Levels Of Tracer Research Articles

Gamma-ray spectra of post-irradiated uranium salt for total mass accounting with sodium-22 tracer

In order to meet the safeguard requirements for Nuclear Material Control and Accountability (MC&A) in liquid-fueled molten salt reactors, fuel salt transportation, and fuel cycle processes, it is important to develop effective methods for measuring and monitoring the mass of molten fuel salt or coolant salt. This paper seeks to validate the radioactive tracer dilution (RTD) method used for determining the mass of irradiated uranium-bearing molten salt. Small scale testing was conducted for this method by irradiating 6.065 g of MgCl–KCl–UCl3 salt mixture with 1.21 mg of 235U at The Ohio State University, resulting in a neutron fluence of 4.0 × 1016 n/cm2. Gamma spectra were acquired over the course of a 42-day period starting in March 2023 to assess fission products and activity levels of the 22Na tracer that was added before irradiation. No additional interference peaks were observed to overlap with the 1274.54 keV energy peak from 22Na, aside from the known 154Eu peaks, which can be corrected based on prior studies. By placing a thin piece of lead between the source and detector, deadtime was effectively reduced while still allowing observation of the higher-energy peaks, most notably around the 154Eu peak at 1004.76 keV used for interference correction. Overall, the uranium salt irradiation techniques applied in this experiment demonstrate the potential of the RTD method to effectively measure small irradiated samples for large scale molten fuel salt applications.

Evaluation of Chelator-to-Antibody Ratio on Development of 89Zr-iPET Tracer for Imaging of PD-L1 Expression on Tumor.

89Zr-iPET has been widely used for preclinical and clinical immunotherapy studies to predict patient stratification or evaluate therapeutic efficacy. In this study, we prepared and evaluated 89Zr-DFO-anti-PD-L1-mAb tracers with varying chelator-to-antibody ratios (CARs), including 89Zr-DFO-anti-PD-L1-mAb_3X (tracer_3X), 89Zr-DFO-anti-PD-L1-mAb_10X (tracer_10X), and 89Zr-DFO-anti-PD-L1-mAb_20X (tracer_20X). The DFO-anti-PD-L1-mAb conjugates with varying CARs were prepared using a random conjugation method and then subjected to quality control. The conjugates were radiolabeled with 89Zr and evaluated in a PD-L1-expressing CT26 tumor-bearing mouse model. Next, iPET imaging, biodistribution, pharmacokinetics, and ex vivo pathological and immunohistochemical examinations were conducted. LC-MS analysis revealed that DFO-anti-PD-L1-mAb conjugates were prepared with CARs ranging from 0.4 to 2.0. Radiochemical purity for all tracer groups was >99% after purification. The specific activity levels of tracer_3X, tracer_10X, and tracer_20X were 2.2 ± 0.6, 8.2 ± 0.6, and 10.5 ± 1.6 μCi/μg, respectively. 89Zr-iPET imaging showed evident tumor uptake in all tracer groups and reached the maximum uptake value at 24 h postinjection (p.i.). Biodistribution data at 168 h p.i. revealed that the tumor-to-liver, tumor-to-muscle, and tumor-to-blood uptake ratios for tracer_3X, tracer_10X, and tracer_20X were 0.46 ± 0.14, 0.58 ± 0.33, and 1.54 ± 0.51; 4.7 ± 1.3, 7.1 ± 3.9, and 14.7 ± 1.1; and 13.1 ± 5.8, 19.4 ± 13.8, and 41.3 ± 10.6, respectively. Significant differences were observed between tracer_3X and tracer_20X in the aforementioned uptake ratios at 168 h p.i. The mean residence time and elimination half-life for tracer_3X, tracer_10X, and tracer_20X were 25.4 ± 4.9, 24.2 ± 6.1, and 25.8 ± 3.3 h and 11.8 ± 0.5, 11.1 ± 0.7, and 11.7 ± 0.6 h, respectively. No statistical differences were found between-tracer in the aforementioned pharmacokinetic parameters. In conclusion, 89Zr-DFO-anti-PD-L1-mAb tracers with a CAR of 1.4-2.0 may be better at imaging PD-L1 expression in tumors than are traditional low-CAR 89Zr-iPET tracers.

