Influence of endogenous biotin on the biodistribution of labelled biotin derivatives in mice. 1995

M Rusckowski, and M Fogarasi, and F Virzi, and D J Hnatowich
Department of Nuclear Medicine, University of Massachusetts Medical Center, Worcester 01655, USA.

Previously, this laboratory reported that in mice pre-targeted with unlabelled streptavidin, the biodistribution of 111In administered on one biotin derivative (EB1) was superior to that of another derivative (DB2). In addition, a Scatchard analysis showed that the affinity constant of 111In-EB1 is lower by seven orders of magnitude from that of 111In-DB2. Therefore, this paper considers the role that endogenous biotin may play in these observations. Both 111In-labelled EB1 and DB2 were bound to streptavidin and incubated at 37 degrees C in mouse blood with increasing concentrations of d-biotin. As determined by Sephadex G-50 chromatography, only an 8-fold molar excess of d-biotin relative to labelled streptavidin was required to displace 90% of label in the case of EB1, whereas even a 20-fold molar excess provided no detectable displacement of DB2. That this displacement was also occurring in vivo was established in a mouse model bearing an infected thigh: increasing the serum biotin level (by intraperitoneal administration of d-biotin) had no effect on the biodistribution of 111In when administered on DB2; however, the target to non-target ratio decreased in the case of EB1. We have also observed that the biodistribution is no longer favourable when EB1 is administered radiolabelled with 99Tcm. When 111In was substituted with 99Tcm on EB1, chromatography of blood samples showed that similar displacement was occurring; however, in this case, the displaced label bound to serum proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D007205 Indium Radioisotopes Unstable isotopes of indium that decay or disintegrate emitting radiation. In atoms with atomic weights 106-112, 113m, 114, and 116-124 are radioactive indium isotopes. Radioisotopes, Indium
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D012016 Reference Values The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality. Normal Range,Normal Values,Reference Ranges,Normal Ranges,Normal Value,Range, Normal,Range, Reference,Ranges, Normal,Ranges, Reference,Reference Range,Reference Value,Value, Normal,Value, Reference,Values, Normal,Values, Reference
D004369 Pentetic Acid An iron chelating agent with properties like EDETIC ACID. DTPA has also been used as a chelator for other metals, such as plutonium. DTPA,Diethylenetriamine Pentaacetic Acid,Pentetates,Penthanil,Ca-DTPA,CaDTPA,CaNa-DTPA,Calcium Trisodium Pentetate,DETAPAC,Indium-DTPA,Mn-Dtpa,Pentacin,Pentacine,Pentaind,Pentetate Calcium Trisodium,Pentetate Zinc Trisodium,Sn-DTPA,Zinc-DTPA,Indium DTPA,Pentaacetic Acid, Diethylenetriamine,Pentetate, Calcium Trisodium,Zinc DTPA
D004492 Edetic Acid A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive. EDTA,Edathamil,Edetates,Ethylenediaminetetraacetic Acid,Tetracemate,Calcium Disodium Edetate,Calcium Disodium Versenate,Calcium Tetacine,Chelaton 3,Chromium EDTA,Copper EDTA,Coprin,Dicobalt EDTA,Disodium Calcitetracemate,Disodium EDTA,Disodium Ethylene Dinitrilotetraacetate,Distannous EDTA,Edetate Disodium Calcium,Edetic Acid, Calcium Salt,Edetic Acid, Calcium, Sodium Salt,Edetic Acid, Chromium Salt,Edetic Acid, Dipotassium Salt,Edetic Acid, Disodium Salt,Edetic Acid, Disodium Salt, Dihydrate,Edetic Acid, Disodium, Magnesium Salt,Edetic Acid, Disodium, Monopotassium Salt,Edetic Acid, Magnesium Salt,Edetic Acid, Monopotassium Salt,Edetic Acid, Monosodium Salt,Edetic Acid, Potassium Salt,Edetic Acid, Sodium Salt,Ethylene Dinitrilotetraacetate,Ethylenedinitrilotetraacetic Acid,Gallium EDTA,Magnesium Disodium EDTA,N,N'-1,2-Ethanediylbis(N-(carboxymethyl)glycine),Potassium EDTA,Stannous EDTA,Versenate,Versene,Acid, Edetic,Acid, Ethylenediaminetetraacetic,Acid, Ethylenedinitrilotetraacetic,Calcitetracemate, Disodium,Dinitrilotetraacetate, Disodium Ethylene,Dinitrilotetraacetate, Ethylene,Disodium Versenate, Calcium,EDTA, Chromium,EDTA, Copper,EDTA, Dicobalt,EDTA, Disodium,EDTA, Distannous,EDTA, Gallium,EDTA, Magnesium Disodium,EDTA, Potassium,EDTA, Stannous,Edetate, Calcium Disodium,Ethylene Dinitrilotetraacetate, Disodium,Tetacine, Calcium,Versenate, Calcium Disodium
D004927 Escherichia coli Infections Infections with bacteria of the species ESCHERICHIA COLI. E coli Infections,E. coli Infection,Infections, E coli,Infections, Escherichia coli,E coli Infection,E. coli Infections,Escherichia coli Infection,Infection, E coli,Infection, E. coli,Infection, Escherichia coli
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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