| 1. |
- Garkavij, Michael, et al.
(författare)
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Improving radioimmonotargeting of tumors. Variation in the amount of L6 MAb administered, combined with an immunoadsorption system (ECIA)
- 1993
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 32:7-8, s. 853-859
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Ljunggren, Kaj, et al.
(författare)
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Beta camera low activity tumor imaging
- 1993
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 32:7-8, s. 869-872
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
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| 4. |
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| 5. |
- Strand, Sven-Erik, et al.
(författare)
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A general extracorporeal immunoadsorption method to increase tumor-to-tissue ratio
- 1994
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Ingår i: Cancer. - 1097-0142. ; 73:3 Suppl, s. 1033-1037
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Tidskriftsartikel (refereegranskat)abstract
- The idea of applying extracorporeal immunoadsorption (ECIA) in radioimmunodiagnosis and radioimmunotherapy has been proposed previously. The authors here report on the development of new concept using a general method for ECIA based on biotinylated MoAb adsorbed on an avidin column. Athymic rats heterotransplanted with either human melanomas or human lung carcinoma were injected with iodine-125-labeled biotinylated 96.5 or L6 MoAb, respectively. At 24 or 48 hours after the injection, ECIA was performed by pumping blood through a hollow-fiber plasma filter. The separated plasma then was passed through an absorbent (avidin-agarose) column. The whole ECIA procedure lasted for 3 hours. By this ECIA method, the tumor-to-normal tissue ratios were increased in various tissues (i.e., radiosensitive and blood rich organs) by a factor of four to five.
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| 6. |
- Strand, Sven-Erik, et al.
(författare)
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High resolution pinhole SPECT for tumor imaging
- 1993
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 32:7-8, s. 861-867
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Strand, Sven-Erik, et al.
(författare)
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Radioimmunotherapy dosimetry--a review
- 1993
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 32:7-8, s. 807-817
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Forskningsöversikt (refereegranskat)abstract
- 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.
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| 8. |
- Strand, Sven-Erik, et al.
(författare)
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Small animal imaging with pinhole single-photon emission computed tomography
- 1994
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Ingår i: Cancer. - 1097-0142. ; 73:Suppl. 3, s. 981-984
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. High resolution spatial details of the distribution of activity in three dimensions is required to evaluate the localization and dosimetric properties of radiolabelled monoclonal antibodies in tumors and normal tissues. Planar imaging of small animals with a resolution of 5-10 mm is usually the imaging modality of choice. The authors investigated high resolution single-photon emission computed tomographic (SPECT) imaging, based on a rotating pinhole scintillation camera. Although the sensitivity of the pinhole collimator is low, several radionuclides offer suitable decay properties to perform pinhole SPECT, especially in conjunction with high activity levels used in radioimmunotherapy. METHODS. Transverse, sagittal, and coronal sections were reconstructed using a three-dimensional cone-beam algorithm, which is a generalization of the two-dimensional fan-beam filtered backprojection algorithm. Before reconstruction, the pinhole projections were corrected for the decay of the radionuclide, geometric and intrinsic efficiency variations of the camera system, and center of rotation shift. RESULTS. The spatial resolution at 50 mm from the pinhole collimator with 3.3 mm aperture was 3.4 mm, and the sensitivity 7.2 c/s microCi for technetium-99m. With the 2 mm collimator the resolution was 2.2 mm, and the sensitivity was 2.6 c/s/microCi. To show the spatial resolution in vivo, a rat was injected with 185 MBq of technetium-99m-methylene diphosphonate or with 5 mCi technetium-99m-hexamethylpropylene amine oxime. The bone structures were well delineated in the methylene diphosphonate image, and in the hexamethylpropylene amine oxime image, the brain was nicely shown. For comparison a magnetic resonance image for the same section was done. CONCLUSIONS. High resolution SPECT imaging with the pinhole collimator provides mapping of the activity in three-dimensions, needed for more detailed biodistribution data and to perform more accurate dosimetry.
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| 9. |
- Wanying, Q, et al.
(författare)
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Radio-iodinated and internally labelled (35S) IgM monoclonal antibodies in a syngenic rat model
- 1991
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 30:3, s. 379-383
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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