Cervical catheter placement leads to improved rostral distribution of a radiolabeled 18F-baclofen analog in cynomolgus monkeys

BackgroundIntrathecal (IT) catheter delivery of baclofen via continuous infusion using an implantable pump is an important means of treating patients with severe spasticity. We evaluated the impact of IT catheter tip placement (upper vs. lower) on brain and spine distribution of a radioactive tracer molecule.MethodsCynomolgus monkeys were implanted with an IT catheter, with the distal tip located at either C1 or T10 and attached to an implanted continuous infusion pump. A radioactive tracer molecule, an 18F-baclofen analog, and PET imaging were utilized to observe tracer distribution and quantitate levels of tracer in both the brain and spine according to catheter tip location.ResultsIt was consistently determined that a high cervical (C1) catheter tip placement resulted in both more rapid distribution and higher concentrations of radiotracer in the brain and upper spine compared with lower thoracic (T10) during the first 6 hours of infusion.ConclusionsThese results indicate that delivery of 18F-baclofen by IT catheter results in repeatable proportional distribution within regions of the brain and spine. The data also suggest that the greatest exposure to the brain and cervical spinal cord occurs when the catheter tip is located at the first cervical vertebra.

Adapted tracer gas test for passive measurement of total air change rates using alternative tracer substance

This paper describes the development of a new adaptation of the traditional tracer gas test (TGT) used for total air change rates (ACH) measurement. This adapted TGT, based on constant tracer injection, is intended for use in large-scale IAQ assessments and employs an alternative tracer gas that is more adequate than the currently employed SF6 and perfluorocarbons, and that can be co-captured and co-analyzed with commonly assessed VOCs by commercial passive IAQ-sampling. As it is based on passive sampling, the proposed TGT yields long-term integrated ACH values, and is thus indicated only for studies focused on characterizations based on average estimations rather than on analyses requiring fine temporal resolution. By means of literature study and lab experiments, decane-D22 was selected as a suitable tracer substance. The selected tracer was shown not to adhere/absorb significantly to surfaces. A passive source of decane-D22 was selected and optimized in lab, providing stable and repeatable emission rates unaffected by varying RH and ACH. An exponential prediction curve was derived for determining the source emission rate from the average room temperature. Moreover, a range of adequate levels of liquid tracer inside the source is suggested. A successful field test application for validation of the new TGT is also described.

Upregulation of cannabinoid receptor type 2, but not TSPO, in senescence-accelerated neuroinflammation in mice: a positron emission tomography study

BackgroundMicroglial cells are activated in response to changes in brain homeostasis during aging, dementia, and stroke. Type 2 endocannabinoid receptors (CB2) and translocator protein 18 kD (TSPO) are considered to reflect distinct aspects of microglia-related neuroinflammatory responses in the brain. CB2 activation is considered to relate to the neuroprotective responses that may occur predominantly in the early stage of brain disorders such as Alzheimer’s disease, while an increase in TSPO expression tends to occur later during neuroinflammation, in a proinflammatory fashion. However, this information was deduced from studies with different animal samples under different experimental settings. In this study, we aimed to examine the early microglial status in the inflammation occurring in the brains of senescence-accelerated mouse prone 10 (SAMP10) mice, using positron emission tomography (PET) with CB2 and TSPO tracers, together with immunohistochemistry.MethodsFive- and 15-week-old SAMP10 mice that undergo neurodegeneration after 7 months of age were used. The binding levels of the TSPO tracer (R)-[11C]PK11195 and CB2 tracer [11C]NE40 were measured using PET in combination with immunohistochemistry for CB2 and TSPO. To our knowledge, this is the first study to report PET data for CB2 and TSPO at the early stage of cognitive impairment in an animal model.ResultsThe standard uptake value ratios (SUVRs) of [11C]NE40 binding were significantly higher than those of (R)-[11C]PK11195 binding in the cerebral cortical region at 15 weeks of age. At 5 weeks of age, the [11C]NE40 SUVR tended to be higher than the (R)-[11C]PK11195 SUVR. The (R)-[11C]PK11195 SUVR did not significantly differ between 5- and 15-week-old mice. Consistently, immunostaining analysis confirmed the upregulation of CB2, but not TSPO.ConclusionsThe use of the CB2 tracer [11C]NE40 and/or an immunohistochemical approach allows evaluation of the role of microglia in acute neuroinflammatory processes in the early stage of neurodegeneration. The present results provide in vivo evidence of different responses of two types of microglia to senescence-accelerated neuroinflammation, implying the perturbation of microglial balance by aging. Specific treatment for CB2-positive microglia might help ameliorate senescence-related neuroinflammation and the following neurodegeneration.

