Uptake Of Radiolabel Research Articles

Methylation status of DNA cytosine during the course of induction of liver cancer in hamsters by hydrazine sulfate.

Hydrazine, which is toxic and carcinogenic to rodent liver, has been shown to react with endogenous formaldehyde in the liver to form formaldehyde hydrazone (CH2 = N-NH2), an alkylating intermediate that methylates DNA guanine at the N7- and O6-positions. Studies were conducted to investigate the role of chronic hydrazine-induced hepatotoxicity on DNA maintenance methylation (formation of 5-methyldeoxycytosine) and the development of liver cancer. Male Syrian golden hamsters were given hydrazine sulfate (0, 170, 340 and 510 mg/l) in drinking water for 21 months (average dose 0, 4.2, 6.7 and 9.8 mg/kg body wt hydrazine as the free base). Hepatotoxicity was evaluated histologically, and regenerative DNA synthesis and maintenance methylation were measured as the incorporation of [methyl-14C]thymidine into DNA and the methyl moiety of [methyl-3H]methionine into 5-methyldeoxycytosine in DNA, respectively. Methylguanines were detected in liver DNA at the first observation time of 6 months of treatment; levels of these aberrant bases decreased or became undetectable at 14 months, and increased in a dose-related manner for the remainder of the study. DNA adducts persisted in the highest dose group throughout the study, repeating the results of a similar study previously reported by this laboratory (Bosan et al., Carcinogenesis, 8, 439-444, 1987). Linear regression analysis of thymidine and methionine methyl moiety incorporation into liver DNA suggested impairment of maintenance methylation of DNA (5-methyldeoxycytosine) in the middle and high exposure animals. Hepatic adenomas and hepatocellular carcinomas developed in a dose-related manner and were highly correlated to decreased uptake of radiolabel from methionine into DNA 5-methylcytosine. These results are part of a continuing study on alteration of maintenance methylation during hydrazine induction of liver cancer.

A simple flow cytometric technique to quantify rod outer segment phagocytosis in cultured retinal pigment epithelial cells.

The primary aim of this study was to develop and characterize a simple flow cytometric method of quantifying rod outer segment (ROS) phagocytosis in cultured retinal pigment epithelial (RPE) cells. A secondary aim was to compare the kinetics of ROS phagocytosis in an immortal human RPE cell line with untransformed human RPE cells. Flow cytometry was performed on RPE cells that had been challenged with fluorescein isothiocyanate-labeled ROS (FITC-ROS) and phagocytosis was calculated by subtracting background cellular autofluorescence. Non-specific uptake of fluorescent label was negligible and RPE cells phagocytosed FITC-ROS and unlabeled ROS with equal efficacy. The kinetics of FITC-ROS phagocytosis in the D407 RPE cell line differed from early passage untransformed human RPE cultures. FITC-ROS phagocytosis proceeded at a fairly linear rate for the first 12 h in the 3 human cell cultures studied, but was rapid for the first 3 h before slowing in the D407 cells. Within all cell populations, there was a heterogeneity of phagocytic activity which varied with time. This automated technique for measuring phagocytosis is rapid, simple, highly accurate, avoids radiation hazards, and permits study of heterogeneity within cell populations. The biochemistry, physiology and pathophysiology of the interactions between retinal pigment epithelial (RPE) cells and photoreceptors continue to be areas of considerable research interest (1, 2, 3). Vital to such work is the ability to accurately quantify rod outer segment (ROS) phagocytosis by RPE cells. Current in vitro techniques of measuring ROS phagocytosis use either automated or manual methods to count phagosomes. While manual counting techniques offer the advantage of visual quality control, they are highly labor intensive, there is a practical limitation to the number of phagosomes that can be counted, and measurements suffer from relatively large standard errors (3). Automated methods include scintillation counting and flow cytometry. Problems with radiolabels include radiation hazards, nonspecific radiolabel uptake, and limited visual control (3). Flow cytometry, on the other hand, circumvents nearly all of these problems and may prove to be the optimal phagocytosis assay.

