Bo-Anders Jönsson

Scintigraphic method to quantify the passage from brain parenchyma to the deep cervical lymph nodes in rats

In order to investigate the kinetics of the passage from the brain parenchyma to the lymphatic system in vivo a high resolution scintillation camera technique was developed. Albumin, albumin colloids and dextran labelled with 99mTc were injected into the right side of the thalamus of anesthetized rats. Continuous measurement of the activity distribution in head and neck were performed for 70 min. Rate constants were calculated by means of a computer program for compartment analysis. The animals were killed 10 h postinjection, to measure the activity in tissue samples. For some animals, images were registered up to 24 h after injection. This work presents an in vivo technique to clarify the particle flow paths in the brain and make quantification possible. The method is simple and does not require continuous blood or lymph sampling. Our work shows that there is a substantial flow of injected material from the brain via lamina cribriformis to the lymphatic system. This route is of great interest for the drainage of the interstitial fluid of the brain. We have also shown a difference in flow for dextran particles with different charge.

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.

An experimental method for in vivo studies of pulmonary platelet sequestration

It has been reorted in earlier in vitro studies that soft tissue trauma and endotoxin-induced shock causes pulmonary platelet trapping (PPT). This paper describes a noninvasive in vivo technique for dynamic studies of PPT in rabbits. Autologous platelets were labeled with111In and reinfused into the animals. The following day, the rabbits were anesthetized and placed in a supine position under a scintillation camera. Continuous measurement of the activity distribution in the animal was performed for 35 min. The first 5 min represented a preshock measurement, whereafter endotoxinE. coli was injected IV. The following 2–3 min showed a sudden increase of radioactivity in the lungs indicating PPT, and thereafter a slow decrease to almost the preshock level. A simultaneous decrease in the number of platelets and the radioactivity in peripheral blood also indicated the induction of PPT. This study clearly shows that PPT can be detected in vivo with an easy, noninvasive scintillation camera method.

Monte Carlo calculations of absorbed doses in tumours using a modified MOBY mouse phantom for pre-clinical dosimetry studies

Abstract Background. Clinical treatment with radionuclides is usually preceded by biokinetic and dosimetry studies in small animals. Evaluation of the therapeutic efficacy is essential and must rely on accurate dosimetry, which in turn must be based on a realistic geometrical model that properly describes the transport of radiation. It is also important to include the source distribution in the dosimetry calculations. Tumours are often implanted subcutaneously in animals, constituting an important additional source of radiation that often is not considered in the dosimetry models. The aims of this study were to calculate S values of the mouse, and determine the absorbed dose contribution to and from subcutaneous tumours inoculated at four different locations. Methods. The Moby computer program generates a three dimensional (3D) voxel-based phantom. Tumours were modelled as half-spheres on the body surface, and the radius was varied to study different tumour masses. The phantoms were used as input for Monte Carlo simulations of absorbed fractions and S factors with the radiation transport code MCNPX 2.6f. Calculations were performed for monoenergetic photons and electrons, and the radionuclides 125I, 131I, 111In, 177Lu and 90Y. Results. Electron energy and tumour size are important for both self- and cross-doses. If the activity is non-uniformly distributed within the body, the position of the tumour must be considered in order to calculate the tumour absorbed dose accurately. If the uptake in the tumour is high compared with that in adjacent organs the absorbed dose contribution to organs from the tumour cannot be neglected. Conclusions. In order to perform accurate tumour dosimetry in mouse models it is necessary to take the additional contribution from the activity distribution within the body of the mouse into account. This may be of significance in the interpretation of radiobiological tumour response in pre-clinical studies.

Thrombogenicity of metallic vascular stents in arteries and veins--an experimental study in pigs

Endovascular expanding metallic stents were percutaneously implanted in the iliac arteries and veins of pigs. The vessels had been stenosed by a ligature of catgut 4 weeks prior to this. Platelets were labeled with Indium 111 and the deposition onto the dilated and stented areas was dynamically registered for 240 min with a scintillation camera. All six arterial and six venous stents remained patent throughout the examination period. At the site of arterial stenting there was an increase, of deposited activity, and in the veins a decrease. These experimental findings support the use of endovascular stents after dilation, especially in venous stenoses.

