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S E Strand

Publications and source records attributed to S E Strand.

At least 19 recordsLinked to original sources

Reduced postnatal cerebral glucose metabolism measured by PET after asphyxia in near term fetal lambs.

The effects of fetal asphyxia on cerebral function and development, involve the transition from fetal to neonatal life. Changes in cerebral glucose metabolism may be an early postnatal indicator of fetal asphyxia. The objective is to develop an experimental lamb model involving the transition from fetal to neonatal life and to examine the effect of fetal asphyxia with cerebral hypoxic ischemia on early postnatal cerebral glucose metabolism. Fetal asphyxia was induced by total umbilical cord occlusion in eight near-term fetal lambs (134-138 days) with the ewe under isoflurane-opiate anesthesia. The mean occlusion time until cardiac arrest was 14.5 (4.2) min (SD). Lambs were immediately delivered and standardized resuscitation was instituted after 2 min asystole. At 4 hr postnatal age, [18-F]Fluoro-2-deoxy-glucose (18-FDG) was injected intravenously in eight asphyxiated lambs and in eight controls. Cerebral glucose metabolism was examined by positron emission tomography (PET). As a result the mean arterial blood pressure, acid-base values, blood glucose and serum lactate at 4 hr postnatal age did not differ significantly between lambs subjected to umbilical cord occlusion and controls. EEG was abnormal in all lambs subjected to cord occlusion and normal in the controls at 4 hr postnatal age. Global cerebral metabolic rate (CMRgl) as determined by PET was significantly lower in lambs subjected to cord occlusion mean/median (SD) 22.2/19.6 (8.4) micromol/min/100 g) than in controls mean/median (SD) 37.8/35.9 (6.1); P < 0.01). Global CMRgl is significantly reduced in newborn lambs 4 hr after fetal asphyxia induced by umbilical cord occlusion. A reduction in CMRgl is an early indicator of global hypoxic cerebral ischemia.

Acidosis↗

Anaerobic biodegradation of naphthalene, phenanthrene, and biphenyl by a denitrifying enrichment culture.

In previous results [Rockne and Strand (1998) Environ. Sci. Technol. 32, 2962-3967], anaerobic biodegradation of the polycyclic aromatic hydrocarbons, naphthalene, phenanthrene, and biphenyl in a fluidized bed reactor (FBR) enrichment was demonstrated. In this paper, re-feeding and mineralization experiments with sub-cultures of the nitrate-reducing enrichment are described. The subcultures continued to remove the PAHs after three feedings. PAH biodegradation ceased when nitrate was depleted and resumed when the enrichment was fed nitrate, demonstrating that PAH biodegradation was dependent upon nitrate reduction. Tests with radiolabeled PAH confirmed that PAH was mineralized, although the extent of mineralization differed greatly with different PAHs. Only partial mineralization (17% of initial carbon) was observed when the culture was fed naphthalene, whereas nearly complete mineralization (96%) was observed with phenanthrene. PAH carbon was incorporated into cell mass and mineralized after complete biodegradation of the PAHs, with 78-102% recoveries of radiolabel for naphthalene and phenanthrene, respectively. PAH carbon incorporation into biomass also varied considerably. Minor assimilation of biphenyl or phenanthrene was observed in the culture, whereas extensive assimilation of naphthalene carbon (57%) was observed when the culture was challenged with naphthalene. PAH degradation was approximately stoichiometric with the amount of nitrate consumed. Headspace analysis showed production of N2O, suggesting the enrichment coupled the biodegradation of PAH to denitrification.

Anaerobiosis↗

Distribution of iodine 125-labeled alpha1-microglobulin in rats after intravenous injection.

