In vitro comparison of renal handling and uptake of two somatostatin receptor-specific peptides labeled with indium-111

Trejtnar, František; Nový, Zbyněk; Petřík, Miloš; Lázníčková, Alice; Melicharova, Ludmila; Vaňková, Marie; Lázníček, Milan

doi:10.1007/s12149-008-0192-6

Cited by 12 publications

(16 citation statements)

References 31 publications

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“…Several ligands have been reported to bind both to megalin and to cubilin (8). In vitro studies have indicated that radiolabeled somatostatin analogs are actively reabsorbed in proximal tubular cells by receptor-mediated endocytosis, probably involving megalin or cubilin (11). Autoradiography studies of rodent kidneys showed that various radiolabeled peptides accumulate mainly in the renal cortex (12).…”

Section: Proximal Tubular Reabsorption and Processingmentioning

confidence: 99%

Renal Toxicity of Radiolabeled Peptides and Antibody Fragments: Mechanisms, Impact on Radionuclide Therapy, and Strategies for Prevention

Vegt¹,

Jong²,

Wetzels³

et al. 2010

J Nucl Med

257

251

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Peptide-receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs such as octreotide is an effective therapy against neuroendocrine tumors. Other radiolabeled peptides and antibody fragments are under investigation. Most of these compounds are cleared through the kidneys and reabsorbed and partially retained in the proximal tubules, causing dose-limiting nephrotoxicity. An overview of renal handling of radiolabeled peptides and resulting nephrotoxicity is presented, and strategies to reduce nephrotoxicity are discussed. Modification of size, charge, or structure of radiolabeled peptides can alter glomerular filtration and tubular reabsorption. Coinfusion of competitive inhibitors of reabsorption also interferes with the interaction of peptides with renal endocytic receptors; coinfusion of basic amino acids is currently used for kidney protection in clinical PRRT. Furthermore, nephrotoxicity may be reduced by dose fractionation, use of radioprotectors, or use of mitigating agents. Decreasing the risk of nephrotoxicity allows for administration of higher radiation doses, increasing the effectiveness of PRRT.

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Section: Proximal Tubular Reabsorption and Processingmentioning

confidence: 99%

Renal Toxicity of Radiolabeled Peptides and Antibody Fragments: Mechanisms, Impact on Radionuclide Therapy, and Strategies for Prevention

Vegt¹,

Jong²,

Wetzels³

et al. 2010

J Nucl Med

257

251

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“…Ligands with carboxyl groups on dangling chains are normally evaluated in renal tracer development because the interaction of the renal receptor with the carboxyl group is important for clearance of small peptides 14-16. Tridentate ligands being investigated in bioconjugates or in tracers often have the dangling group attached to a central N anchoring the two chelate rings 10,17-19.…”

Section: Introductionmentioning

confidence: 99%

NH NMR Shifts of New Structurally Characterized fac-[Re(CO)₃(polyamine)]ⁿ⁺ Complexes Probed via Outer-Sphere Hydrogen-Bonding Interactions to Anions, Including the Paramagnetic [Re^IVBr₆]²⁻ Anion

