Comparison of different cell-cluster models for cell-level dosimetry.

An important factor in dose calculations for targeted radionuclide therapy is the cell-cluster model used. We developed a cell-cluster model based on optimization through mechanical hard-sphere collisions. The geometrical properties and the dosimetric effects of the new model were compared with those of two previous models, i.e. the traditional lattice model and our CellPacker model in which the cells are individually and systematically piled as a cluster. The choice of the cell-cluster model has an effect on the calculated mean absorbed doses in the cells. While CellPacker produces clusters with distinct tumour-healthy tissue interface, our new model is able to make the interface diffuse. Outside the interface the new model is capable to pack cells tighter than CellPacker enabling the description of tissues of higher cellular density. Our two cluster models make it possible to construct the cluster model according to the tissue in question.

Radiation spectra of 111In, 113mIn and 114mIn.

The radiation spectra of 111In, 113In, and 114mIn are calculated with the Monte Carlo computer program IMRDEC. The relaxation probabilities are taken from the EADL file of the Lawrence Livermore National Laboratory. Because this file does not include data for some N and O transitions, these were additionally determined by applying the Kassis rule. Two schemes are applied to calculate the transition energies: 1) a simple (Z + 1)/Z scheme, and 2) accurate calculation solving the relativistic Dirac equations. It is shown that using the extended set of relaxation probabilities leads to generation of many additional low-energy Auger and CK electrons if the (Z + 1)/Z rule is applied. On the other hand, the emissions of almost all these electrons are rejected if their energies are calculated solving the Dirac equations taking into consideration realistic electron vacancies.

Models for estimation of the (10)B concentration after BPA-fructose complex infusion in patients during epithermal neutron irradiation in BNCT.

PURPOSE: To create simple and reliable models for clinical practice for estimating the blood (10)B time-concentration curve after p-boronophenylalanine fructose complex (BPA-F) infusion in patients during neutron irradiation in boron neutron capture therapy (BNCT). METHODS AND MATERIALS: BPA-F (290 mg BPA/kg body weight) was infused i.v. during two hours to 10 glioblastoma multiforme patients. Blood samples were collected during and after the infusion. Compartmental models and bi-exponential function fit were constructed based on the (10)B blood time-concentration curve. The constructed models were tested with data from six additional patients who received various amounts of infused BPA-F and data from one patient who received a one-hour infusion of 170 mg BPA/kg body weight. RESULTS: The resulting open two-compartment model and bi-exponential function estimate the clearance of (10)B after 290 mg BPA/kg body weight infusion from the blood with satisfactory accuracy during the first irradiation field (1 ppm, i.e., 7%). The accuracy of the two models in predicting the clearance of (10)B during the second irradiation field are for two-compartment model 1.0 ppm (8%) and 0.2 ppm (2%) for bi-exponential function. The models predict the average blood (10)B concentration with an increasing accuracy as more data points are available during the treatment. CONCLUSION: By combining the two models, a robust and practical modeling tool is created for the estimation of the (10)B concentration in blood after BPA-F infusion.

Cluster models in cellular level electron dose calculations.

A program for calculating absorbed dose was developed for radioimmunotherapy (RIT) purposes. It was used to determine the difference in the therapeutic effect of (111)In electrons when using a close-packed cubic geometry and a cell cluster model developed in this project. Our cluster model piles the cells individually. The cells were modelled as spheres of diameters of 12 (tumour) and 30 (healthy) microm. Both models were used to generate clusters with spherical tumours inside healthy tissue. The program uses Monte Carlo-based dose kernels. The radiation spectra were calculated from the Auger and x-ray transition strengths and fluorescence yields of (111)In. The results show the importance of the cluster model in cellular level dose calculations. Near the tumour/healthy tissue interface in particular, the doses differ because of geometrical differences. In the case of a small cluster with tumour and total diameters of 30 and 150 microm, the ratio of the therapeutic effects is 20.

The use of TL detectors in dosimetry of systemic radiation therapy.