The 28-kd plasma protein alpha(1)-microglobulin is found in the blood of mammals and fish in a free, monomeric form and as high-molecular-weight complexes with molecular masses above 200 kd. In this study, iodine 125-labeled free and high-molecular weight rat alpha(1)-microglobulin (a mixture of alpha(1)-microglobulin/alpha(1)-inhibitor-3 and alpha(1)-microglobulin/fibronectin complexes) were injected intravenously into rats. The distribution of the proteins was measured by using scintillation camera imaging. Both forms of (125)I-labeled alpha(1)-microglobulin were rapidly cleared from the blood, with a half-life of 2 and 16 minutes for the initial and late phase, respectively, for free alpha(1)-microglobulin; and a half-life of 3 and 130 minutes for the initial and late phase, respectively, for the complexes. After 45 minutes, 6%, 16%, 27%, 13%, and 34% of the free (125)I-labeled alpha(1)-microglobulin and 18%, 21%, 6%, 10%, and 42% of the (125)I-labeled alpha(1)-microglobulin complexes were found in the blood, gastrointestinal tract, kidneys, liver, and the remainder of the body, respectively. The local distribution of injected (125)I-labeled alpha(1)-microglobulin in intestines and kidneys was investigated by microscopy and autoradiography. In the intestine, both forms were distributed in the basal layers, villi, and luminal contents. The results also suggested intracellular labeling of epithelial cells. Well-defined local regions containing higher concentrations of injected protein could be seen in the intestine. In the kidneys, both forms were found mostly in the cortex. Free (125)I-labeled alpha(1)-microglobulin was found predominantly in epithelial cells of a subset of the tubules, whereas the (125)I-labeled complexes were more evenly distributed. Intracellular labeling was indicated for both alpha(1)-microglobulin forms. The results thus indicate a rapid transport of (125)I-labeled alpha(1)-microglobulin from the blood to most tissues.

Animals↗

Cerebral glucose metabolism measured by positron emission tomography in term newborn infants with hypoxic ischemic encephalopathy.

Total and regional cerebral glucose metabolism (CMRgl) was measured by positron emission tomography with 2-((18)F) fluoro-2-deoxy-D-glucose ((18)FDG) in 20 term infants with hypoxic ischemic encephalopathy (HIE) after perinatal asphyxia. All infants had signs of perinatal distress, and 15 were severely acidotic at birth. Six infants developed mild HIE, twelve moderate HIE, and two severe HIE during their first days of life. The positron emission tomographic scans were performed at 4-24 d of age (median, 11 d). One hour before scanning, 2-3.7 MBq/kg (54-100 microCi/kg) (18)FDG was injected i.v. No sedation was used. Quantification of CMRgl was based on a new method employing the glucose metabolism of the erythrocytes, requiring only one blood sample. In all infants, the most metabolically active brain areas were the deep subcortical parts, thalamus, basal ganglia, and sensorimotor cortex. Frontal, temporal, and parietal cortex were less metabolically active in all infants. Total CMRgl was inversely correlated with the severity of HIE (p < 0.01). Six infants with mild HIE had a mean (range) CMRgl of 55.5 (37.7-100.8) micromol.min(-1).100 g(-1), 11 with moderate HIE had 26.6 (13.0-65.1) micromol.min(-1).100 g(-1), and two with severe HIE had 10.4 and 15.0 micromol.min(-1).100 g(-1), respectively. Five of six infants who developed cerebral palsy had a mean (range) CMRgl of 18.1 (10.2-31.4) micromol.min(-1).100 g(-1) compared with 41.5 (13.0-100.8) micromol.min(-1).100 g(-1) in the infants with no neurologic sequela at 2 y. We conclude that CMRgl measured during the subacute period after perinatal asphyxia in term infants is highly correlated with the severity of HIE and short-term outcome.

Brain↗

Registration of emission and transmission whole-body scintillation-camera images.