In vivo TSPO and cannabinoid receptor type 2 availability early in post-stroke neuroinflammation in rats: a positron emission tomography study

BackgroundUpregulated levels of 18-kDa translocator proteins (TSPO) and type 2 endocannabinoid receptors (CB2) are considered to reflect different aspects of microglia-related neuroinflammatory responses in the brain. Relative to the increase in the TSPO expression that occurs slightly later during neuroinflammation in a proinflammatory fashion, CB2 activation is considered to relate to the neuroprotective responses that occurs predominantly at an early stage of brain disorders. These findings, however, were deduced from studies with different animal samples under different experimental settings. Here, we aimed to examined the differences in TSPO binding and CB2 availability at an early stage of stroke in the same animal using positron emission tomography (PET).MethodsWe used a total of eight Sprague-Dawley rats that underwent photothrombotic stroke surgery. The binding levels of a TSPO tracer [11C](R)PK11195 and a CB2 tracer [11C]NE40 were measured at 24 h after the surgery in the same animal using PET in combination with immunohistochemistry for CB2 and several other markers. A morphological inspection was also performed with X-ray computed tomography for small animals.ResultsThe levels of [11C]NE40 binding potential (BPND) were significantly higher in the cerebral cortical region on the lesion side than those on the non-lesion side, whereas no difference was found in the levels of [11C](R)PK11195 BPND between hemispheres. The tracer influx index (R1) data were all reduced on the lesion side irrespective of tracers. This increase in [11C]NE40 BPND was concomitant with an elevation in CB2 expression mainly within the microglia in the peri-infarct area, as shown by immunohistochemical examinations with Iba-1, CD11b/c+, and NG2+ staining.ConclusionsThe present results provide in vivo evidence of different responses of microglia occurring in the acute state of stroke. The use of the CB2 tracer [11C]NE40 allows us to evaluate the roles played by the neuroprotective aspect of microglia in acute neuroinflammatory processes.

Ultra Staging to Unmask the Prescribing of Adjuvant Therapy in Cancer Patients: The Future Opportunity to Image Micrometastases Using Total-Body 18F-FDG PET Scanning

Ultra Staging to Unmask the Prescribing of Adjuvant Therapy in Cancer Patients: The Future Opportunity to Image Micrometastases Using Total-Body ¹⁸F-FDG PET Scanning

Glutathione PEGylated liposomes: pharmacokinetics and delivery of cargo across the blood–brain barrier in rats

Partly due to poor blood–brain barrier drug penetration the treatment options for many brain diseases are limited. To safely enhance drug delivery to the brain, glutathione PEGylated liposomes (G-Technology®) were developed. In this study, in rats, we compared the pharmacokinetics and organ distribution of GSH-PEG liposomes using an autoquenched fluorescent tracer after intraperitoneal administration and intravenous administration. Although the appearance of liposomes in the circulation was much slower after intraperitoneal administration, comparable maximum levels of long circulating liposomes were found between 4 and 24 h after injection. Furthermore, 24 h after injection a similar tissue distribution was found. To investigate the effect of GSH coating on brain delivery in vitro uptake studies in rat brain endothelial cells (RBE4) and an in vivo brain microdialysis study in rats were used. Significantly more fluorescent tracer was found in RBE4 cell homogenates incubated with GSH-PEG liposomes compared to non-targeted PEG liposomes (1.8-fold, p < 0.001). In the microdialysis study 4-fold higher (p < 0.001) brain levels of fluorescent tracer were found after intravenous injection of GSH-PEG liposomes compared with PEG control liposomes. The results support further investigation into the versatility of GSH-PEG liposomes for enhanced drug delivery to the brain within a tolerable therapeutic window.