Gonadotrophic hormone inEulalia viridis(Polychaeta, Annelida): Stimulation of vitellogenesis

Summary Incorporation of 3H-leucine into TCA extracted, water soluble oocyte proteins is significantly enhanced in in vivo cultures of Eulalia viridis which have intact supra-oesophageal ganglia and those which have undergone replacement therapy when compared to decerebrate treatments. This response is gonad specific, with no differences in the rate of uptake of 3H-leucine into gut proteins between treatments. There was no significant difference in the rate of protein synthesis between oocytes cultured in vitro in the presence or absence of supra-oesophageal ganglion homogenate on culture medium containing 3H-leucine. However, oocytes cultured in the presence of supra-oesophageal ganglion homogenate do show a significant increase in the rate of uptake of radiolabel when compared to oocytes cultured in the absence of prostomial homogenate when cultured on medium containing 3H-labelled oocyte protein. These results indicate the presence of a gonadotrophic hormone in the supra-oesophageal ganglion of Eulalia...

Hutchinson-Gilford Progeria Fibroblasts Exhibit Metabolically Normal Uridine Uptake and RNA Synthetic Rates

The accelerated aging disease Hutchinson-Gilford progeria syndrome displays altered messenger RNA levels in cultured fibroblasts, yet little is known of effects on transcription by RNA polymerases other than RNA polymerase II. Total RNA metabolism was examined by incubation of Hutchinson-Gilford progeria fibroblasts with [5-3H]uridine in asynchronous culture. Uptake of radiolabel was quantitative and was incorporated preferentially (99±0.3%) into newly synthesized RNA. Progeria and control cultures showed comparable rates of uptake of radiolabel, time courses of RNA synthesis, and relative intensity profiles of newly synthesized ribosomal RNA. These characteristics held over a greater than ten-fold range of cell densities (5×103 to 8×104 cells/cm2). Progeria and control fibroblasts thus have comparable metabolic capacities for uridine uptake and net RNA production, emphasizing the relative specificity of transcriptional changes previously identified in progeria cells.

Structuring factors in a marine soft bottom community during eutrophication?an experiment with radio-labelled phytodetritus

The quantitative development and uptake of radio-labelled phytodetritus in benthic macro- and meiofauna was studied in a 5-month experiment in two mesocosms, one of which received a single large nutrient (N and P) addition, while the other served as control. In reponse to the 12-fold increase in phytoplankton biomass noted after 2 weeks and the resulting enhanced accumulation of fresh phytodetritus, the abundance and biomass of the polychaetes Mediomastus ambiseta and Polydora ligni and the mud anemone Cerianthiopsis americanus increased significantly in the enriched tank. The abundances of P. ligni and M. ambiseta increased 37-fold and 12-fold, respectively, within the first two months of the experiment. No other macrofaunal or meiofaunal taxa showed any consistent positive quantitative response to the increased input of phytodetritus. In the control tank no considerable change in the benthic community structure was noted. The measurements of radio-label uptake within the benthic fauna showed that the quantitatively most successful species utilized fresh phytodetritus highly. However, a high degree of utilization of fresh detritus was also shown by taxa that did not respond quantitatively within the 5 month of the experiment, and almost all taxa showed a preference for fresh detritus over older organic material. Within the benthic meiofauna, kinorhynchs and especially foraminiferans showed a remarkably low preference for fresh detritus. A budget calculation comparing the total amounts of labelled organic carbon bound in animal tissue and in the sediment indicated that at any time at least 75% of this carbon was available for assimilation by deposit feeders. These results suggest that factors other than the availability of food, such as competition for space by a few opportunistic macrofauna species, limited the response of other species within this benthic community to the increased input of phytodetritus.