et al. 2010

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fac-[Re I (CO) 3 L] n complexes serve as models for short-lived fac-[ 99m Tc I (CO) 3 L] imaging tracers (L = tridentate ligands forming two five-membered chelate rings defining the L face). Dangling groups on L, needed to achieve desirable biodistribution, complicate the NMR spectra, which are not readily understood. Using less complicated L, we found that NH groups (exo-NH) projecting toward the L face sometimes showed an upfield shift attributable to steric shielding of the exo-NH group from the solvent by the chelate rings. Our goal is to advance our ability to relate these spectral features to structure and to solution properties. To investigate whether exo-NH groups in six-membered rings exhibit the same effect and whether the presence of dangling groups alters the effect, we prepared new fac-[Re(CO) 3 L] n complexes that allow direct comparisons of exo-NH shifts for six-membered vs. five-membered chelate rings. New complexes were structurally characterized with the following L: dipn (N-3-(aminopropyl)-1,3-propanediamine); N'-Medipn (3,3′-diamino-Nmethyldipropylamine); N,N-Me 2 dipn (N,N-dimethyldipropylenetriamine); aepn (N-2-(aminoethyl)-1,3-propanediamine); trpn (tris-(3-aminopropyl)amine); and tren (tris-(2-aminoethyl)amine). In DMSO-d 6 , the upfield exo-NH signals were exhibited by all complexes, indicating that the rings sterically shield the exo-NH groups from bulky solvent molecules. This interpretation was supported by exo-NH signal shift changes caused by added halide and [ReBr 6 ] 2− anions, consistent with outer-sphere H-bond interactions between these anions and the exo-NH groups. For fac- [Re(CO) 3 (dipn)]PF 6 in acetonitrile-d 3 , the exo-NH signal shifted further downfield in the series, Cl − > Br − > I − , and the plateau in shift change required lower concentration for smaller anions. These results are consistent with steric shielding of the exo-NH groups by the chelate rings. Nevertheless, despite its size, the shape and the charge of [ReBr 6 ] 2− allowed the dianion to induce large upfield paramagnetic shifts of the exo-NH signal of fac-[Re(CO) 3 (dipn)]PF 6 . This dianion shows promise as an outer-sphere H-bonding paramagnetic shift reagent. 21 For both isomers in the solid state, the coordinated carboxyl group is deprotonated, whereas the dangling carboxyl group is protonated. Two types of terminal NH's were defined and unambiguously identified through the crystallography of the two isomers. In one isomer, the terminal amine has an endo-NH proton (defined as the proton projecting toward the carbonyl ligands, Figure 1) with a normal relatively downfield shift (5.84 ppm, DMSO-d 6 ) for a terminal secondary amine NH signal. In the other isomer, this amine has an exo-NH proton (defined as the proton projecting away from the carbonyl ligands, Figure 1). 21 The signal of this terminal secondary amine exo-NH proton was observed at a rather upfield position (5.36 ppm, DMSO-d 6 ). NIH Public AccessIn later studies, 24 We hypothesized that the shift differences might be attributable in ...

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“…The time of the renal half-excretion of protein correlates with the molecular size: the limit of glomerular filtration is estimated at 60-65 kDa [15]. The full-size IgG molecules (~150 kDa) (Fig.…”

Section: Truncated Antibody Fragments and Alternative Framework Prmentioning

confidence: 97%

Modern Technologies for Creating Synthetic Antibodies for Clinical Application

Deyev

Лебеденко

2009

Acta Naturae

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The modular structure and versatility of antibodies enables one to modify natural immunoglobulins in different ways for various clinical applications. Rational design and molecular engineering make it possible to directionally modify the molecular size, affinity, specificity, and immunogenicity and effector functions of an antibody, as well as to combine them with other functional agents. This review focuses on up-to-date methods of antibody engineering for diagnosing and treating various diseases, particularly on new technologies meant to refine the effector functions of therapeutic antibodies.

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In vitro comparison of renal handling and uptake of two somatostatin receptor-specific peptides labeled with indium-111

Cited by 12 publications

References 31 publications

Renal Toxicity of Radiolabeled Peptides and Antibody Fragments: Mechanisms, Impact on Radionuclide Therapy, and Strategies for Prevention

Renal Toxicity of Radiolabeled Peptides and Antibody Fragments: Mechanisms, Impact on Radionuclide Therapy, and Strategies for Prevention

NH NMR Shifts of New Structurally Characterized fac-[Re(CO)₃(polyamine)]ⁿ⁺ Complexes Probed via Outer-Sphere Hydrogen-Bonding Interactions to Anions, Including the Paramagnetic [Re^IVBr₆]²⁻ Anion

Modern Technologies for Creating Synthetic Antibodies for Clinical Application

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In vitro comparison of renal handling and uptake of two somatostatin receptor-specific peptides labeled with indium-111

Cited by 12 publications

References 31 publications

Renal Toxicity of Radiolabeled Peptides and Antibody Fragments: Mechanisms, Impact on Radionuclide Therapy, and Strategies for Prevention

Renal Toxicity of Radiolabeled Peptides and Antibody Fragments: Mechanisms, Impact on Radionuclide Therapy, and Strategies for Prevention

NH NMR Shifts of New Structurally Characterized fac-[Re(CO)3(polyamine)]n+ Complexes Probed via Outer-Sphere Hydrogen-Bonding Interactions to Anions, Including the Paramagnetic [ReIVBr6]2− Anion

Modern Technologies for Creating Synthetic Antibodies for Clinical Application

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NH NMR Shifts of New Structurally Characterized fac-[Re(CO)₃(polyamine)]ⁿ⁺ Complexes Probed via Outer-Sphere Hydrogen-Bonding Interactions to Anions, Including the Paramagnetic [Re^IVBr₆]²⁻ Anion