Biomedical subjects

S E Strand

Publications and source records attributed to S E Strand.

At least 37 records · Page 2Linked to original sources

PubMed1997

Extracorporeal whole-blood immunoadsorption enhances radioimmunotargeting of iodine-125-labeled BR96-biotin monoclonal antibody.

UNLABELLED: This study investigates the efficacy of tumor radioimmunotargeting with 125I-labeled BR96-biotin monoclonal antibody using a new method, whole-blood immunoadsorption (WBIA), based on direct adsorption of unbound monoclonal antibody (MAb) from blood without preceding separation of plasma. METHODS: Highly tumor-reactive, internalizing, chimeric BR96 MAb of isotype IgG1 binds to a tumor-associated Lewis-type (Le(Y)) cell surface antigen. Forty-six Brown Norwegian male rats were inoculated intramuscularly and beneath the liver or kidney capsule with syngeneic rat colon carcinoma BN7005, expressing Lewis-type antigen, and investigated. The rats were injected intravenously with 3.5-4.5 MBq 125I-labeled BR96-biotin. Twenty of the rats underwent WBIA starting 5 or 12 hr after injection. About six blood volumes were passed through an avidin-gel adsorption column during 2 hr. RESULTS: By using WBIA, whole-body radioactivity was reduced by 50%, and plasma activity by 85%. Both directly after completion of WBIA and 33 hr later, the activity uptake in tumors manifested only a nonsignificant decrease as compared with corresponding controls (p > 0.05) and had approximately similar time-activity curves. Uptake ratios for tumor (T):bone marrow, T:liver, T:kidney and T:lung were enhanced 2.3- to 3.5-fold in all three tumor models, as compared with controls. The ratio of liver tumor to bone marrow was improved from 10:1 to 30:1. CONCLUSION: This new method of WBIA yields significantly improved radioimmunotargeting of highly tumor-reactive, internalizing MAb BR96.

Animals↗

PubMed1997

Extracorporeal immunoadsorption compared to avidin chase: enhancement of tumor-to-normal tissue ratio for biotinylated rhenium-188-chimeric BR96.

UNLABELLED: Based on the biodistribution and kinetics of biotinylated 188Re-chimeric BR96 (chiBR96), the enhancement of the tumor-to-normal tissue (T/N) radioactivity ratio using extracorporeal immunoadsorption (ECIA) was evaluated and compared with that of avidin "chase" in colon carcinoma-isografted Brown Norwegian rats. METHODS: Extracorporeal immunoadsorption (ECIA) was performed 6 or 12 hr after intravenous administration of biotinylated 188Re-chiBR96. Radioactivity redistribution was investigated just after ECIA [8 or 14 hr postinjection of the antibody] and 40 or 34 hr after ECIA performance (48 hr postinjection). Avidin was administered intraperitoneally at 6 hr postinjection. Tumor radioactivity uptake and T/N activity ratios of biotinylated 188Re-chiBR96 were compared using ECIA and avidin chase and were also compared with controls. RESULTS: Both ECIA and avidin chase can rapidly increase the radioactivity tumor-to-blood ratio without significantly interfering with the tumor uptake. ECIA at 8 hr postinjection increased the T/N ratios in blood-rich tissues, such as liver and bone marrow, from 6 and 8 to 10 and 18, respectively. Corresponding T/N ratios at 14 hr increased from 9 and 10 to 24 and 36. In contrast, when avidin chase was used, there were no T/N improvements, except in blood. Moreover, avidin chase caused a significant accumulation of radioactivity in the liver. CONCLUSION: The ECIA approach, with direct removal of unbound circulating biotinylated 188Re-chiBR96, thus can rapidly improve and maintain T/N ratios without overloading the liver with radioactivity, in contrast to avidin chase.

Animals↗

PubMed1996

Skin plasma exudation and vasodilatation monitored by external detection of conversion electrons.