Metabolism of Epidermal Growth Factor Receptor Targeting Probe [11C]PD153035: Impact on Biodistribution and Tumor Uptake in Rats

Several tracers have been evaluated as probes for noninvasive epidermal growth factor receptor (EGFR) quantification with PET. One of the most promising candidates is the (11)C-labeled analog of the EGFR tyrosine kinase inhibitor PD153035. However, previous in vitro studies indicated extensive metabolism of the tracer, which could be disadvantageous for the assessment of receptor density in vivo. The aim of this study was to investigate the in vivo metabolism of [(11)C]PD153035 to determine whether alterations in metabolite formation are accompanied by changes in biodistribution and tumor uptake. EGFR-overexpressing human epidermoid carcinoma xenografts in rats were used in all examinations of tumor uptake. Cytochrome P450 enzymes of subfamilies CYP2D and CYP3A were inhibited before intravenous injection of [(11)C]PD153035 into healthy and tumor-bearing male rats. Samples were taken from arterial blood and urine, and the occurrence of radioactive metabolites was assessed with radio-high-performance liquid chromatography. Dynamic PET examinations of healthy and tumor-bearing animals were performed. In 1 rat, the effect of local intraarterial administration was examined. [(11)C]PD153035 labeled at position 6 was metabolized extensively in vivo in male rats, resulting in very low levels of the intact tracer in plasma only minutes after injection. The major identified radiolabeled metabolites found were the N-oxide and metabolites arising from O demethylation at position 7. They were reduced by inhibition of CYP2D and CYP3A enzymes. PET revealed enzyme activity-dependent changes in the radioactivity distribution in the liver and tumors. Local administration of [(11)C]PD153035 greatly increased radioactivity levels in the adjacent tumor compared with levels typically found after intravenous administration. The highest tumor-to-muscle ratio at 60 min after intravenous injection was found in the untreated animals, whereas the overall highest ratio was found in the tumor near the intraarterial administration site. We suggest that the metabolism of [(11)C]PD153035 should be taken into consideration when this tracer is used to quantify EGFR expression, as our results indicated that the distribution of radioactivity to EGFR-overexpressing tumors was affected by the rate of metabolism and the route of administration.

A new 15N tracer method to determine N turnover and denitrification of Pseudomonas stutzeri

Although denitrification is one of the key processes of ecosystem N turnover, the understanding of the regulation of the denitrification pathway is still limited due to the lack of feasible methods for the quantification of N2 formation. Based on the previously developed isotope pairing method, we present a new in vitro 15N tracer method for the quantification of N2 released from denitrification by bacterial cultures. The application of the new method was enabled by replacing the background air in the sample flasks with a gas mixture of He and O2 with an approximately 50-fold reduced N2 background (1.7% v/v), allowing for a direct and sensitive quantification of N2 formation with isotope-ratio mass spectrometry after 15N-labelling on the one hand, but leaving the method relatively insensitive to intrusion of ambient N2 on the other hand. The method was tested on bacterial cultures of Pseudomonas stutzeri grown at different oxygen levels. Additionally, NO and N2O formation were determined with a chemoluminescence analyser and a gas chromatograph, respectively. Following labelling with 15N-ammonium and 15N-nitrate, it could be shown that P. stutzeri used ammonium preferably for biomass build-up, and nitrate preferably as electron acceptor. Between 84–107% of the total available N could be recovered. Due to the high sensitivity of the new method only low levels of 15N tracer were necessary, minimising substrate-induced effects and making this method also an appropriate tool for the use on soil cores. By that it offers a new method for studying denitrification in terrestrial ecosystems.

Small Amounts of Zinc from Zinc Oxide Particles in Sunscreens Applied Outdoors Are Absorbed through Human Skin

Metal oxide nanoparticles are commonly used in personal-care formulations as protective agents against exposure to ultraviolet radiation. Although previous research has concluded that nanoparticles do not penetrate healthy skin, it remains contentious whether this conclusion holds under normal conditions of sunscreen use. Humans (n = 20) were exposed to sunscreens containing zinc oxide (ZnO) particles to determine if Zn from the particles was absorbed through skin over five consecutive days under outdoor conditions. Two sunscreens were tested-"nano sunscreen" containing 19-nm nanoparticles and "bulk sunscreen" containing > 100-nm particles. Venous blood and urine samples were collected 8 days before exposure, twice daily during the trial, and 6 days post-exposure. As the first application in nanotechnology studies, stable isotope tracing was used where the ZnO, enriched to > 99% with the stable isotope (68)Zn, allowed dermally absorbed zinc to be distinguished from naturally occurring zinc. The overwhelming majority of applied (68)Zn was not absorbed, although blood and urine samples from all subjects exhibited small increases in levels of tracer (68)Zn. The amount of tracer detected in blood after the 5-day application period was ∼1/1000 th that of total Zn in the blood compartment. Tracer levels in blood continued to increase beyond the 5-day application phase in contrast to those in urine. Levels of (68)Zn in blood and urine from females receiving the nano sunscreen appeared to be higher than males receiving the same treatment and higher than all subjects receiving the bulk sunscreen. It is not known whether (68)Zn has been absorbed as ZnO particles or soluble Zn or both.

