of the total activity while the corresponding figure for peritoneal tube grafts was 0.17 per cent. The activity distribution on different parts of the grafts indicated lower accumulation on the Hemashield graft surfaces than in the anastomoses, while the accumulation was higher on the graft surface of peritoneal tube grafts. The autoradiographical findings supported this indication. In conclusion, low platelet aggregation was found with both dynamic in vivo imaging and in vitro activity measurements on both peritoneal tube grafts and collagen-coated double velour grafts.

Animals↗

Dose planning with SPECT.

In nuclear medicine imaging, single photon emission computed tomography (SPECT) is used with increasing frequency for studies of different organs. A new approach is to use quantitative SPECT for dose planning in radionuclide therapy. Important parameters to estimate dose planning are described here.

Humans↗

Biokinetics and dosimetry for 195Au, evaluated in an animal model.

The use of the generator produced radionuclide 195mAu, half life 30 s, has become feasible for several different investigations, e.g. cardiac studies. To assess the absorbed dose from the long lived radionuclide 195Au (the daughter of 195mAu, half life 183 days), a biodistribution study of 195Au was performed in animals. Seven rabbits were injected with eluate from a 195mHg-195mAu generator and the retention and the biodistribution of the long lived gold isotope was investigated. The activity was localized mainly in the liver and the kidneys. Transforming the data to man resulted in an absorbed dose from 195Au from 1 elution (approximately 925 MBq 195mAu) of 2.2 mGy to the kidney and 1.3 mGy to the liver and an effective dose equivalent of 0.26 mSv. The total effective dose equivalent from all radionuclides in the eluate (195mAu, 195Au, 195mHg and 195Hg), was estimated to be 0.65 mSv for a single injection (925 MBq 195mAu).

Animals↗

Oxygen and nitrate reduction kinetics of a nonflocculating strain of Zoogloea ramigera.

The oxygen and nitrate reduction kinetics of a nonflocculating strain of Zoogloea ramigera were determined. Axenic, nitrate-reducing bacterial suspensions were acclimated to various oxygen levels in a chemostat while measuring nitrate reduction in the presence of high ammonium nitrogen concentrations. Significant nitrate reduction was observed at oxygen concentrations up to 8 mg L-1. Oxygen consumption was inhibited by oxygen concentrations in excess of 2 mg L-1.

Bacteriological Techniques↗