False-Positive Splenic Activity on Bone Scan

A Tc-99m MDP bone scan in a woman revealed splenic uptake of radiolabel. However, the previous (and the following) bone scan did not demonstrate this extraosseous accumulation. The finding was related to a cardiac blood pool scan the previous day, with probable splenic pooling of labeled and denatured red blood cells

Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex

Reuptake plays an important role in regulating synaptic and extracellular concentrations of glutamate. Three glutamate transporters expressed in human motor cortex, termed EAAT1, EAAT2, and EAAT3 (for excitatory amino acid transporter), have been characterized by their molecular cloning and functional expression. Each EAAT subtype mRNA was found in all human brain regions analyzed. The most prominent regional variation in message content was in cerebellum where EAAT1 expression predominated. EAAT1 and EAAT3 mRNAs were also expressed in various non-nervous tissues, whereas expression of EAAT2 was largely restricted to brain. The kinetic parameters and pharmacological characteristics of transport mediated by each EAAT subtype were determined in transfected mammalian cells by radio-label uptake and in microinjected oocytes by voltage-clamp measurements. The affinities of the EAAT subtypes for L-glutamate were similar, with Km determinations varying from 48 to 97 microM in the mammalian cell assay and from 18 to 28 microM in oocytes. Glutamate uptake inhibitors were used to compare the pharmacologies of the EAAT subtypes. The EAAT2 subtype was distinguishable from the EAAT1/EAAT3 subtypes by the potency of several inhibitors, but most notably by sensitivity to kainic acid (KA) and dihydrokainic acid (DHK). KA and DHK potently inhibited EAAT2 transport, but did not significantly affect transport by EAAT1/EAAT3. Using voltage-clamp measurements, most inhibitors were found to be substrates that elicited transport currents. In contrast, KA and DHK did not evoke currents and they were found to block EAAT2-mediated transport competitively. This selective interaction with the EAAT2 subtype could be a significant factor in KA neurotoxicity. These studies provide a foundation for understanding the role of glutamate transporters in human excitatory neurotransmission and in neuropathology.

Isolation and characterization of conditional lethal mutants of Beauveria bassiana

Temperature-sensitive mutants of Beauveria bassiana GK2016 were isolated and characterized. Heat-sensitive mutants that grew at 20 °C but not at 30 °C were generated using mutagenesis with ultraviolet light and several rounds of selection. After 2160 colonies from a heat-sensitive mutant enriched population were screened, 11 heat-sensitive strains were isolated for further study. Five mutant strains, HS1, HS2, HS6, HS9, and HS11, were stable and closely resembled the wild-type strain with respect to morphology, growth rate, and enzyme synthesis at 20 °C. Characterization of macromolecular synthesis at 30 °C using a radiolabelled precursor uptake assay indicated that three mutants, HS6, HS9, and HS11, had reduced levels of DNA, RNA, and protein synthesis at the nonpermissive temperature. Mutants affected in cell division and cell wall synthesis were characterized by microscopy. At 30 °C, mutant HS6 was defective in cellular compartmentalization and formed long, branched, aseptate mycelia that fragmented easily. Mutant HS1 was defective in cell wall biosynthesis and at 30 °C ceased to maintain cell wall integrity and lysed. Mutants HS2 and HS9 possessed temperature-sensitive lesions that could not be specified. None of the mutants were directly affected in either nuclear division or mitosis as evidenced by the accumulation of Giemsa-stainable mitotic nuclei at 30 °C. Bioassays conducted with grasshoppers showed the efficacy of the mutant strains, with the exception of HS11, to be comparable to that of the parent strain, at 20 °C. Conversely, at 32 °C the mutant strains were uninfective whereas the parental strain GK2016 was infective. It is our intention to use these strains to examine fundamental aspects of entomopathology by dissecting fungal growth and development in vitro and extending these observations to pathogenesis in insects.Key words: Beauveria bassiana, temperature-sensitive, mutants, characterization, infection.

Uptake and biodistribution of free and liposomally incorporated lipopolysaccharide of aeromonas salmonicida administered via different routes to rainbow trout: (Oncorhynchus mykiss)

AbstractThe effects on uptake and biodistribution of radiolabelled lipopolysaccharide (LPS) due to changing routes of administration, encapsulation of LPS within liposomes and altering liposomal surface charge were examined in rainbow trout (Oncorhynchus mykiss). 3H-labelled LPS, positively- and negatively-charged (14C-labelled) liposomes or 14C-labelled liposomes containing 3H-LPS were administered to trout via intravenous, intraperitoneal, intramuscular, or oral routes. Twenty-four hours following administration, relative uptake of LPS and multilamellar vesicles (MLV) based on detection of 3H and 1AC, respectively, was determined in samples taken from the kidney, spleen, liver, plasma, blood cells and skeletal muscle. In general, regardless of the route of administration, 3H-LPS, 1AC-MLV and liposomally encapsulated LPS were recovered primarily in the kidney and spleen. Intravenous administration resulted in the greatest uptake of radiolabel by the kidney and spleen, followed by the intraperitoneal and ...