Early post-traumatic changes in hemodynamics and pulmonary ventilation in alcohol-pretreated pigs

Time relations among trauma, pulmonary and systemic circulation, and lung function were studied in pigs. Eleven animals (b.w. 25-30 kg) were investigated under balanced anesthesia. Ventilation was mechanically controlled. Hemodynamics, pulmonary ventilation, and gas exchange were serially recorded. Seven animals were pretreated with 40% ethanol in saline and four with saline only. Ninety minutes after the ingestion of alcohol or saline, the animals were subjected to a standardized soft-tissue trauma. Cardiac output decreased significantly 2 minutes after trauma and remained low in both groups throughout the observation period of 30 minutes. Pulmonary vascular resistance was significantly increased in the alcohol-pretreated group but was virtually unchanged in the control animals. Systemic vascular resistance was similarly reduced in the two groups. Total compliance was somewhat lower in alcohol-pretreated animals and 10 minutes after the trauma arterial oxygen tension was significantly lower in the alcohol group than in control animals. Carbon dioxide elimination was reduced after trauma in both groups. It is concluded that pulmonary vascular response increased and that total pulmonary compliance is somewhat decreased shortly after trauma in the alcohol group while gas exchange is almost unchanged. The results indicate a negative interaction between alcohol and trauma (Less)

Use of Monte Carlo simulations with a realistic rat phantom for examining the correlation between hematopoietic system response and red marrow absorbed dose in Brown Norway rats undergoing radionuclide therapy with (177)Lu- and (90)Y-BR96 mAbs.

PURPOSE Biokinetic and dosimetry studies in laboratory animals often precede clinical radionuclide therapies in humans. A reliable evaluation of therapeutic efficacy is essential and should be based on accurate dosimetry data from a realistic dosimetry model. The aim of this study was to develop an anatomically realistic dosimetry model for Brown Norway rats to calculate S factors for use in evaluating correlations between absorbed dose and biological effects in a preclinical therapy study. METHODS A realistic rat phantom (Roby) was used, which has some flexibility that allows for a redefinition of organ sizes. The phantom was modified to represent the anatomic geometry of a Brown Norway rat, which was used for Monte Carlo calculations of S factors. Kinetic data for radiolabeled BR96 monoclonal antibodies were used to calculate the absorbed dose. Biological data were gathered from an activity escalation study with (90)Y- and (177)Lu-labeled BR96 monoclonal antibodies, in which blood cell counts and bodyweight were examined up to 2 months follow-up after injection. Reductions in white blood cell and platelet counts and declines in bodyweight were quantified by four methods and compared to the calculated absorbed dose to the bone marrow or the total body. RESULTS A red marrow absorbed dose-dependent effect on hematological parameters was observed, which could be evaluated by a decrease in blood cell counts. The absorbed dose to the bone marrow, corresponding to the maximal tolerable activity that could safely be administered, was determined to 8.3 Gy for (177)Lu and 12.5 Gy for (90)Y. CONCLUSIONS There was a clear correlation between the hematological effects, quantified with some of the studied parameters, and the calculated red marrow absorbed doses. The decline in body weight was stronger correlated to the total body absorbed dose, rather than the red marrow absorbed dose. Finally, when considering a constant activity concentration, the phantom weight, ranging from 225 g to 300 g, appeared to have no substantial effect for the estimated absorbed dose.PURPOSE Biokinetic and dosimetry studies in laboratory animals often precede clinical radionuclide therapies in humans. A reliable evaluation of therapeutic efficacy is essential and should be based on accurate dosimetry data from a realistic dosimetry model. The aim of this study was to develop an anatomically realistic dosimetry model for Brown Norway rats to calculate S factors for use in evaluating correlations between absorbed dose and biological effects in a preclinical therapy study. METHODS A realistic rat phantom (Roby) was used, which has some flexibility that allows for a redefinition of organ sizes. The phantom was modified to represent the anatomic geometry of a Brown Norway rat, which was used for Monte Carlo calculations of S factors. Kinetic data for radiolabeled BR96 monoclonal antibodies were used to calculate the absorbed dose. Biological data were gathered from an activity escalation study with90 Y- and 177 Lu-labeled BR96 monoclonal antibodies, in which blood cell counts and bodyweight were examined up to 2 months follow-up after injection. Reductions in white blood cell and platelet counts and declines in bodyweight were quantified by four methods and compared to the calculated absorbed dose to the bone marrow or the total body. RESULTS A red marrow absorbed dose-dependent effect on hematological parameters was observed, which could be evaluated by a decrease in blood cell counts. The absorbed dose to the bone marrow, corresponding to the maximal tolerable activity that could safely be administered, was determined to 8.3 Gy for177 Lu and 12.5 Gy for 90 Y. CONCLUSIONS There was a clear correlation between the hematological effects, quantified with some of the studied parameters, and the calculated red marrow absorbed doses. The decline in body weight was stronger correlated to the total body absorbed dose, rather than the red marrow absorbed dose. Finally, when considering a constant activity concentration, the phantom weight, ranging from 225 g to 300 g, appeared to have no substantial effect for the estimated absorbed dose.