A method for determining absorbed doses to organs in systemic radiation therapy (SRT) is evaluated. The method, based on thermoluminescent (TL) dosimeters placed on the patient's skin, was validated and justified through a phantom study showing that the difference between measured (TL dosimeters in the phantom) and derived (TL method) values is within 10%. Six radioimmunotherapy (RIT) patients with widespread intraperitoneal pseudomyxoma were also studied. In dose evaluations, special emphasis was on kidneys. In addition to the TL method, the absorbed doses to kidneys were calculated using MIRD formalism and a point dose kernel technique. We conclude that in SRT the described TL method can be used to estimate the absorbed doses to those critical organs near the body surface within 50% (1 SD).

High-accuracy MR tracking of interventional devices: the Overhauser marker enhancement (OMEN) technique.

A new technique for visualization of interventional devices in magnetic resonance imaging is presented. Determination of the position of an invasive device is made possible by incorporating into the device a small marker that emits the NMR signal. This signal is enhanced by the use of the Overhauser phenomenon. This technique differs from the earlier reported techniques for marking interventional instruments in the sense that the contrast between the marker and tissue is not based on different relaxation rates, but on NMR signal enhancement. A prototype marker was constructed and inserted into an inductively fed loop-gap resonator that couples saturation energy with the marker. Circuit analogies are presented that model the Overhauser phenomenon and the coupling circuit. In vitro experiments demonstrated that the marker is visible in MR images up to a slice thickness of 50 mm when inserted in excised animal liver and fat tissues.

Calculating internal dose by convolution from SPECT/MR fusion images.

A new computer program was developed to calculate the absorbed dose. The program is based on the use of the convolution method and abdominal SPECT/MR fusion images. The applicability of the method was demonstrated by using data from (111)In-labeled thrombocyte and 99mTc-labeled colloid studies of three healthy volunteers. Dose distributions in the volunteers and the average absorbed doses in liver and spleen were calculated. The average doses for 99mTc-labeled colloid study were 0.07 +/- 0.02 (liver) and 0.046 +/- 0.005 mGy/MBq (spleen). The results are in good agreement with a Monte Carlo (MC) based method (0.074 for liver and 0.077 mGy/MBq for spleen) used by the International Commission on Radiological Protection (ICRP). For (111)In-labeled thrombocyte study the doses were 0.33 +/- 0.05 (liver) and 8.9 +/- 1.2 mGy/MBq (spleen) versus 0.730 and 7.50, respectively. The differences in dose estimates in the (111)In-labeled thrombocyte study are mainly due to the approximation used in activity quantitation. Convolution of the activity distribution with a point dose kernel is an effective method for calculating absorbed dose distribution in a homogeneous media. Activity distribution must be aligned to anatomical data in order to utilize the calculated dose distribution. The program developed is applicable to and practical for clinical use provided that the input data needed are available.

Kinetics of 111In-labeled bleomycin in patients with brain tumors: compartmental vs. non-compartmental models.

The kinetics of an indium-111 labeled bleomycin complex (111In-BLMC) after rapid intravenous injection in patients with brain tumors was quantified by using compartmental and non-compartmental models. The models were applied to data obtained from 10 glioma, one meningioma, and one adenocarcinoma brain metastasis patients. Blood and urine samples from all the patients and tumor samples from three patients were collected. The mean transit time of 111In-BLMC in the plasma pool was 14 +/- 7 min without and 1.8 +/- 0.6 h when accounting for recirculation, and 13 +/- 4 h in the total body pool. The mean plasma clearance of 111In-BLMC was 0.3 +/- 0.1 m/blood/min and the mean half-life in urine was 3.5 +/- 0.6 h. The mean transfer coefficients for the open three-compartmental model were: excretion from plasma = 0.02 +/- 0.01, from depot to plasma = (12 +/- 9)*10(-4), from plasma to depot = 0.01 +/- 0.01, from tumor to plasma = 0.39 +/- 0.19 and from plasma to tumor = 1.11 +/- 0.57, all in units minute-1. The mean turnover time from the tumor was 4.5 +/- 2.7 min and from the depot 20 +/- 8 h. It is concluded that both compartmental and non-compartmental models are sufficient to describe the kinetics of indium-111 labeled bleomycin complex. The non-compartmental model is more practical and to some extent more efficient in describing the in vivo behaviors of 111In-BLMC than the compartmental model. The compartmental model used provides estimates of both extraction and excretion from the plasma and tumor.