Astrocytes as mediators of methylmercury neurotoxicity: effects on D-aspartate and serotonin uptake.

In this study we address the effects of methylmercuric chloride (MeHgCl), a metal that is preferentially sequestered in astrocytes, on 5-HT and glutamate/aspartate uptake by rat primary astrocyte cultures. Quantitative autoradiography (ARG) combined with glial acidic fibrillary protein (GFAP) immunocytochemistry, as well as intact-cell (bulk) measurements of radiolabel uptake of these neurotransmitters were performed in 7- and 21-day-old primary astrocyte cultures. MeHg (10 microM for 30 min) treatment of astrocytes (21 days in culture) significantly inhibited the Na(+)-dependent and fluoxetine-sensitive [3H]5-HT uptake. D-aspartate uptake in 7- and 21-day-old cultures was even more sensitive to MeHg, leading to > 99% inhibition of D-aspartate uptake by astrocytes (30 min; 10 microM MeHg). These results imply that the Na(+)-dependent and fluoxetine-sensitive 5-HT uptake, as well as the Na(+)-dependent L-glutamate/D-aspartate uptake systems in primary astrocyte cultures are sensitive to low concentrations of MeHg. Since astrocytic removal of glutamate (and aspartate) and 5-HT from the extracellular space in situ is crucial to the maintenance of chemical homeostasis, MeHg-induced uptake inhibition of 5-HT and aspartate could have cytotoxic effects on neighboring neurons.

Nature of the low activity of S-methyl-coenzyme M reductase as determined by active site titrations.

Purified S-methyl-coenzyme M reductase (methylreductase) exhibits a very low fraction of its in vivo activity, suggesting either enzyme inactivation during cell lysis and chromatographic purification or the lack of an activating component in assay mixtures. Evidence that all methylreductase molecules in the purified protein can catalyze slow substrate turnover is found in a study of turnover-dependent in vitro incorporation of radiolabeled HS-CoM at the enzyme active site (Hartzell, P. L., Donnelly, M. I., and Wolfe, R. S. (1987) J. Biol. Chem. 262, 5581-5586). We have conducted active site titrations of purified methylreductase and of a highly active partially purified preparation (Rospert, S., Bocher, R., Albracht, S. P. J., and Thauer, R. K. (1991) FEBS Lett. 291, 371-375) using the reversible competitive inhibitor bromopropanesulfonate (K(i) = 0.05 microM). Curve fitting the data based on an equilibrium binding model shows that 0.1-1.4% of purified methylreductase has functional inhibitor binding sites while up to 25% of a highly active preparation binds the inhibitor. An EPR titration of highly active methylreductase with this inhibitor is consistent with this result, showing that the MCR-red1 and -red2 EPR signals (Albracht, S. P. J., Ankel-Fuchs, D., Bocher, R., Ellermann, J., Moll, J., van der Zwann, J. W., and Thauer, R. K. (1988) Biochim. Biophys. Acta 955, 86-102) are titrated in parallel with this active fraction. Attempts to observe turnover-dependent uptake of radiolabel from [thio-35S]2-methylthioethane-sulfonate by methylreductase were unsuccessful. These results suggest that the low activity of purified methylreductase is due primarily to low percentages of catalytically competent enzyme.

Radioimmunotherapy of ovarian cancer.