Lymphedema Development and Lymphatic Function following Lymph Node Excision in Sheep

Background: Our objective was to develop an animal model of postsurgical lymphedema that would permit quantitation of edema and lymphatic function after the removal of a single popliteal lymph node in sheep. Methods: As a measure of lymph transport, ¹²⁵I-human serum albumin was injected into prenodal vessels at 8, 12 and 16 weeks after nodal excision, and plasma levels of the protein tracer were used to calculate the transport rate of the tracer to blood (percent injected per hour). Edema was quantified from the circumferential measurement of the hind limbs. Results and Conclusions: Following nodal excision, the limbs became progressively more edematous up to 3 days after nodectomy. After this, the swelling decreased but had not resolved even at 16 weeks after surgery. Compared with control limbs (17.2 ± 0.6; n = 7), lymphatic function was depressed at 8 weeks after surgery (10.6 ± 1.5; n = 7). At 12 (14.4 ± 1.0; n = 7) and 16 weeks (13.9 ± 1.0; n = 6), regeneration of lymphatic vessels at the excision site helped to restore about 80% of lymphatic capacity. These techniques may be helpful in understanding the pathophysiology associated with cancer-related postsurgical lymphedema and may facilitate the development of new strategies to treat or prevent this condition.

Increasing the radiochemical purity of 99mTc-sestamibi commercial preparations results in improved sensitivity of dual-phase planar parathyroid scintigraphy

BACKGROUND Poor results for dual-phase parathyroid scintigraphy have recently prompted increased use of dual-tracer imaging. We noticed that seminal studies used higher radiochemical purity than provided by current commercial preparations meeting US Pharmacopea (USP) specifications (90% of technetium bound to sestamibi). We surmised that the presence of unbound Tc (non-MIBI tracer) might hamper dual-phase detection that is dependent on rapid wash-out of technetium from thyroid tissue. PURPOSE To test the hypothesis that reducing non-MIBI tracer will enhance thyroid wash-out and improve sensitivity of dual-phase imaging. METHODS Starting in April 2003 we decreased the technetium to sestamibi ratio. This resulted in a significant decrease of non-MIBI tracer from 8.1+/-2.2% (SD) (group 1, n = 42) to 3.5+/-1.1% (group 2, n = 47) (P < 0.05 t-test). We performed a retrospective review of 89 patients with primary hyperparathyroidism who underwent imaging and subsequent surgery. The pathological findings served as the 'gold standard'. RESULTS Scanning detected 21/39 diseased glands (sensitivity=54%) in group 1 patients. In group 2 imaging detected 38/45 diseased glands (sensitivity = 84%). An improvement in sensitivity (P < 0.01) was achieved by modifying the radiopharmaceutical preparation. CONCLUSIONS Elevated levels of non-MIBI tracer in Tc-MIBI commercial preparations result in persistent thyroid background activity that may interfere with detection of parathyroid pathology. Achieving a higher degree of radiochemical purity (at least 95% bound, 5% impurities) than required by USP may be needed for optimal results. The large variation in sensitivity reported in the literature may be related in part to non-uniform radiopharmaceutical preparation.

Increasing the radiochemical purity of 99mTc sestamibi commercial preparations results in improved sensitivity of dual-phase planar parathyroid scintigraphy

Poor results for dual-phase parathyroid scintigraphy have recently prompted increased use of dual-tracer imaging. We noticed that seminal studies used higher radiochemical purity than provided by current commercial preparations meeting US Pharmacopea (USP) specifications (90% of technetium bound to sestamibi). We surmised that the presence of unbound Tc (non-MIBI tracer) might hamper dual-phase detection that is dependent on rapid wash-out of technetium from thyroid tissue. To test the hypothesis that reducing non-MIBI tracer will enhance thyroid wash-out and improve sensitivity of dual-phase imaging. Starting in April 2003 we decreased the technetium to sestamibi ratio. This resulted in a significant decrease of non-MIBI tracer from 8.1+/-2.2% (SD) (group 1, n = 42) to 3.5+/-1.1% (group 2, n = 47) (P < 0.05 t-test). We performed a retrospective review of 89 patients with primary hyperparathyroidism who underwent imaging and subsequent surgery. The pathological findings served as the 'gold standard'. Scanning detected 21/39 diseased glands (sensitivity=54%) in group 1 patients. In group 2 imaging detected 38/45 diseased glands (sensitivity = 84%). An improvement in sensitivity (P < 0.01) was achieved by modifying the radiopharmaceutical preparation. Elevated levels of non-MIBI tracer in Tc-MIBI commercial preparations result in persistent thyroid background activity that may interfere with detection of parathyroid pathology. Achieving a higher degree of radiochemical purity (at least 95% bound, 5% impurities) than required by USP may be needed for optimal results. The large variation in sensitivity reported in the literature may be related in part to non-uniform radiopharmaceutical preparation.