UNLABELLED: In this work, a method for registration of whole-body (WB) scintillation-camera images is presented. The primary motive for the development is to perform activity quantification using the conjugate view method on an image basis. Accurate image registration is required for sequential anterior and posterior scans, for serial emission images for analysis of the biokinetics, and for transmission and emission images for a pixel-based attenuation correction. METHODS: Registration is performed by maximization of the mutual information. The spatial transformation has been tailored for the registration of WB images and is composed of global and local transformations, including rigid, projective, and curved transformations. A coarse registration is first performed using cross-correlation and direct pixel scaling. Optimization is then performed in a sequence, beginning with the 2 legs independently, followed by the upper body and head. Evaluation is performed for clinical images of an (131)I-labeled monoclonal antibody and for Monte Carlo-simulated images. An anthropomorphic WB computer phantom, which has been especially modified to match the patient position during WB scanning, is used for the simulations. RESULTS: For simulated images, registration errors are within 1 pixel (<3.6 mm) for a sufficient image count level. Separate evaluation of the influence of noise shows that the errors increase below a total image count of approximately 10(5) (signal-to-noise ratio, approximately 4). For clinical evaluations, the deviations between point markers are 9 +/- 5 mm. CONCLUSION: An automatic registration method for WB images has been developed, which is applicable to emission-emission and transmission-emission registration. This method has been applied in more than 50 clinical studies and has shown to be robust and reliable.

Gamma Cameras↗

Enhanced metabolism of halogenated hydrocarbons in transgenic plants containing mammalian cytochrome P450 2E1.

Chlorinated solvents, especially trichloroethylene (TCE), are the most widespread groundwater contaminants in the United States. Existing methods of pumping and treating are expensive and laborious. Phytoremediation, the use of plants for remediation of soil and groundwater pollution, is less expensive and has low maintenance; however, it requires large land areas and there are a limited number of suitable plants that are known to combine adaptation to a particular environment with efficient metabolism of the contaminant. In this work, we have engineered plants with a profound increase in metabolism of the most common contaminant, TCE, by introducing the mammalian cytochrome P450 2E1. This enzyme oxidizes a wide range of important pollutants, including TCE, ethylene dibromide, carbon tetrachloride, chloroform, and vinyl chloride. The transgenic plants had a dramatic enhancement in metabolism of TCE of up to 640-fold as compared with null vector control plants. The transgenic plants also showed an increased uptake and debromination of ethylene dibromide. Therefore, transgenic plants with this enzyme could be used for more efficient remediation of many sites contaminated with halogenated hydrocarbons.

Animals↗

Palliative radiation with a radiolabeled diphosphonate (rhenium-186 etidronate) in patients with hormone-refractory disseminated prostate carcinoma.

MATERIAL AND METHODS: The present study investigates the safety and efficacy of 2590 MBq rhenium-186 (186Re) etidronate (i.e. twice the activity normally used) administered intravenously in 15 patients with disseminated prostatic carcinoma and bone pain. RESULTS: Pain relief was observed in 11 of 14 evaluable patients (79%), 4 of whom became completely free from pain. Five of the responding patients also noted an improvement in daily activity and two found it possible to reduce or discontinue morphine medication. Pain relief occurred within one week in four patients, and within two weeks in eight of the responding patients. The mean duration of pain relief after the first course of 186Re-etidronate was 6 weeks (range 4-10). The toxicity was mild (< or = grade 2), transient, and restricted to hematological toxicity. CONCLUSIONS: 186Re-etidronate provided rapid pain-relief and had mild toxicity in most patients with disseminated hormone-refractory prostatic carcinoma, but doubling the activity did not markedly improve the efficacy.

Bone Neoplasms↗

Anaerobic naphthalene degradation by microbial pure cultures under nitrate-reducing conditions.

