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On the application of compartmental models to radioactive tracer kinetic studies of in vivo protein turnover in animals.

A mathematical framework is presented for unifying and extending the various compartmental models and formulae used to calculate fractional protein synthesis and degradation rates in animals from data obtained by infusing labelled amino acids. It is shown how the various schemes can be derived as special cases of the product-precursor model or some three-pool variant. Three-compartment representations, which circumvent the need to measure the specific radioactivity of the precursor pool, are proposed. The mathematical solutions are generally presented in a form that is amenable to parameter estimation by non-linear least squares. The problems of measuring the true precursor pool for protein synthesis are addressed, and theoretical consideration is given to assaying aminoacyl-tRNA.

Animals↗

Intraoperative lymphatic mapping and sentinel lymph node biopsy using radioactive tracer in gastric cancer.

BACKGROUND: Gastric cancer continues to be a significant health problem around the world. Surgical resection with a lymph node dissection remains the only potentially curative treatment with gastric cancer. Determination of the extent of lymph node dissection required on the basis of actual node involvement in patients with gastric cancer is important as less extensive dissection may reduce postoperative morbidity and mortality rates. The current study examines the feasibility and reliability of sentinel lymph node biopsy in gastric cancer. METHODS: A total of 32 patients who underwent gastrectomy with extended lymphadenectomy were enrolled in this study. A total volume of 148 MBq (2 mL) technetium-99m-radiolabeled, filtered sulphur colloid solution was injected into the primary lesion under gastroscopy 2 hours before the operation. Lymph nodes were examined as soon as possible by a hand-held gamma probe during the operation, without significant manipulation of the stomach or greater omentum. A sentinel lymph node (SLN) was defined by a level of radioactivity 10 times higher than the background. RESULTS: Thirty-one of 32 patients had successful SLN biopsy, with a success rate of 97%. The sensitivity, specificity, positive predictive value, and negative predictive value of SLN biopsy were 100%, 95%, 90%, and 100%, respectively. CONCLUSIONS: SLN biopsy using gamma probe in gastric cancer is a feasible procedure with high sensitivity and accuracy. This technique may be of a great benefit to surgeons in planning the extend of lymph node dissection in gastric cancer.

Aged↗

The preparation of soft gelatin capsules for a radioactive tracer study.

Clinical doses are developed for the oral coadministration of radiolabeled and nonlabeled forms of a poorly soluble investigational compound: OPC-41061. The release rates of the labeled and nonlabeled forms are equated and matched to the release rate of the polymer spray-dried form of the drug in the proposed market product. The study involves the physicochemical characterization of the powders using thermal analysis and dissolution testing, development and extemporaneous manufacture of liquid-filled soft gelatin capsules, and dissolution and stability testing of the final dosage form. Thermal analysis indicated that the labeled powder was amorphous and that the nonlabeled powder, which had been jet-milled, was crystalline. Dissolution testing of the jet-milled and spray-dried powders indicated that the former was released at a significantly slower rate. A liquid formulation containing 25% dimethyl acetamide and 75% polyethylene glycol 400 (PEG 400) solubilized the desired dose of 60 mg and exhibited a drug profile that was similar to the spray-dried formulation. The final formulation was a soft gelatin capsule containing 60 mg of drug, including 100 microCi radioactivity, dissolved in 0.8 ml of a 25% dimethyl acetamide/75% PEG 400 solution. The formulation was chemically and physically stable for a period greater than the duration of the study.

Benzazepines↗

Distribution of external cuneate nucleus afferents to the cerebellum: II. Topographical distribution and zonal pattern--an experimental study with radioactive tracers in the cat.

Small injections of tritiated leucine and the autoradiographic method were used to demonstrate efferents from restricted portions of the external cuneate nucleus (NCE) to the cerebellum. Sites of injection were analyzed by reference to the distribution of primary muscle afferents in NCE. On transverse sections, the silver deposits form longitudinal bands that, in certain regions, are packed together and label the entire surface of the granular layer; in other parts, they are separated by empty longitudinal bands. The longitudinal deposits are not continuous in the rostrocaudal direction. On the basis of the distribution of the longitudinal bands, 14 zones have been described for lobules II-VI, and 6 zones were recognized in lobules I, VIII, and the paramedian lobule. Afferents from NCE are distributed topographically. Regions of the nucleus receiving axial and neck muscles project mainly to vermal regions of lobules I-III, and to parts of lobules VIII and IX. Regions receiving afferents from forelimb muscles send their fibers preferentially to the vermian region of lobule V, to paravermian regions of lobules IV-VI, to parts of lobules VIII and IX, and to the paramedian lobule. These distributions in several respects are in agreement with the somatotopical maps of the cerebellum. However, other features support a "mosaic" arrangement: efferents from a region of NCE are distributed over several distinct sites of the cortex and efferents from different parts of the nucleus also converge to neighboring cortical regions.

Afferent Pathways↗

Calculation of residence time distributions of intravascular radioactive tracers in fields of external registration.