The Effects of CaNa2EDTA on Brain Lead Mobilization in Rodents Determined Using a Stable Lead Isotope Tracer

Studies have demonstrated the efficacy of CaNa2EDTA for reducing lead (Pb) levels in blood and soft tissues, including brain. However, a concern remains that a single dose of CaNa2EDTA may cause a significant increase in brain Pb levels due to a redistribution of endogenous Pb. Here we utilized a rodent model of Pb exposure in combination with a sensitive stable Pb isotope tracer methodology to assess the effects of CaNa2EDTA chelation treatment on the redistribution of Pb in brain, blood, kidney, and bone tissues. Thirty-two adult female albino rats (n = 6–7 animals/group) were exposed to 100 μg Pb/mL in drinking water for 4 weeks. Stable 204Pb tracer was administered via i.p. injection over 2 days prior to chelation. CaNa2EDTA was administered i.p. at a dose of 150 mg/kg/day for 1 to 5 days. Statistical differences were evaluated with univariate ANOVA. Under the Pb exposure and chelation treatment regimens utilized here, there was no evidence of a measurable redistribution of endogenous Pb (as total Pb or labile 204Pb tracer) into the brain after a single CaNa2EDTA dose. Further, CaNa2EDTA was not efficacious in measurably reducing brain or bone Pb levels, although brain levels of labile 204Pb tracer were significantly reduced after 5 days of chelation. CaNa2EDTA treatment was effective in significantly reducing both blood and kidney Pb levels. Overall, these data substantiate the efficacy of CaNa2EDTA for reducing soft tissue Pb levels, but not total brain Pb, and they do not support concern for a transient increase in brain Pb levels with treatment.

Gamma scintigraphy of the biodistribution of 123I-labelled N-(2-hydroxypropyl)methacrylamide copolymer-doxorubicin conjugates in mice with transplanted melanoma and mammary carcinoma.

An N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-doxorubicin conjugate is currently under clinical evaluation as a new antitumour agent. It has been shown previously that such conjugates exhibit selective tumour accumulation. In this study HPMA copolymer doxorubicin conjugates of low (LMW) or high (HMW) molecular weight were synthesised (which had a weight average molecular weight (Mw) of 25,000 and 94,000 respectively) and additionally contained a small amount (1 mol%) of the comonomer methacryloyltyrosinamide to permit labelling with [123I or 125I]iodide. Gamma camera imaging using the 123I-labelled probes was used to follow time-dependent biodistribution after intraperitoneal (i.p.) or intravenous (i.v.) administration to mice bearing subcutaneously either B16F10 melanoma or a mammary carcinoma. Imaging showed more rapid clearance of LMW conjugate from the peritoneal cavity than HMW conjugate. The images of mice given the LMW conjugate revealed rapid urinary excretion of radioactivity after both i.p. and i.v. injection with an early high concentration of tracer in the bladder, and subsequently a very high concentration in the kidneys, which came to dominate the views. Dissection analysis 2 days after administration of the LMW conjugate revealed a kidney level of radioactivity corresponding to 25-40% dose/g tissue in mice bearing the two tumour models. Following administration of the HMW conjugate kidney accumulation at 2 days was less due to retention of the higher molecular weight polymer molecules in the circulation, and spleen and liver displayed the highest concentrations of radioactivity. The tumour accumulation of LMW and HMW conjugates was; mammary carcinoma 3.18 and 5.29% dose/g respectively; B16F10 melanoma 3.23 and 8.82 %dose/g although these levels of tracer enabled visualisation in the images of the mammary carcinoma with HMW conjugate at later time points. The smaller size of the B16F10 tumour masses did not permit clear visualisation.