Radioimmunotherapy (RIT) is a new therapeutical approach where radiolabeled monoclonal antibodies (MAb) against tumor-associated antigens are administered to treat tumor lesions. Ovarian cancer is one of the most promising fields for RIT. This paper gives an overview of some biodistribution studies in animal models and in patients with radiolabeled anti-ovarian cancer MAbs, and defines the main criteria which should be considered to plan a clinical trial of RIT in ovarian cancer. As regards the clinical results, the published outcome of various trials and the experience of the National Cancer Institute of Milan are summarized. Even if the number of patients involved in these clinical studies of RIT is too small to provide conclusive indications about its role in the management of ovarian cancer, the preliminary results from qualified groups show its potential in this disease despite the current problems that limit clinical application (above all, the instability of the radiolabeled linkage, the immunogenicity of murine antibodies, the poor absolute tumor radiolabel uptake and the bone marrow toxicity).

The influence of fluoride on proteoglycan structure using a rat odontoblast in vitro system

Using an in vitro rat incisor odontoblast system, the effect of fluoride on proteoglycans was investigated at both the metabolic and structural level. Incisors were removed from 4-week-old rats, split longitudinally, and the pulps removed. Teeth were incubated at 37 degrees C, 5% CO2 in Eagle's Minimum Essential Medium containing 35S-sulfate for 7 hours in the presence of 0 mM, 3 mM, or 6 mM sodium fluoride. Teeth were demineralized in EDTA, proteoglycan was extracted from the residue with 4 M guanidinium chloride, and further purified by anion exchange chromatography. Uptake of radiolabel was monitored by liquid scintillation counting. The resultant products were examined by cellulose acetate electrophoresis, SDS-PAGE, chondroitinase digestion, and amino acid analysis. Differential effects of fluoride were observed in both metabolism and biochemical characterization of proteoglycans following incubation at the two concentrations. Fluoride decreased uptake of the radiolabel but led to an accumulation of glycosaminoglycan within the proteoglycan of the matrix. Chondroitin sulfate was the predominant glycosaminoglycan identified, with the additional presence of dermatan sulfate and heparan sulfate identified. Dermatan sulfate levels increased in 3 mM-treated teeth. Fluoride-treated proteoglycans had a reduced molecular weight (200-90K to 180-79K); this reduction is primarily a result of smaller glycosaminoglycan chains, with limited reduction in the size of the core protein of 6 mM-treated teeth occurring. Such alterations in the biochemical metabolism and hence structure and function of proteoglycan may be implicated in the hypomineralization seen in fluorosis.

Elevated glucose alters A23187-induced release of arachidonic acid from porcine aortic endothelial cells by enhancing reacylation

Cultured porcine aortic endothelial cells were conditioned in normal (5.2 mM) and elevated (15.6 mM) glucose, prelabeled with [ 14C]arachidonic acid and stimulated with ionophore A23187. Elevated glucose cultures released less radiolabeled products and less [ 14C]arachidonic acid. Analysis of cellular lipids revealed that elevated glucose reduced net loss of radiolabel from diacylphosphatidylethanolamine, did not affect early phosphatidylinositol hydrolysis, and increased net loss from diacylphosphatidylcholine and alkenylacylphosphatidylethanolamine. Uptake of radiolabel upon stimulation was examined to measure the role of reacylation on the diminished net release of radiolabel in elevated glucose cultures. Enhanced acylation of [ 3H]arachidonic acid into cellular lipids, especially PI, was observed in stimulated and resting cultures with elevated glucose. Further, pretreatment of the cultures with an acyltransferase inhibitor, thimerosal, prior to A23187 stimulation in radiolabeled cultures, abolished the effects of glucose on eicosanoid and arachidonic acid release. Differences in the ionophore-induced net loss of radiolabel from diacylphosphatidylethanolamine and phosphatidylinositol of the two glucose treatments were diminished by thimerosal exposure, while net loss of radiolabel from diacylphosphatidylcholine and alkenylacylphosphatidylethanolamine were unaffected. The data indicate that elevated glucose alters deacylation and enhances reacylation of arachidonic acid into endothelial cells and particularly into phosphatidylinositol. Enhanced reacylation may explain some of the altered lipid pathways that have been observed in experiments that elevate glucose concentrations or involve diabetes.