Pure bacterial cultures were isolated from a highly enriched denitrifying consortium previously shown to anaerobically biodegrade naphthalene. The isolates were screened for the ability to grow anaerobically in liquid culture with naphthalene as the sole source of carbon and energy in the presence of nitrate. Three naphthalene-degrading pure cultures were obtained, designated NAP-3-1, NAP-3-2, and NAP-4. Isolate NAP-3-1 tested positive for denitrification using a standard denitrification assay. Neither isolate NAP-3-2 nor isolate NAP-4 produced gas in the assay, but both consumed nitrate and NAP-4 produced significant amounts of nitrite. Isolates NAP-4 and NAP-3-1 transformed 70 to 90% of added naphthalene, and the transformation was nitrate dependent. No significant removal of naphthalene occurred under nitrate-limited conditions or in cell-free controls. Both cultures exhibited partial mineralization of naphthalene, representing 7 to 20% of the initial added (14)C-labeled naphthalene. After 57 days of incubation, the largest fraction of the radiolabel in both cultures was recovered in the cell mass (30 to 50%), with minor amounts recovered as unknown soluble metabolites. Nitrate consumption, along with the results from the (14)C radiolabel study, are consistent with the oxidation of naphthalene coupled to denitrification for NAP-3-1 and nitrate reduction to nitrite for NAP-4. Phylogenetic analyses based on 16S ribosomal DNA sequences of NAP-3-1 showed that it was closely related to Pseudomonas stutzeri and that NAP-4 was closely related to Vibrio pelagius. This is the first report we know of that demonstrates nitrate-dependent anaerobic degradation and mineralization of naphthalene by pure cultures.

Bacteria, Anaerobic↗

Radiation dosimetry in nuclear medicine.

Radionuclides are used in nuclear medicine in a variety of diagnostic and therapeutic procedures. A knowledge of the radiation dose received by different organs in the body is essential to an evaluation of the risks and benefits of any procedure. In this paper, current methods for internal dosimetry are reviewed, as they are applied in nuclear medicine. Particularly, the Medical Internal Radiation Dose (MIRD) system for dosimetry is explained, and many of its published resources discussed. Available models representing individuals of different age and gender, including those representing the pregnant woman are described; current trends in establishing models for individual patients are also evaluated. The proper design of kinetic studies for establishing radiation doses for radiopharmaceuticals is discussed. An overview of how to use information obtained in a dosimetry study, including that of the effective dose equivalent (ICRP 30) and effective dose (ICRP 60), is given. Current trends and issues in internal dosimetry, including the calculation of patient-specific doses and in the use of small scale and microdosimetry techniques, are also reviewed.

Alpha Particles↗

Anaerobic transformation of 1,1,1-trichloroethane by municipal digester sludge.

Anaerobic transformations of 1,1,1-trichloroethane (TCA), 1,1-dichloroethane (DCA), and chloroethane (CA) were studied with sludge from a lab-scale, municipal wastewater sludge digester. TCA was biologically transformed to DCA and CA and further to ethane by reductive dechlorination. TCA was also converted to acetic acid and 1,1-dichloroethene (11DCE) by cell-free extract. 11DCE was further biologically converted to ethene. This pathway was confirmed by transformation tests of TCA, DCA and CA, by tests with cell-free extract, and by chloride release during TCA degradation. With cell-free extract, acetic acid accounted for approximately 90% of the TCA transformed; tests with live cells indicate that the fraction of TCA transformed by this pathway decreased with lower biomass. The dechlorination of DCA to CA and CA to ethane was not stoichiometric. A high rate of TCA removal was observed under the experimental conditions. The results indicate that removal of TCA in anaerobic digestion should be complete, but DCA and CA could persist in a normally operating digester.

Anaerobiosis↗

Survival of mammalian cells exposed to ultrahigh dose rates from a laser-produced plasma x-ray source.

PURPOSE: To determine whether intense laser-produced x rays have an increased radiation hazard. MATERIALS AND METHODS: Mammalian cells were exposed to x rays from a laser-produced plasma that produced ultrahigh peak absorbed dose rates, up to a factor of 10(10) higher than those produced by conventional x rays used in imaging. The cell survival was studied as a function of the absorbed dose. The survival of mammalian cells exposed to high peak absorbed dose rates with laser-produced x rays was compared with the survival of cells exposed to standard absorbed dose rates with conventional x-ray sources. Comparative survival studies were performed by using a conventional x-ray tube and a cobalt 60 source. The absorbed doses in the irradiation field were measured with thermoluminescent dosimeters. RESULTS: Cell survival following irradiation by filtered, laser-produced x rays with a high dose rate was not markedly different from the survival following irradiation by conventional sources. There was, however, a notable difference between the survival after exposure to filtered, laser-produced x rays and the survival after exposure to unfiltered laser-produced x rays. CONCLUSION: Exposure to filtered, laser-produced x rays with a high dose rate does not lead to increased harm to mammalian cells exposed in vitro compared with the harm from exposure to x rays from conventional sources, which indicates that the use of high-power laser facilities for medical imaging is justified.