We have examined the plasma exudation response of inflammation in guinea pig skin by a noninvasive method and have evaluated the influence of vasodilatation. Indium radionuclides have been used to label plasma and blood and conversion electrons have been detected by an external detector. Transferrin (79,600 Da) was labeled by 111In or 113mIn in vivo and red blood cells were labeled by 111In in vitro. These tracers were given to separate groups of anesthetized guinea pigs and baseline activities were recorded from shaved skin surface areas. Skin prick tests with histamine and saline were performed and time-activity curves were recorded. The measurements with 111In-transferrin and 111In-labeled red blood cells demonstrated that histamine produced dose-dependent accumulation of plasma (up to a 6.5-fold increase) and blood (up to a 2.0-fold increase) in the skin. Hence, about one-third of accumulation of plasma induced by histamine may be explained by vasodilatation. With 113mIn-transferrin as plasma tracer greater effects of histamine were recorded, probably reflecting that the measurements also included deeper sections of the skin. We conclude that the intensity of accumulation of plasma in skin inflammation can be monitored by external detection of conversion electrons from 111In- and 113mIn-transferrin, and that the influence of vasodilatation can be estimated by detection of 111In-labeled red blood cells.

Animals↗

PubMed1996

Indium-111 bleomycin complex for radiochemotherapy of head and neck cancer--dosimetric and biokinetic aspects.

Bleomycin (BLM) is used for the treatment of head and neck cancer. In order to improve the effectiveness of this chemotherapeutic drug, BLM was combined with indium-111. A complex of these agents (111In-BLMC), formed at low pH, was injected intravenously into ten head and neck cancer patients in escalating activities of 75, 175 and 375 MBq. The internally delivered dose to the tumours varied from 0.20 to 2.73 mGy at 75 MBq, from 0.33 to 2.51 mGy at 175 MBq, and from 0.87 to 31.3 mGy at the 375 MBq activity level. Uptake of radioactivity was 0.45+/-0.24x10(-3)% ID/g in primary tumours and 0. 52+/-0.20x10(-3)% ID/g in metastases (at 48 h). Tumour volumes varied from 0.51 to 49.0 cm3. The radioactivity half-lives in the tumours were 30+/-7 h. The activity distribution and penetration into tumour tissue were not affected by increasing the injected activity. There was a positive correlation between BLMC uptake and Ki-67/Mib activity as well as number of mitoses in tumour tissue. These data indicate that 111In-BLMC has potential as a radiochemotherapeutic agent in head and neck cancer and that adjuvant Auger-electron therapy is possible using 114mIn-labelled BLMC.

Adult↗

PubMed1996

Plasma exudation in the skin measured by external detection of conversion electrons.

A novel technique for measurement of plasma exudation in the skin is described. Transferrin labelled in vivo with indium-113m is used as a plasma tracer. The conversion electrons from 113mIn are detected with a polystyrene crystal mounted on a photomultiplier tube. Owing to the short range of the electrons in tissue, background radiation from tracer circulating in underlying tissue will be very small, allowing plasma exudation in the skin to be detected with a high signal to noise ratio. The characteristics of the detector system are described in model experiments using sheets of mylar to simulate soft tissue. The acute inflammatory response to histamine provocation was studied in guinea pig skin. A dose-related increase in count rate representing vasodilatation and plasma exudation was detected over the skin after histamine provocation. The electron radiation system appears suitable for detection of low levels of superficial radioactivity and for pathophysiological studies of the skin.

Animals↗

PubMed1996

Optimization of radioiodination and biotinylation of monoclonal antibody chimeric BR96: an indirect labeling using N-succinimidyl-3-(tri-n-butylstannyl)benzoate conjugate.