Cell survival after Auger electron emission from stable intracellular indium exposed to monochromatic synchrotron radiation

The biological effect of Auger electrons emitted from indium in V79 cells was investigated. K-shell vacancies were induced by synchrotron x-rays. Two energies, 100 eV above and below the K-edge of indium, were used. The cell survival for controls was similar to that which has been reported by others, with D37 = 4.4 Gy. Indium-oxine-labelled cells exhibited a survival clearly below that of the controls, D37 = 3.2 Gy, but no significant difference in survival between irradiations above and below the K-edge could be observed. The explanation is, inter alia, that the number of photons interacting with indium atoms incorporated into the cell, is small compared with the number of photons interacting with other atoms in the cell. The toxicity of indium oxine made it impossible to incorporate a sufficient number of indium atoms into the cells to observe a difference in this study. However, monoenergetic irradiation above and below the K-edge, provides a technique for the investigation of basic biological effects of Auger processes.

Early posttraumatic pulmonary platelet trapping and its potentiation by oral pretreatment with alcohol

Soft tissue trauma is associated with platelet aggregation and sequestration in the lungs. This is believed to be an early step in the later development of adult respiratory distress syndrome. In the present experiment using a new method for in vivo dynamic studies of platelet sequestration, we wanted to evaluate the effect of soft tissue trauma on pulmonary platelet trapping in pigs and the influence of acute alcohol intoxication. The results show that significant pulmonary platelet trapping is registered within minutes of trauma and that alcohol significantly increases platelet sequestration in the lungs. This indicates an increased risk for posttraumatic pulmonary problems in alcohol-intoxicated trauma victims.

A Small-Scale Anatomic Model for Testicular Radiation Dosimetry for Radionuclides Localized in the Human Testes

The testis is a radiosensitive tissue. It contains a large number of lobules, which in turn are composed of convoluted seminiferous tubules. The epithelium inside each tubule consists of a complex mosaic of supporting cells and germ cells of different sizes and degrees of maturation. These cells are known to have diverse sensitivity to radiation, those with the highest sensitivity being the spermatogonia, which form part of the basal cell layer, and those with the lowest sensitivity being the mature sperm cells closest to the lumen of the tubule. For many years, the internal dosimetry community has discussed the need for improvements to bring about more detailed, cell-level testicular dosimetry. This paper presents a small-scale dosimetry model for calculation of S factors for several different source–target configurations within the testicular tissue. Methods: A model of the testis was designed in which the lobules were approximated by a cross-section of seminiferous tubules arranged in a hexagonal pattern, with interstitial tissue between them. The seminiferous tubules were divided into concentric layers representing spermatogenic development in the seminiferous epithelium. S factors were calculated for electrons, photons, α-particles, and for 18F, 90Y, 99mTc, 111In, 125I, 131I, 177Lu, and 211At using Monte Carlo simulations. Results: For electrons with low energies the range was small, compared with the diameter of the seminiferous tubules, resulting in high energy deposition close to the source, whereas for higher electron energies more uniform energy deposition was seen, as expected. The same trend was seen for low-energy photons, whose mean free paths are small, compared with the diameter of the seminiferous tubules, resulting in high energy deposition close to the source, whereas for higher photon energies the location of the activity in the testis is less important. Conclusion: The model presented in this paper is a simplification of the organized chaos that constitutes the structure of the actual testis. However, it provides a relevant, small-scale anatomic model to help us understand the significance of the heterogeneity of radioactivity in this important radiosensitive tissue.