Animals↗

A new rectal model for dosimetry applications.

UNLABELLED: A revised geometric representative model of the lower part of the colon, including the rectum, the urinary bladder and prostate, is proposed for use in the calculation of absorbed dose from injected radiopharmaceuticals. The lower segment of the sigmoid colon as described in the 1987 Oak Ridge National Laboratory mathematical phantoms does not accurately represent the combined urinary bladder/rectal/prostate geometry. In the revised model in this study, the lower part of the abdomen includes an explicitly defined rectum. The shape of sigmoid colon is more anatomically structured, and the diameters of the descending colon are modified to better approximate their true anatomic dimensions. To avoid organ overlap and for more accurate representation of the urinary bladder and the prostate gland (in the male), these organs are shifted from their originally defined positions. The insertion of the rectum and the shifting of the urinary bladder will not overlap with or displace the female phantom's ovaries or the uterus. In the adult male phantom, the prostatic urethra and seminal duct are also included explicitly in the model. The relevant structures are defined for the newborn and 1-, 5-, 10- and 15-y-old (adult female) and adult male phantoms. METHODS: Values of the specific absorbed fractions and radionuclide S values were calculated with the SIMDOS dosimetry package. Results for 99mTc and other radionuclides are compared with previously reported values. RESULTS: The new model was used to calculate S values that may be crucial to calculations of the effective dose equivalent. For 131I, the S (prostate<--urinary bladder contents) and S (lower large intestine [LLI] wall<--urinary bladder contents) are 6.7 x 10(-6) and 3.41 x 10(-6) mGy/MBq x s, respectively. Corresponding values given by the MIRDOSE3 computer program are 6.23 x 10(-6) and 1.53 x 10(-6) mGy/MBq x s, respectively. The value of S (rectum wall<--urinary bladder contents) is 4.84 x 10(-5) mGy/MBq x s. For 99mTc, we report S (testes<--prostate) and S (LLI wall<--prostate) of 9.41 x 10(-7) and 1.53 x 10(-7) mGy/MBq x s versus 1.33 x 10(-6) and 7.57 x 10(-6) mGy/MBq x s given by MIRDOSE3, respectively. The value of S (rectum wall<--prostate) for 99mTc is given as 4.05 x 10(-6) mGy/MBq x s in the present model. CONCLUSION: The new revised rectal model describes an anatomically realistic lower abdomen region, thus giving improved estimates of absorbed dose. Due to shifting the prostate gland, a 30%-45% reduction in the testes dose and the insertion of the rectum leads to 48%-55% increase in the LLI wall dose when the prostate is the source organ.

Adult↗

Comparison of 125I- and (111)In-labeled monoclonal antibody BR96 for tumor targeting in combination with extracorporeal immunoadsorption.