Chimeric BR96 (chiBR96) is an oxidant sensitive, highly tumor-reactive and internalizing monoclonal antibody. Radioiodination of chiBR96 with direct labeling methods has a high risk of damaging the antibody's immunoreactivity. Combination of iodination and biotinylation of chiBR96 has been particularly difficult. In present studies, indirect radioiodine labeling by use of a conjugate of N-succinimidyl 3-(tri-n-butylstannyl)benzoate (ATE) was introduced for chiBR96 radioiodination and for combination of iodination and biotinylation of chiBR96. ATE was synthesised, radioiodinated with a modified and simplified method by omitting one step of separation. A same or slightly higher labeling efficiency was obtained comparing to earlier reports. Simultaneous biotinylation of the chiBR96 was performed by use of biotin reagent of N-hydroxysuccinimido-biotin. In a comparative study of biotinylated and unbiotinylated 125I-chiBR96 iodinated with ATE conjugate, it was found that 125I-chiBR96 with or without biotinylation had the same stability, immunoreactivity and biodistribution with a high tumor targeting capacity. Hence, the ATE conjugate radioiodination method enables the combination of iodination and simultaneous biotinylation of chiBR96.

Animals↗

PubMed1996

In vivo absorbed dose measurements with mini-TLDs--parameters affecting the reliability.

Mini-TLDs have been proposed and widely used for in vivo measurements of absorbed doses in radionuclide therapies. The present investigation reports in detail on the signal dependence on different parameters and the accuracy of this method. Rodshaped Teflon-imbedded CaSO4:Dy or LiF thermoluminescent dosimeters (TLDs) with dimensions 0.2 x 0.4 x 5 mm3 were prepared from TLD-discs. To remove paraffin from the mini-TLDs after cutting in a microtome the TLDs were Xylene-treated, which does not affect the sensitivity. Irradiated mini-TLDs are sensitive to illumination. Fading effects in darkness were examined after 60Co-irradiation at temperatures 4, 22 and 37 degrees C. For CaSO4:Dy mini-TLDs fading in air is small. The observed signal loss after implanting CaSO4:Dy mini-TLDs in gel and muscle tissue is the same at constant temperature and is increasing with the temperature. For LiF mini-TLDs the effect of signal loss in gel was smaller than for CaSO4:Dy dosimeters. For 60Co external irradiation supralinearity already starts between 0.5 and 1 Gy for both kinds of dosimeter material. There is a strong pH dependence of the signals from the mini-TLDs. For CaSO4:Dy dosimeters the loss of sensitivity in gel is smaller at higher pHs. For LiF dosimeters the loss of sensitivity is smallest for neutral pH. We conclude that using mini-TLDs for in vivo dosimetry requires careful handling and proper calibration for accuracy in the measurements. Without such calibration errors exceeding 65% for CaSO4:Dy and 40% for LiF may easily occur.

Air↗

PubMed1996

Extracorporeal immunoadsorption from whole blood based on the avidin-biotin concept. Evaluation of a new method.

This study of 36 rats with rat colon adenocarcinoma transplants was carried out to investigate the efficacy of a new method of whole blood immunoadsorption (WBIA) in removing biotinylated monoclonal antibodies (MAbs) directly from unseparated blood, in order to increase 'the tumor/normal-tissue uptake ratio', as compared with extracorporeal immunoadsorption (ECIA) of antibodies from plasma. Compared with the ECIA system, the overall volume of the WBIA system (comprising only a pump, an adsorption column, a drop-chamber and tubings) was less (3.6 vs. 6.2 ml), and procedure duration 2 h less. The 17 rats undergoing the WBIA procedure, started 12 h after i.v. injection of 4.0-4.5 MBq 125I-BR96-biotin, manifested neither hemolysis nor any other complication; no signs of organ edema were found at dissection; whole body and blood radioactivity values were reduced by 51% and 89.5%, respectively. The WBIA method was as effective as ECIA, but technically simpler, safer and more reliable.

Adenocarcinoma↗

PubMed1996

Parameters influencing volume and activity quantitation in SPECT.

Several factors influence the accuracy to which information on the in vivo activity concentration can be obtained from SPECT images. The accuracy in image contrast and the quantitation of volume and activity has here been examined for a SPECT system aimed for absorbed dose determinations in systemic radiation therapy. The influence of source dimensions, object contrast, noise level, energy window width and the reconstruction filter was examined. All the investigated parameters affected the recoveries. Volumes of above 20 cm3 could be quantified to within +/- 20%, for object contrasts of above 96%, and within +/- 40% for object contrasts above 81%, providing limited levels of noise. Both the image contrast and the volume quantification is expected to be improved in situations with low object contrasts, if accurate correction for scattered photons can be developed. Obtained limitations in the quantitation of activity with the present method should be reduced by development of a more accurate background subtraction technique.

