Sandra J. Gribben
University of Nottingham
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Featured researches published by Sandra J. Gribben.
European Journal of Nuclear Medicine and Molecular Imaging | 1994
M. V. Pimm; Sandra J. Gribben
Systemic administration of lysine to mice injected with indium-111-labelled Fab fragment of a monoclonal antibody has been shown to reduce renal uptake/retention of the radiometal. This treatment should be applicable to clinical immunoscintigraphy and radioimmunotherapy with radiometal-labelled antibody fragments.
Journal of Controlled Release | 1995
M. V. Pimm; Sandra J. Gribben; Katalin Bogdán; Ferenc Hudecz
Abstract The biodistribution has been assessed in mice of synthetic branched polypeptides. These were: A poly( l -lysine) backbone with short side chains of three dl -alanine residues (AK, which is polycationic); AK with an additional glutamic acid residue at the end of the branches (EAK, which is amphoteric); EAK whose terminal glutamic acid amino groups had been acetylated (Ac-EAK, which is polyanionic) or succinylated (Suc-EAK, which is highly polyanionic). Each was labelled with gamma emitting radionuclides suitable for use in biodistribution studies (125I and 51Cr) or for gamma scintigraphy (111In). Regardless of the radiolabel, both EAK and Ac-EAK showed prolonged survival in the blood over a four hour observation period, while polycationic AK or highly polyanionic Suc-EAK were rapidly cleared. There were great differences in organ retention of the different radionuclides from any one polypeptide. With AK there were much higher levels of 51Cr than of 111In or 125I in spleen, liver and lung. With EAK, there were higher levels of 51Cr than of 111In or 125I in liver and spleen, but higher levels of 111In than of 51Cr or 125I in kidney. The pattern was similar with Ac-EAK, but the high kidney level of 111In seen with EAK was not present. With Suc-EAK, biodistribution of 111In and 51Cr were virtually identical with very high levels in spleen and liver, which were not seen with 125I. This study has shown that only amphoteric or mildly anionic polypeptides survive well in the circulation. Cationic or highly anionic polypeptides survive poorly, but have different sites of clearance, the former going particularly to spleen, kidney, liver and lung, the latter particularly to spleen and liver. However the apparent site of clearance depends upon the labelling radionuclide. Presumably, this reflects the handling within organs of the particular radioelement and/or (in the case of radiometals) the amino acids to which its chelating DTPA was covalently linked.
European Journal of Nuclear Medicine and Molecular Imaging | 1991
M. V. Pimm; Ranbir S. Rajput; M. Frier; Sandra J. Gribben
A reduction-mediated technetium-99m labelling method has been evaluated with a range of tumour-specific monoclonal antibodies. Antibodies reduced with 2-mercaptoethanol (2-ME) had free sulphydryl groups, but their number was much higher than could be accounted for by only limited intra-chain reduction of disulphide bonds. Reduced antibody could be labelled efficiently with 99mTc using an methylene diphosphonate (MDP) bone-scanning kit, although this seemed to depend on the presence of residual 2-ME in the preparations. With a carcinoembryonic antigen (CEA)-specific antibody, immunoreactivity of labelled antibody was confirmed, and after injection into nude with CEA-producing xenografts there was localisation into the tumours. Sephacryl S300 gel filtration showed the radiolabel eluting at a single discrete peak at the expected 150 kDa. However, examination of all of the labelled antibodies by polyacrylamide gel electrophoresis (PAGE) and autoradiography showed the presence of a large number of radiolabelled low molecular weight degradation products of the antibodies. These degradation products seemed to be formed in previously reduced antibodies during processing for PAGE, indicating some fragility of the reduced antibody.
Annals of Nuclear Medicine | 1995
M. V. Pimm; Alan C. Perkins; Sandra J. Gribben; D. Gaál; Ferenc Hudecz
Radiolabelled synthetic branched chain polypeptides (BCP) represent a new and novel range of materials with potential as radiopharmaceuticals. Preliminary imaging studies have been under-taken with111In-labelled BCP in mice with subcutaneously transplanted mammary carcinoma. Four polypeptides each with a poly(L-lysine) backbone and side chains of DL-alanine residues were studied. These were AK, which is polycationic, EAK which is amphoteric, having additional glutamic acid residues at the end of the side chains, and AcEAK (anionic) and SucEAK (highly polyanionic) where the terminal glutamic acid amino groups were acetylated or succinylated respectively. Radiolabelling was achieved by previous conjugation with DTPA. Serial images up to 48 hours showed marked retention of111In-labelled polycationic AK and polyanionic SucEAK in the liver and spleen, with renal uptake also being visible in the case of AK.111In-labelled EAK and AcEAK showed longer blood survival with some liver uptake, but tumour uptake was also visualized by 24 hours with both of these polypeptides. These studies demonstrate the feasibility of using111In-labelled synthetic branched chain polypeptides as radiopharmaceuticals for gamma scintigraphy and the visualization of tumours by modification of the side chain structure. These materials warrant further study.