Because of the physiological significance of the mean velocity of blood flow, indicator dispersion models are of special interest and possess practical relevance, if biological and extraneous variables can be altered. The variables being considered are flow characteristics of the streaming blood, tracer distribution at the entrance into the flow system, and the area in which impulses are collected to form the time-activity curve. Using a simplified version of the general convective diffusion equation (diffusion model) in which the diffusion constant D includes all propagation and mixing of the tracer, a simple numerical method can be applied. The method is used to determine influences of injection and changed regions of interest on the time-activity curve and the following parameters: appearance times, peak times, mean circulation times, and the times of the first inflection points. For this purpose, the range of D was determined in 14 patients by applying experimental data to the model. The calculations on the variables show, that the advantage of this method is its applicability to any experimental case by simply adapting the input data to the recordings.

Blood Circulation↗

The extravascular pool of albumin in the non-diuretic rat kidney estimated by means of radioactive tracers and quantitative immunochemistry.

The extravascular pool of albumin in the non-diuretic rat kidney was determined as the difference between total and intravascular albumin pools. The total pool of albumin was determined in two ways in the same kideny: 1. as the distribution volume of rat endogenous albumin measured immunochemically and 2. as the distribution volume of 125I-labelled rat albumin equilibrated for 4 days. The distribution volume of 131I human albumin after 1 min equilibration was taken as a measure of the intravascular pool. Total albumin pool estimated as rat endogenous albumin volume of distribution averaged 13.4, 25.1, and 43.0 mul per 100 mg tissue in cortex, outer and inner medulla, respectively. Similar figures were obtained using 125I-labelled rat albumin. Intravascular pool of albumin in the 3 zones averaged 7.2, 19.7, and 26.8 mul per 100 mg tissue. The calculated extravascular fraction of albumin averaged 0.44, 0.21, and 0.35 for cortex, outer and inner medulla, respectively.

Albumins↗

A preliminary study of the draining lymph node basin in advanced lower rectal cancer using a radioactive tracer.

PURPOSE: This study was designed to examine the draining lymph node basin at highest risk of metastasis in lower rectal cancer using 99 mTc-tin colloid. METHODS: In 43 patients, the area with highest hot nodes density was defined as the draining lymph node basin using a gamma probe. Metastatic states of all removed lymph nodes were examined histologically. RESULTS: A total of 203 hot nodes were identified in 39 patients (91 percent) with a mean of 5.2 nodes. The number of removed lymph nodes was 808 nodes: 670 nodes in the mesorectum, and 138 nodes in the pelvis. In 21 patients, the metastatic states of 119 nodes were investigated histologically. From the distribution of the identified hot nodes, the draining lymph node basins were classified into two patterns: lateral type (n = 17), and mesorectal type (n = 22). Only 20 (17 percent) of 119 positive nodes were identified as hot node. Tumor cells that occupied the lymph node diffusely or massively probably interfered with the exact diagnosis of metastasis. Lymph node metastasis in the pelvis was observed in 5 patients (13 percent). One false negative was of the mesorectal type with diffuse metastases in the para-aortic lymph nodes. The remaining four patients were of the lateral type and all positive lymph nodes, including positive nonhot nodes, were located within the draining lymph node basin. Consequently, in 20 (95.2 percent) of 21 patients with lymph node metastasis, all positive lymph nodes were located within the draining lymph node basin of the tumor. CONCLUSIONS: Two types of the draining lymph node basin of advanced lower rectal cancer were identified using this method. The concordance between lymph node metastases and the draining lymph node basin is good.

Female↗

Single and dual labelling of cytotoxic target cells. Comparison of three radioactive tracers, [35S]methionine, [75Se]selenomethionine, and chromium-51.

[75Se]selenomethionine (75SeM) has been shown to provide several advantages over Na(2)51CrO4 (51Cr) labelling of metabolizing target cells: high labelling efficiency and low spontaneous release of 75SeM-labelled target cells permit improved monitoring of cytotoxicity due to extended effector/target ratios in short- and long-term assays. Unfortunately, 75SeM will soon be difficult to obtain. Therefore we studied the suitability of [35S]methionine (35SM) as a substitute for 75SeM. Furthermore, we explored the potential of dual labelling of suspension target cells applying combinations of 35SM and 51Cr or 75SeM and 51Cr. 35SM is a suitable substitute for 75SeM retaining most of the advantages of 75SeM labelling. Although considerably higher labelling of cells is possible we obtained the most efficient labelling with 100-400 kBq/ml of 35SM or 75SeM resulting in a relatively high uptake (3-15 cpm/cell) and very low spontaneous release (1-2%/h) up to 24 h. This permits short- and long-term cytotoxic assays and the use of low numbers of target cells (1 x 10(3)) providing increased cytotoxic sensitivity with reduced amounts of effector cells. Suitable dual labelling of target cells with 35SM plus 51Cr or 75SeM plus 51Cr documented convincingly identical release kinetics for 35SM and 75SeM but partially discordant ones for 51Cr. Depending on the target cell used dual labelling permits discrimination and monitoring of different cytotoxic or release mechanisms in cellular cytotoxicity.

Chromium Radioisotopes↗