Absorption↗

PubMed1996

A Monte-Carlo program converting activity distributions to absorbed dose distributions in a radionuclide treatment planning system.

In systemic radiation therapy, the absorbed dose distribution must be calculated from the individual activity distribution. A computer code has been developed for the conversion of an arbitrary activity distribution to a 3-D absorbed dose distribution. The activity distribution can be described either analytically or as a voxel based distribution, which comes from a SPECT acquisition. Decay points are sampled according to the activity map, and particles (photons and electrons) from the decay are followed through the tissue until they either escape the patient or drop below a cut off energy. To verify the calculated results, the mathematically defined MIRD phantom and unity density spheres have been included in the code. Also other published dosimetry data were used for verification. Absorbed fractions and S-values were calculated. A comparison with simulated data from the code with MIRD data shows good agreement. The S values are within 10-20% of published MIRD S values for most organs. Absorbed fractions for photons and electrons in spheres (masses between 1 g and 200 kg) are within 10-15% of those published. Radial absorbed dose distributions in a necrotic tumor show good agreement with published data. The application of the code in a radionuclide therapy dose planning system, based on quantitative SPECT, is discussed.

Absorption↗

PubMed1996

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.

Animals↗

PubMed1995

Enhanced radioimmunotargeting of 125I-labeled L6-biotin monoclonal antibody (MAb) by combining preload of cold L6 MAb and subsequent immunoadsorption in rats.

The present study investigates whether tumor:normal tissue uptake ratios of radiolabeled monoclonal antibodies can be further improved by a combination of extracorporeal immunoadsorption (ECIA) and preload with unlabeled idiotypic monoclonal antibody. Athymic rats, heterotransplanted with human lung carcinoma under the kidney capsule (SR tumor) and i.m. (IM tumor), were divided into four study groups: controls, ECIA, preload, and combined preload+ECIA. The preload+ECIA procedure reduced the whole-body and plasma activity by 48 and 89%, respectively. After such combined procedure, the uptake of 125I-labeled L6-biotin in SR tumors was unchanged, while the uptake in normal tissues was considerably reduced. Tumor (T):bone marrow ratio was then increased by 17.5 times (after ECIA) and by 4.5 times (24 h after ECIA). Similar enhancements were achieved for T:liver and T:kidney ratios. For the IM tumors, the ratios were not as high as for SR tumors. The effects on T:normal ratios of preload+ECIA in combination were synergistic. The combined procedure resulted both in an increased uptake and prolonged persistence of 125I-labeled L6-biotin in the SR tumors and also in a reduction of corresponding uptake values in organs critical for radiation.

Animals↗

PubMed1995

Necrosis of malignant gliomas after intratumoral injection of 201Tl in vivo in the rat.

Fourteen adult Fischer 344 rats were inoculated in vivo unilaterally in the caudate nucleus in the brain with malignant RG 2 glioma cells. By 3 weeks a tumor with a diameter of 3-6 mm normally develops. Ten animals which survived the repeated periods of anesthesia and thallium (Tl) injections (intratumorally three times of 201Tl, 15-23 days after inoculation) showed a prolonged retention of radioactivity at the site of injection with no uptake in other organs except for the kidneys. Singular circumscribed necroses were found post-mortem at the site of injection, comprising malignant glioma tumor tissue, which in six animals was absent, in three animals was markedly reduced in size compared with controls and in one animal had the expected size. In four animals metastases were found in distant locations in the brain; in three of these cases there was a retention of radioactivity in the tumor. The selective necrotizing effect on the tumor cells is interpreted as mainly due to emission of Auger electrons from intracellularly accumulated 201Tl, giving rise to very high energy deposition in the vicinity of the cell nucleus. The results should also have implications for the treatment of human malignant gliomas.

Animals↗

PubMed1994

A general extracorporeal immunoadsorption method to increase tumor-to-tissue ratio.