Periphyton Response in an Industrial Receiving Stream: Lipid-based Physiological Stress Analysis and Pattern Recognition of Microbial Community Structure

Periphyton were collected from three physically similar sites on an industrial receiving stream which differed in their distances from the discharge. Previous studies had established that biological effects diminished with distance downstream from the discharges. In this study, a multivariate analysis of periphyton membrane lipid profiles quantitatively verified site-specific differences in time-independent microbial community structure qualitatively suggested by algal taxonomic analyses. There were no differences in periphyton abundance among sites. Periphyton physiology was evaluated using a 14C-labeled bicarbonate and 3H-labeled amino acids dual-label incubation, with subsequent analysis of carbon partitioning into lipid compartments. Total radiolabel uptake was similar for all sites. Physiological stress was shown to be highest at the site closest to the discharges using a membrane to storage lipid synthetic ratio. High values of this ratio indicated that both the phototrophic and heterotrophic constituents were stressed, and this stress declined with distance downstream. The ability to measure algal and bacterial abundance, community structure, activity, and physiological status from a single extraction provides a powerful method to evaluate periphyton which can serve as a useful biomonitoring and toxicity assessment tool for aquatic ecosystems.

Intraperitoneal therapy of malignant ascites associated with carcinoma of ovary and breast using radioiodinated monoclonal antibody 2G3

A phase I/II study of intraperitoneal (ip) radioimmunotherapy was conducted in ovarian or breast cancer patients with symptomatic chemotherapy-resistant ascites using a novel anti-mucin monoclonal antibody (mAb) 2G3 labeled with 131I. Tracer doses of 2 mCi [ 131I]2G3 were given by ip injection to 11 patients, followed by increasing therapeutic doses up to 150 mCi (cumulative) in 9 patients. There was no serious toxicity. Temporary palliation of ascites was observed in 3 of 4 patients who received doses greater than 50 mCi. Total body elimination half-life of the radiolabeled antibody assessed by gamma scintigraphy ranged from 95 to 250 hr, longer than data previously reported in patients without ascites treated with ip administered radiolabeled antibodies. However, uptake of radiolabel by tumor nodules was small and variable (2 × 10 −4 − 2 × 10 −2 % ID/g), and preferential uptake by tumor compared to normal peritoneum was observed in only 2 of 5 patients in whom biopsies were obtained. These results suggest that the observed palliation of ascites is due to prolonged retention of radiolabeled antibody in the peritoneal cavity even in the absence of specific targeting.

Effects of some nonionic polyoxyethylene surfactants on uptake of ethirimol and diclobutrazol from suspension formulations applied to wheat leaves

AbstractThe influence of a number of commercial nonionic polyoxyethylene surfactants on the foliar penetration and movement of two systemic fungicides, ethirimol and diclobutrazol, was studied in outdoor‐grown wheat plants at different growth stages and post‐treatment temperatures in two consecutive growing seasons. Both fungicides were applied as ca 0·2 μl droplets of aqueous suspension formulations containing 0·5 g litre−1 of 14C‐labelled active ingredient; surfactants were added to these suspensions at concentrations ranging from 0·2‐10 g litre−1. To achieve optimum uptake of each fungicide the use of surfactants with different physicochemical properties was required. For diclobutrazol, a lipophilic compound, uptake of radiolabel was best with surfactants of low mean molar ethylene oxide (E) content (5‐6) but it was necessary to use concentrations of ca 5 g litre−1 to attain this. The surfactant threshold concentration for uptake enhancement of radiolabel from ethirimol formulations (< 2 g litre−1) was much lower than that for diclobutrazol but surfactants with E contents > 10 induced the greatest amount of uptake. For both fungicides, surfactants with an aliphatic alcohol hydrophobe were generally more efficient in promoting their uptake than those with a nonylphenol moiety. The sorbitan‐based surfactant ‘Tween 20’ proved to be an effective adjuvant only for the ethirimol formulation; the uptake enhancing properties of the block copolymer ‘Synperonic PE/F68’ were weak. Uptake performance could not be related to the spreading properties of the respective formulations on the wheat leaf surface or to differences in solubilisation of the two fungicides by the surfactants. Although surfactants could substantially increase the amount of acropetal transport of radiolabel from both fungicides, none of those tested specifically promoted it; a constant proportion of the radioactive dose absorbed by a treated leaf was usually exported away from the site of application. The results are discussed in the light of current theories about the mode of action of surfactants as spray adjuvants.