Extracorporeal whole blood immunoadsorption (ECIA) accelerates the clearance of radiolabeled monoclonal antibodies (mAbs) without significantly affecting tumor uptake by removing the excess of these mAbs from the blood, thus increasing tumor:normal tissue (T:N) ratios. The present study is focused on comparing the capacity of ECIA in tumor targeting with the same mAb (chiBR96-biotin) labeled with either (111)In or 125I. Forty-five Brown Norwegian rats with syngeneic rat colon carcinoma isografted both in liver and intramuscularly were used. chiBR96 is a highly tumor-specific mAb directed against the Lewis-type antigen. ECIA of whole blood was started 15 h after the injection of 125I- or (111)In-labeled BR96-biotin. The procedure lasted for 2 h and was repeated for (111)In-labeled BR96-biotin in a few rats after 3 or 24 h. ECIA reduced the whole body activity by the same magnitude (between 39% and 52%), irrespective of whether (111)In- or 125I-labeled chiBR96 was used. A similar observation was also made for the reduction in blood radioactivity after ECIA (79-94%). Time-activity curves during ECIA showed that the major reduction (approximately 85%) in blood radioactivity occurred during the first 45-60 min. Repeating the ECIA with (111)In-BR96 caused only an additional minimal reduction of blood activity, whereas a further reduction of whole body activity of 14-20% was achieved. The T:N uptake ratios were significantly enhanced immediately after ECIA with (111)In- or 125I-labeled chiBR96. Due to greater accumulation of (111)In-BR96 in tumors, a long-term improvement in T:N ratios was obtained after ECIA compared with 125I-labeled BR96. Our results therefore indicate that (111)In/(90Y)-labeled BR96-biotin could be more advantageous than 125I/131I for radioimmunotargeting/radioimmunotherapy in combination with ECIA due to better activity retention by the tumor.

Animals↗

Radioimmunotherapy using 131I-labeled anti-CD22 monoclonal antibody (LL2) in patients with previously treated B-cell lymphomas.

Experience in using rapidly internalizing antibodies, such as the anti-CD22 antibody, for radioimmunotherapy of B-cell lymphomas is still limited. The present study was conducted to assess the efficacy and toxicity of a 131I-labeled anti-CD22 monoclonal antibody (mAb), LL2, in patients with B-cell lymphomas failing first- or second-line chemotherapy. Eligible patients were required to have measurable disease, less than 25% B cells in unseparated bone marrow, and an uptake of 99mTc-labeled LL2Fab' in at least one lymphoma lesion on immunoscintigram. Eight of nine patients examined with immunoscintigraphy were unequivocally found to have an uptake, and therapy with 131I-labeled anti-CD22 [1330 MBq/m2 (36 mCi/m2)] preceded by 20 mg of naked anti-CD22 mAb was administered. Three patients achieved partial remission (duration, 12, 3, and 2 months), and one patient with progressive lymphoma showed stable disease for 17 months. Four patients exhibited progressive disease. The toxicity was hematological. Patients with subnormal counts of neutrophils or platelets before therapy seemed to be more at risk for hematological side effects. Radioimmunotherapy in patients with B-cell lymphomas using 131I-labeled mouse anti-CD22 can induce objective remission in patients with aggressive as well as indolent lymphomas who have failed prior chemotherapy.

Adult↗

An alternative method to normalize clinical FDG studies.

UNLABELLED: An alternative method of determining the integrated input function, necessary in the quantitative [18F]fluorodeoxyglucose (FDG) autoradiographic model, has been developed. Using erythrocytes as reference tissue, researchers require only one blood sample after injection of FDG to obtain the integrated input function. METHODS: The amount of FDG-6-PO4 in the erythrocytes is proportional to their exposure to FDG, that is, the integrated input function. Free FDG is removed by washing the erythrocytes twice. Inter- and intraindividual differences of the metabolic rate of erythrocytes are corrected for by an in vitro incubation with a known amount of FDG. RESULTS: Validation of the proposed method was done by correlating the integrated input function, based on the glucose metabolism of the erythrocytes, to the integrated input function obtained by multiple venous blood samples. The new method provides the integrated input function with an accuracy better than +/-8%. CONCLUSION: By using erythrocytes as a reference tissue, researchers can determine the integrated input function in the quantitative FDG autoradiographic model with an accuracy sufficient for clinical PET studies. The simplicity of the method also makes it suitable for FDG studies on small children. With two samples, the method can also be used for a simplified graphical Patlak analysis.