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.

Animals↗

PubMed1994

Small animal imaging with pinhole single-photon emission computed tomography.

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.

Algorithms↗

PubMed1994

Parameters to consider for measurements of absorbed doses in vivo with mini-thermoluminescent dosimeters.

BACKGROUND: For systemic radiation therapy, i.e., radioimmunotherapy, there is a demand for direct methods of measuring the absorbed dose in vivo. One such method is the use of mini-thermoluminescent dosimeters (TLDs). This paper reports an investigation of the sensitivity of tissue implanted mini-TLDs (calcium sulfate:Dy, 0.2 x 0.4 x 5.0 mm). METHODS: After being irradiated with cobalt-60, the mini-TLDs were left for as long as 9 days in air, gel, and muscle tissue. RESULTS: There was an extensive signal loss, which increased with time, except in air. After 9 days in gel or muscle tissue at room temperature, the signal was decreased to one third of its original value. The dosimeters needed to be kept in constant darkness. There was a strong pH dependence, with a loss of sensitivity of 63% at a pH below 5, which got smaller at higher pH values and reached 10% at pH = 10. CONCLUSIONS: When using mini-TLDs in vivo, one must calibrate the dosimeters in similar milieus, unless the position of the dosimeters in tissue after implantation can be monitored for temperature, pH, and liquid flow.

Animals↗

PubMed1994

Radio-immunotherapy dosimetry with special emphasis on SPECT quantification and extracorporeal immuno-adsorption.

Results from therapeutic trials with radiolabelled monoclonal antibodies are difficult to compare, because of lack of accurate macroscopic and microscopic dosimetry for both tumours and normal tissues. Requirements for such a dosimetry are covered in the paper. Accurate in vivo dosimetric measurement techniques for verification of calculated absorbed doses are also needed to verify treatment planning. In the review, important topics related to dosimetry in therapeutic trials in RIT are covered, such as, absorbed-dose calculations and activity-quantification techniques for planar imaging and SPECT. The latter is particularly discussed, including a summary of different correction techniques. Absorbed-dose calculations and treatment-planning techniques are also discussed. Possible ways of enhancing the therapeutic ratio are reviewed, especially the novel technique with extracorporeal immuno-adsorption. The review could form the basis of the development of future treatment-planning protocols and for dosimetry calculations in radio-immunotherapy, considering some of the most important parameters for approaching an accurate in vivo dosimetry.

Antibodies, Monoclonal↗

PubMed1994

Correlation of beta-camera imaging and immunohistochemistry in radioimmunotherapy using 90Y-labeled monoclonal antibodies in ovarian cancer animal models.

Tumor stroma contains much fibrin and monoclonal antifibrin antibody targeting is possible in tumors. In this study, nude mouse human ovarian carcinoma xenograft specimens were investigated after treatment with 90Y-labeled monoclonal antifibrin antibody Fab fragment or with 90Y-labeled OC125-monoclonal antibody F(ab')2 fragments. The mice received the radioimmunotherapy activity either intratumorally, intraperitoneally, or intravenously. Beta-camera imaging (BCI) is a novel device for studying activity distribution in tissue specimens and, together with immunohistochemistry (IHC) with OC125, antifibrin, anticarcinoembryonic antigen, anti-cytokeratin, and anti-placental alkaline phosphatase antibodies, was used for correlation of activity distribution of tissue specimens. These results were in concordance: Antigen distribution measured with IHC and radioactivity distribution were similar with the same antibodies, antifibrin, and OC125: However, these antigens demonstrated rather different distribution. Tissue studies revealed that activity was concentrated also in the necrotic tumor tissue, indicating that cell death was also caused by radiation. Differences in the tumor cell morphology were observed using different routes of administration. With BCI, it is possible to quantitate activities in frozen sections (microdosimetry), and these results were in concordance with absolute activities as measured by tissue sampling and well-counting. Three-dimensional reconstruction of tissue slices combined with radioactivity distribution measured with BCI allows estimation of total absorbed radiation dose in tumor after an appropriate dose planning.

Animals↗