An assay to measure the simultaneous uptake of [ 3H]dopamine and [ 14C]serotonin by the human platelet reveals an imipramine-insensitive [ 3H]dopamine uptake mechanism

To determine whether a specific dopamine uptake mechanism is present on the human platelet the simultaneous uptake of [ 3H]dopamine and [ 14C]serotonin by platelets was measured. Utilising a dual radiolabel uptake technique, platelets have been shown to take up serotonin more rapidly and to a greater extent than they take up dopamine. Furthermore, at high concentrations serotonin was able to reduce dopamine uptake by platelets by 60% whereas dopamine had no effect on serotonin uptake. Similarly, imipramine and reserpine reduced (97% and 74% respectively) serotonin uptake by platelets in a dose-dependent manner, but did not affect the uptake of dopamine. Our data show that platelets take up dopamine by a mechanism independent of the imipramine-sensitive serotonin uptake mechanism. Furthermore, the increased capacity of platelets to store serotonin is because serotonin, unlike dopamine, is transported into the dense granules of the platelet.

Radioimmunotargeting in ovarian carcinoma patients with indium-111 labeled monoclonal antibody OV-TL 3 F(ab')2: pharmacokinetics, tissue distribution, and tumor imaging.

Safety and feasibility of tumor targeting with radiolabeled monoclonal antibodies was studied in 28 patients suspected of having ovarian carcinoma, after i.v. administration of 1 mg F(ab')2 fragments of the murine monoclonal antibody OV-TL 3, labeled with 150 MBq Indium-111. There were no adverse reactions, hematological and biochemical serum parameters were stable. In one patient a (subclinical) HAMA-response was found. Plasma clearance of the immunoconjugate was biphasic with half lives of t(1/2)}alpha = 1.4+/-0.8 h and t(1/2)}beta = 25.1+/-3.7 h, resulting in an optimal time period for immunoscintigraphy at 24-48 h after administration. In 20 patients, undergoing extensive explorative surgery, a total of 271 samples of tumorous and normal tissues were analyzed for radiolabel uptake and tumor presence. The mean uptake in tumor deposits was 5.6 times (range 2.2-19.3) as high as the uptake in normal tissues (fat, peritoneum, muscle, skin). The diagnostic accuracy of immunosctigraphy was compared with that obtained with computer tomography, magnetic resonance imaging, ultrasonography and physical examination. While pelvic localizations were equally well detected by all methods, 48% of the abdominally located tumor deposits were correctly diagnosed by immunoscintigraphy, with only 12% detected by ultrasonography, 8% by CT-scanning and physical examination, and 6% by MRI. Immunoscintigraphy has potential as a diagnostic tool in ovarian cancer patients and biolocalization results justify further research into the therapeutic application of labeled monoclonal antibodies.

Evaluation of a technique for the intraoperative detection of a radiolabelled monoclonal antibody against colorectal cancer

Occult tumour deposits may be localised at operation with a radiation detecting probe following the administration of a radiolabelled monoclonal antibody (MoAb) recognising a tumour-associated antigen. We have recently evaluated the clinical usefulness of this technique in detecting primary colorectal tumours targetted with an indium-111 MoAb. In the present study the physical characteristics of the two detector systems used were investigated; a sodium iodide [NaI(Tl)] scintillation detector and a cadmium telluride (CdTe) semiconductor probe. Limitations of the technique in use have been examined by testing the statistical significance of tumour detection using an abdominal phantom based on the currently available clinical biodistribution data for tumour uptake of radiolabelled MoAbs. The effect of tumour volume, antibody uptake, collimation and counting conditions was examined. Results indicate that tumours of 10 ml volume may be detected with the NaI(Tl) probe at the lowest levels of radiolabelled antibody uptake currently reported in the literature but that at higher published levels, lesions as small as 1 ml may be identified with both detector systems. Detector sensitivity and limited antibody specificity restrict the usefulness of the technique, although moderate improvements in tumour uptake may allow the detection of tumour deposits not clinically apparent. The statistical significance criterion used for this study could be an accurate and reliable indicator for tumour detection in vivo.