Paul Wyeth

New approach to the localisation of phaeochromocytoma: imaging with iodine-131-meta-iodobenzylguanidine.

Thirty eight patients with known or suspected phaeochromocytoma were studied by radioisotope imaging after intravenous administration of iodine-131-meta- iodobenzylguanidine (131I- mIBG ), a radiopharmaceutical which has affinity for chromaffin tumours. Seventeen positive results (including one false positive) and 21 negative results (including two false negatives) were obtained. Clinical accuracy was 92%. Urinary noradrenaline concentrations were raised in all patients with confirmed phaeochromocytoma. These findings show that 131I- mIBG is of value in localising and assessing the extent of chromaffin tumours.

Correlation of zinc distribution and enhanced hardness in the mandibular cuticle of the leaf-cutting ant Atta sexdens rubropilosa.

The mandibular mouthparts of a variety of arthropods have been shown to contain significant amounts of zinc (Smith et aI. 1992). The metal appears to be localised to the cutting edges, where the cuticle is substantially harder than other regions. Here, we show that there is a correlation between the distribution of zinc and the mechanical properties of the mandibles of the leaf-cutting ant Atta sexdens rubropilosa. X-ray mapping showed the localisation of zinc to the teeth of the cutting edges which were found to be up to three times as hard as the non-replete cuticle.

The comparison of 8-hydroxyquinoline, tropolone, and acetylacetone as mediators in the labelling of polymorphonuclear leucocytes with indium-111: a functional study.

Tropolone forms a lipophilic complex with indium-111 which is capable of mediating the labelling of polymorphonuclear leucocytes (PMNs) by this isotope; labelling efficiencies are comparable with the best achieved using 8-hydroxyquinoline and acetylacetone. However, in terms of PMN chemotaxis and phagocytosis, tropolone is significantly less toxic than either of the other ligands. 8-Hydroxyquinoline was found to reduce PMN chemotaxis and phagocytosis to approximately 70% of the control values at a concentration of 20 μM. Tropolone may prove a superior labelling reagent.

Radioiodinated iodobenzylguanidines for diagnosis and therapy

Radiolabelled meta-iodobenzylguanidine has been one of the most successful of recent radiopharmaceuticals. In the short period of five years it has been shown to have high diagnostic sensitivity and specificity for many tumours of neuroectodermal origin. Furthermore its excellent concentration in many malignant tumours of this type offers a novel alternative treatment to those available at present.

CUTICULAR METALS: QUANTIFICATION AND MAPPING BY COMPLEMENTARY TECHNIQUES

Metal‐replete cuticle was characterised by back‐scattered electron imaging, secondary ion mass spectrometry, proton induced X‐ray emission and SEM‐X‐ray microanalysis. Each technique was found to have singular advantages and limitations for localising and quantifying metal content. Manganese and zinc were found coincident at the mandibular cutting edge of the leaf‐cutting ant Atta sexdens; these two metals were found in different zones within jaws of the ragworm, Nereis virens; while only manganese was found in the jaws of the termite C. cumulans.

The enzyme-inhibitor approach to cell-selective labelling—I. Sulphonamide inhibitors of carbonic anhydrase as carriers for red cell labelling: in vitro uptake of pIBS by human red blood cells

Red cell carbonic anhydrase is identified as an ideal target in an enzyme-inhibitor approach to radiolabel localisation. Current problems in blood pool labelling could be overcome by using selective sulphonamide inhibitors as carriers. p-Iodobenzenesulphonamide (pIBS) was selected as the choice reagent for red blood cell labelling. Rapid uptake of [125I]-pIBS was found in vitro, consistent with passive diffusion across the cell membrane. The intracellular binding could be attributed to interaction with two specific acceptor sites, with dissociation constants of 4.9 +/- 1.0 and 0.10 +/- 0.05 mumol dm-3, and maximum binding capacities of 166 +/- 5 and 19.9 +/- 1.0 mumol dm-3, respectively under the experimental conditions. These data correlate with the two major carbonic anhydrase isozymes; acceptor assignments were confirmed by gel chromatography of the red cell lysate.

Lymphocyte labelling with indium: Cytotoxicity studies

Viability studies on lymphocytes labelled with indium In111 using oxine as a ligand showed impairment as measured by trypan-blue assessment and rosetting ability. In addition, lymphocyte response to phytohaemagglutinin stimulation as measured by tritiated-thymidine uptake was also impaired at levels where adequate cell labelling had taken place. Cadmium toxicity was not noticed, and the use of tropolone as a ligand offered possibilities of reduced cellular toxicity. Such cytotoxicity may not have been important in earlier reported studies on granulocytes where the large numbers available for in vivo work and the short periods of study still allowed useful conclusions to be drawn. However, because of the prolonged lifespan of the human lymphocyte, the cytotoxic effects of the processing might well make the long-term studies which would be of interest much less reliable for clinical assessment.

The Enzyme-Inhibitor Approach to Cell-Selective Labelling. III. Sulphonamide Inhibitors of Carbonic Anhydrase as Carriers for Red Cell Labelling

Selective radiolabelling of red blood cells via an enzyme-inhibitor approach represents a novel method in diagnostic nuclear medicine. Current problems in blood pool labelling could be overcome by using selective sulphonamide inhibitors as carriers. Red cell carbonic anhydrase is identified as an ideal target enzyme for such an approach. A brief review of the target enzyme is presented together with the screening of a series of synthesised sulphonamide inhibitors. p-Iodobenzenesulphonamide, 4-[(4-iodophenyl)thio]benzenesulphonamide and 5-(4-bromophenyl)sulphonyl]thiophene-2-sulphonamide were found to be particularly potent, reversible, lipophilic inhibitors of carbonic anhydrase, characteristics that warrant their further investigation as potential carriers. 4-Iodo-3-(iodoacetamido)benzenesulphonamide was a moderate inhibitor but caused relatively fast irreversible inactivation, making it a candidate for longer term studies.

The enzyme-inhibitor approach to cell-selective labelling—II. In vivo studies with pIBS in small animals and man

p-Iodobenzenesulphonamide (pIBS), a potent red cell carbonic anhydrase inhibitor, was used as a carrier for radioiodine in the enzyme-inhibitor approach to cell-specific blood labelling. Radioactivity distribution was monitored in rats and man following i.v. administration of the radiolabelled carrier or of pre-labelled red cells. Rat blood activity fitted a two compartment model; the half-life for overall elimination was 69 +/- 27 h. At 24 h most activity remained associated with red cells, but there was a significant uptake in the large intestine (10 +/- 6%). In man there was no significant accretion by gut or any other organ over 93 h, and the blood clearance was mono-exponential (t1/2 = 9.8 +/- 1.5 days).