Abdominal SPECT/MRI fusion applied to the study of splenic and hepatic uptake of radiolabeled thrombocytes and colloids.

The importance of applying MRI (CT)/SPECT fusion in the abdominal and thoracic areas has been recognized in recent studies aiming at radionuclide therapy of cancer. According to our earlier results spleen and liver volume determination with different segmentation methods is inaccurate with SPECT alone. We therefore applied a SPECT/MRI registration procedure to the estimation of spleen and liver volumes and spleen/liver activity ratios in three male volunteers administered 111In-labeled thrombocytes and 99mTc-labeled colloids. The objectives of the study were to investigate if the uptake of thrombocytes in the spleen and liver can be measured more accurately when the anatomical borders of these organs are transferred from MRI to SPECT, and to test a SPECT/MRI registration method for improving three-dimensional dosimetry for radiotherapy treatment planning. A good correlation was found between spleen/liver activity ratios calculated from volumetric average activity per pixel values and from total volumetric counts derived from registered data but not from projection data. The average registration residual with this SPECT/MRI fusion method is approximately 1-2 cm in the abdominal area. Combining anatomical images with SPECT is therefore important for improving quantitative SPECT also in the abdomen.

Double-tracer dosimetry of organs in assessment of bone marrow involvement by two monoclonal antibodies.

Five patients with ductal breast cancer were studied using simultaneous administration of 99Tcm-labelled BW250/183 and 131I-labelled B72.3 monoclonal antibodies (MAbs). The distribution and dosimetry of these tracers were evaluated using the information from simultaneous anterior and posterior whole body scintigrams, together with 99Tcm and 131I standard activity sources, recorded on an average of 1, 4, 24, 90 and 224 h after injection. A method to eliminate 131I Scatter on 99Tcm-channel was developed. The geometric means of conjugate views and region-of-interest analysis were used to determine organ uptakes, mean residence times and absorbed radiation dose estimates of organs induced by the tracers. Organ uptakes (% of injected activity/ml) varied from 6.2 x 10(-3 /red marrow to 3.1 X 10(-2)/liver for 99Tcm-MAb and from 3.1 x 10(-2)/red marrow to 1.8 x 10(-1)/liver for 131I-MAb, one hour after injection. Calculated average residence times of organs for 99Tcm-labelled BW250/183 were in the range of physical mean-life of 99Tcm and from 71 to 95 h for 131I-B72.3 respectively. The average total absorbed dose from 99Tcm-MAb to the bone marrow was 0.01 and to the spleen 0.14 mGy/MBq and from 131I-MAb the corresponding values were 0.48 and 10.76 mGy/MBq. This double-tracer technique provides information from two antibodies having different kinetic behaviour and may facilitate in distinguishing various antigens in targeting and control MAb applications.

Analysis of scintigrams by singular value decomposition (SVD) technique.

The singular value decomposition (SVD) method is presented as a potential tool for analyzing gamma camera images. Mathematically image analysis is a study of matrixes as the standard scintigram is a digitized matrix presentation of the recorded photon fluence from radioactivity of the object. Each matrix element (pixel) consists of a number, which equals the detected counts of the object position. The analysis of images can be reduced to the analysis of the singular values of the matrix decomposition. In the present study the clinical usefulness of SVD was tested by analyzing two different kinds of scintigrams: brain images by single photon emission tomography (SPET), and liver and spleen planar images. It is concluded that SVD can be applied to the analysis of gamma camera images, and that it provides an objective method for interpretation of clinically relevant information contained in the images. In image filtering, SVD provides results comparable to conventional filtering. In addition, the study of singular values can be used for semiquantitation of radionuclide images as exemplified by brain SPET studies and liver-spleen planar studies.