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- Elmståhl, Barbara, et al.
(författare)
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Iodixanol 320 results in better renal tolerance and radiodensity than do gadolinium-based contrast media: Arteriography in ischemic porcine kidneys
- 2008
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Ingår i: Radiology. - : Radiological Society of North America (RSNA). - 1527-1315 .- 0033-8419. ; 247:1, s. 88-97
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To prospectively compare nephrotoxicity and radiodensity of plasma hyperosmotic gadolinium chelates (attenuation-osmotic ratio of 1: 1) with those of plasma iso-osmotic iodine-based contrast media (attenuation-osmotic ratio of 3: 1 or 6: 1) after renal arteriography in ischemic porcine kidneys. Materials and Methods: The local animal care committee approved this study. The following contrast media were used: (a) iodixanol (150 mg of iodine per milliliter and 320 mg I/mL, 0.29 osm/kg H2O), (b) iopromide (150 mg I/mL, 0.34 osm/kg), (c) 0.5 mol/L gadodiamide (0.78 osm/kg), and (d) 1.0 mol/L gadobutrol (1.6 osm/kg). After left-sided nephrectomy, contrast media (3 mL per kilogram of body weight) were injected (20 mL/min) in a noncrossover design into the right renal artery of pigs during a 10-minute ischemic period. There were eight pigs in each group and one group for each contrast medium. We compared histomorphology, radiographic contrast medium excretion, subjective radiodensity of nephrograms (70 kVp) at the end of injection, and contrast medium plasma half-life elimination times 1-3 hours after injection. Longer elimination times resulted in lower glomerular filtration rates. Results: Gadobutrol caused extensive tubular necrosis and moderate glomerular necrosis; gadodiamide and iopromide, minimal to mild tubular necrosis; and iodixanol, no necrosis. Gadobutrol was the only contrast medium to show no sign of excretion, and its plasma half-life elimination time (median, 1103 minutes; P = .001) was significantly longer than that of other contrast agents. Gadodiamide had a significantly longer plasma half-life elimination time (median, 209 minutes; P = .01) than did iodine-based contrast media (median, 136-142 minutes). The 320 mg I/mL dose of iodixanol had the highest radiodensity, whereas gadodiamide had the lowest radiodensity. The radiodensity of the 320 mg I/mL dose of iodixanol was greater than that of the 150 mg I/mL dose of iodixanol, which was equal to the radiodensities of the 150 mg I/mL dose of iopromide and 1.0 mol/L gadobutrol, which in turn were greater than that of 0.5 mol/L gadodiamide. Conclusion: Plasma iso-osmotic iodine-based contrast media used at commercially available concentrations have superior attenuation and nephrotoxic profiles compared with equal volumes of hyperosmotic nonionic 0.5-1.0 mol/L gadolinium-based contrast media when performing renal arteriographic procedures. (c) RSNA, 2008.
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| 2. |
- Orlova, Anna, et al.
(författare)
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Synthetic affibody molecules : a novel class of affinity ligands for molecular imaging of HER2-expressing malignant tumors
- 2007
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 67:5, s. 2178-2186
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Tidskriftsartikel (refereegranskat)abstract
- The Affibody molecule Z(HER2:342-pep2), site-specifically and homogeneously conjugated with a 1,4,7,10-tetra-azacylododecane-N,N',N'',N'''-tetraacetic acid (DOTA) chelator, was produced in a single chemical process by peptide synthesis. DOTA-Z(HER2:342-pep2) folds spontaneously and binds HER2 with 65 pmol/L affinity. Efficient radiolabeling with >95% incorporation of (111)In was achieved within 30 min at low (room temperature) and high temperatures (up to 90 degrees C). Tumor uptake of (111)In-DOTA-Z(HER2:342-pep2) was specific for HER2-positive xenografts. A high tumor uptake of 23% injected activity per gram tissue, a tumor-to-blood ratio of >7.5, and high-contrast gamma camera images were obtained already 1 h after injection. Pretreatment with Herceptin did not interfere with tumor targeting, whereas degradation of HER2 using the heat shock protein 90 inhibitor 17-allylamino-geldanamycin before administration of (111)In-DOTA-Z(HER2:342-pep2) obliterated the tumor image. The present results show that radiolabeled synthetic DOTA-Z(HER2:342-pep2) has the potential to become a clinically useful radiopharmaceutical for in vivo molecular imaging of HER2-expressing carcinomas.
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| 3. |
- Tolmachev, Vladimir, et al.
(författare)
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Radionuclide therapy of HER2-positive microxenografts using a 177Lu-labeled HER2-specific Affibody molecule
- 2007
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 67:6, s. 2773-2782
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Tidskriftsartikel (refereegranskat)abstract
- A radiolabeled anti-HER2 Affibody molecule (Z(HER2:342)) targets HER2-expressing xenografts with high selectivity and gives good imaging contrast. However, the small size (approximately 7 kDa) results in rapid glomerular filtration and high renal accumulation of radiometals, thus excluding targeted therapy. Here, we report that reversible binding to albumin efficiently reduces the renal excretion and uptake, enabling radiometal-based nuclide therapy. The dimeric Affibody molecule (Z(HER2:342))(2) was fused with an albumin-binding domain (ABD) conjugated with the isothiocyanate derivative of CHX-A''-DTPA and labeled with the low-energy beta-emitter (177)Lu. The obtained conjugate [CHX-A''-DTPA-ABD-(Z(HER2:342))(2)] had a dissociation constant of 18 pmol/L to HER2 and 8.2 and 31 nmol/L for human and murine albumin, respectively. The radiolabeled conjugate displayed specific binding to HER2-expressing cells and good cellular retention in vitro. In vivo, fusion with ABD enabled a 25-fold reduction of renal uptake in comparison with the nonfused dimer molecule (Z(HER2:342))(2). Furthermore, the biodistribution showed high and specific uptake of the conjugate in HER2-expressing tumors. Treatment of SKOV-3 microxenografts (high HER2 expression) with 17 or 22 MBq (177)Lu-CHX-A''-DTPA-ABD-(Z(HER2:342))(2) completely prevented formation of tumors, in contrast to mice given PBS or 22 MBq of a radiolabeled non-HER2-binding Affibody molecule. In LS174T xenografts (low HER2 expression), this treatment resulted in a small but significant increase of the survival time. Thus, fusion with ABD improved the in vivo biodistribution, and the results highlight (177)Lu-CHX-A''-DTPA-ABD-(Z(HER2:342))(2) as a candidate for treatment of disseminated tumors with a high level of HER2 expression.
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