European Journal of Nuclear Medicine and Molecular Imaging | 1992
M. V. Pimm; Sandra J. Gribben
Three tumour-specific monoclonal antibodies (MoAbs) showed localisation in human tumour xenografts in nude mice, although the tumour discrimination was limited by the survival of a greater proportion of the MoAb in the blood and body as a whole. An attempt was made to increase tumour discrimination by the subsequent administration of syngeneic idiotypic-specific MoAbs (anti-id) directed against the first antibodies, in the expectation of clearing excess of the first MoAb from the circulation. With one MoAb (NCRC-2), its anti-id (NCRC-60) did effectively clear it from the blood, and, at least within a few hours, the tumour-to-blood ratios were increased. After longer periods, however, the tumour levels of NCRC-2 were also reduced, and the tumour discrimination was no longer increased. With another MoAb (NCRC-23) the tumour levels were reduced to a greater extent than were the blood levels in mice treated with its anti-id (NCRC-59), so that rather than being increased the tumour discrimination was actually reduced to about a third of that in control mice. With a third MoAb (NCRC-48), there was no effect on the tumour or blood levels within a few hours of injection of its anti-id (NCRC-62), and so there was no short-term effect on tumour discrimination. Subsequently, however, the tumour levels were slightly reduced, while the blood levels increased in mice treated with anti-id compared with control mice, so that the tumour-to-blood ratios decreased. These studies have shown a variety of effects of syngeneic anti-id MoAbs on tumour discrimination by their target MoAbs, and overall the indication is that such anti-ids selected indiscriminately are likely to be of little value for enhancing target recognition by murine or human MoAbs given for diagnostic or therapeutic purposes.
Nuclear Medicine and Biology | 1994
M. V. Pimm; Sandra J. Gribben
Abstract The effect of systemic treatment with DTPA on the whole body retention and biodistribution of 111 In from labelled albumin, γ-globulin and a synthetic polylysine has been examined in mice. Although treatment greatly accelerated clearance of free 111 In, it had much less effect on the biodistribution of the tracer from labelled materials, over and above what was probably due to free 111 In in the preparations. This suggests that systemic treatment with DTPA is unlikely to have a major impact on target discrimination during scintigraphy with 111 In labelled radio-pharmaceuticals, such as monoclonal antibodies.
European Journal of Nuclear Medicine and Molecular Imaging | 1990
M. V. Pimm; Alan C. Perkins; Sandra J. Gribben; Amanda J. Markham
As a model for human mouse-specific antibody responses in patients undergoing immunoscintigraphy, we have investigated in rats the production of mouse-specific antibodies (MA) to the mouse monoclonal antibody 791T/36. At intervals of between 5 and 16 weeks the rats were given repeated cycles of intravenous (IV) injections of antibody with or without a simultaneous intradermal (ID) injection. The IV dose was 60 gmg/kg, a dose similar to that used in many clinical immunoscintigraphy studies. The ID injection was 2 μg, which mimicks the skin test dose often given in clinical imaging protocols. The study was carried out with both131I-labelled antibody and with antibody labelled with111In by diethylenetriamine-penta-acetic acid (DTPA) chelation. MA was measured with a passive haemagglutination assay using sheep red blood cells coated with the monoclonal antibody. Of rats given ID injections of unlabelled antibody at the same time as the IV imaging doses, 9/20 produced MA during 4 cycles of injections. In contrast, only 2/16 rats given only the IV dose produced MA. Both131I- and111In-labelled antibody appeared equally immunogenic with 5/18 and 6/18 overall responders, respectively. The production of MA was associated with a significant perturbation in the biodistribution of the IV dose of labelled antibody as seen by gamma-camera imaging of the rats given111In-labelled antibody. There was clearance of immune complexes to the liver, this organ accumulating up to 90% of the whole body count rate of radiolabel. MA titres of between 1/100 and 1/78000 caused equal perturbation of biodistribution, although below 1/100 the effect was more variable.
Journal of Labelled Compounds and Radiopharmaceuticals | 1995
M. V. Pimm; Sandra J. Gribben; Ferenc Hudecz
Nuclear Medicine and Biology | 1994
M. V. Pimm; Sandra J. Gribben
Journal of nuclear biology and medicine | 1994
M. V. Pimm; Alan C. Perkins; Sandra J. Gribben; Ferenc Hudecz