Evidence for a Membrane Exchangeable Glucose Pool in the Functioning of Rat Liver Glucose-6-phosphatase

We have investigated the kinetics of tracer uptake into rat liver microsomes in relation to [14C]glucose 6-phosphate (Glu-6-P) hydrolysis by glucose 6-phosphatase (Glu-6-Pase). 1) The steady-state levels of intravesicular tracer accumulated during the rapid (AMP1) and slow (AMP2) phases of uptake both demonstrate Michaelis-Menten kinetics relative to outside Glu-6-P concentrations with Km values similar to those observed for the initial burst (Vi) and steady-state (VSS) rates of Glu-6-P hydrolysis. 2) The AMP1/AMP2 ratio is constant (mean value = 0.105 +/- 0.018) over the whole range of outside Glu-6-P concentrations and is equal to the AMP1max/AMP2max ratio (0.109 +/- 0.032). 3) Linear relationships are observed between the initial rates of glucose transport during the slow uptake phase (V alpha 2) and [AMP1], and between [VSS] and [AMP2]. 4) The value of Vss max exceeds by more than 10-fold that of V alpha 2 max. 5) It is concluded that the substrate transport model is incompatible with those results and that AMP1 represents a membrane exchangeable glucose pool. 6) We propose a new version of the conformational model in which the catalytic site lies deep within a hydrophilic pocket of an intrinsic membrane protein and communicates with the extra- and intravesicular spaces through channels with different glucose permeabilities.

Application of fluorescence densitometry to the study of net albumin uptake by the rabbit aortic wall up- and downstream of intercostal ostia

A method was developed for measuring levels of lissamine rhodamine B-labelled albumin in arterial walls with a spatial resolution of ca. l μm 3. The method was used to study variation in net macromolecular uptake up- and downstream of intercostal ostia in a small number of rabbit aortae. The physical and biological properties of the fluorescent tracer, including its stability, were compatible with its use in vivo. Tracer was injected into the ear vein of conscious rabbits. After 3 h the rabbits were anaesthetized and the thoracic aorta was fixed in situ at physiological pressure. The vessel was embedded in epoxy resin and longitudinal sections of the aortic wall were cut through the centre of the intercostal ostia. Photomicrographs were used to record fluorescence from these sections. The optical density across the photomicrographs was measured and related to the distribution of tracer in the wall. Mean intima-medial levels of tracer were greater downstream of ostia than upstream but were lower near the flow divider than further downstream. Higher levels of tracer were found in the adventitia than in the media and, in the latter, the distribution appeared to be related to the lamellar structure

Iodine-131 and indium-111 labelled avidin and streptavidin for pre-targetted immunoscintigraphy with biotinylated anti-tumour monoclonal antibody.

Studies have been carried out in mice to examine by gamma camera imaging and dissection analysis the biodistribution of 131I- and 111In-labelled avidin and streptavidin. This has included mice with human tumour xenografts pre-targetted with biotinylated anti-tumour monoclonal antibody. Both iodine-labelled avidin and streptavidin were cleared rapidly from the circulation particularly to kidneys, which showed prolonged retention of the tracer. Similar distribution was seen with 111In-labelled preparations, although here tracer also accumulated in the liver. Radiolabelled preparations could form complexes in vitro with a biotinylated monoclonal antibody. This biotinylated antibody, following radioiodine labelling, localized in xenografts of a human osteosarcoma. When xenografted mice were injected with biotinylated antibody followed by 111In-labelled avidin, levels of tracer per gram of tumour tissue were four times higher than those in non-pretreated mice. However, there was still marked liver and kidney uptake of tracer and, since this dominated the images, tumours were not visualized by scintigraphy.

Food iron and lead absorption in humans

Food iron and lead absorption were measured simultaneously in 28 subjects by extrinsically labeling three consecutive meals with the radioactive tracers, iron 59-sulfate and lead 203-chloride. Absorption was measured directly in all subjects by whole-body counting and indirectly in 15 subjects by assessing subsequent levels of tracer in blood. Iron status of the subjects ranged from iron deficient to replete, thus providing a wide range of iron absorption.Statistically significant positive correlations were obtained between food-iron and lead absorption measured by whole-body counting and also between the tracer levels of iron and lead in the blood. However, the correlation between the absorption of the two elements was not strong, as evidenced by the fact that only 50% of the subjects who hyperabsorbed iron also hyperabsorbed lead.