Erythrocytes↗

Improving tumor-to-normal-tissue ratios of antibodies by extracorporeal immunoadsorption based on the avidin-biotin concept: development of a new treatment strategy applied to monoclonal antibodies murine L6 and chimeric BR96.

BACKGROUND: Several strategies have been explored to accelerate monoclonal antibody (MAb) conjugate clearance without affecting intratumoral uptake. One of the most promising is extracorporeal immunoadsorption (ECIA), in which excess radiolabeled MAb circulating in blood is removed. METHODS: Extracorporeal immunoadsorption (ECIA) based on the avidin-biotin concept enables direct adsorption of radiolabeled and biotinylated MAb from plasma and consequently increases the tumor-to-normal-tissue uptake ratio by reducing background radioactivity in all radiosensitive organs. Because the concept is based on an antibody's being biotinylated prior to injection, the blood clearance efficiency is independent of the idiotype or isotype of the antibody employed. As a result, there is no need to develop new adsorption columns for each antibody system used. We have technically simplified the method recently by removing biotinylated MAb directly from blood without separation from plasma preceding the removal. The current study focused on both the development of ECIA and evaluating the effects of ECIA in terms of tumor targeting with two biotinylated radiolabeled MAbs that have different biokinetics, namely, murine MAb L6 and chimeric Mab BR96. RESULTS: The start time of ECIA should be determined for each MAb individually before radioimmunotherapy and be based on previous tumor biokinetics. BR96 with rapid tumor targeting seems more suitable than L6 for the ECIA procedure; it allows the procedure to start earlier and thereby further reduce whole body activity and exposure of critical organs to radiation. CONCLUSIONS: ECIA enables direct adsorption of radiolabeled and biotinylated monoclonal antibody from blood and consequently increases the tumor-to-normal-tissue uptake ratio. The method is even applicable to both the internalizing and already highly tumor-selective BR96 in a syngeneic tumor model.

Animals↗

Early prediction of treatment outcome in head and neck cancer with 2-18FDG PET.

The development of alternative treatment regimens in clinical oncology has increased the need for early prediction of cancer therapy outcome. The aim of this study was, early in the treatment phase, to identify patients with advanced head and neck cancer, responding or not responding to initiated therapy. The tumour metabolic rate of glucose (MRgl) examined by 2-18FDG-PET was determined in 17 patients before and after the first weeks of either radiotherapy (16-35 Gy) or one course of combination chemotherapy. Metabolic values uptake values normalized to plasma activity integrals--were correlated to loco-regional outcome, as evaluated 5-6 weeks after completion of treatment. Initial low tumour MRgl (<20 micromol/min/100 g tissue), in primary lesions or regional metastases, predicted a local complete response. When a high initial tumour MRgl was found, the magnitude of the reduction of MRgl in the second PET examination might be an adjunct in predicting local tumour response.

Adult↗

Biokinetics of indium-111-bleomycin complex in head and neck cancer--implementations for radiochemotherapy.

Bleomycin (BLM) has been used successfully for treatment of head and neck cancer. Combining radionuclide therapy with chemotherapy is a fascinating possibility. We have studied the biokinetics of BLM labeled with indium-111 (In-111). A complex formed at low pH had an activity of 100 MBq/mg BLM. This substance was intravenously injected into 10 head and neck cancer patients in escalating doses of 75, 175, and 375 MBq. Scintigraphic data from these patients were compared with tissue samples obtained at surgery. The activity distribution and penetration into tumor tissue was not affected by increasing the injected activity. In-111-BLMC uptake was directly proportional to Ki-67/MIB-1 activity and number of mitoses in tumor tissue. Based on the biokinetics, dosimetric calculations for In-111 and In-114m have been performed. S values for realistic geometry (a phantom designed from Patient CT) have been calculated. In-114m could deliver a 4-fold absorbed radiation dose into the tumor compared with In-111. We think that In-111-BLMC could be used for radiochemotherapy in head and neck cancer or adjuvant Auger-electron therapy using In-114m combined with BLM. Further studies on cellular dosimetry should be undertaken.

Adult↗