Targeting radiopharmaceuticals--II. Evaluation of new trivalent metal complexes with different overall charges. 1991

Y Sun, and C J Mathias, and M J Welch, and S L Madsen, and A E Martell
Edward Mallinckrodt Institute of Radiology, Washington University Medical School, St Louis, MO 63110.

Three new multidentate ligands designed to have high affinity for Ga3+, In3+ and Fe3+ have been synthesized. N-(2-hydroxybenzyl)-N'-pyridoxylethylenediamine-N,N'-diacetic acid (HBPLED), N-(2-hydroxy-3,5-dimethylbenzyl)-N'-(3-hydroxy-1,2,5-trimethyl-4- pyridylmethyl)ethylenediamine-N,N'-diacetic acid (Me4HBPLED) and N,N'-bis(3-hydroxy-1,2,5-trimethyl-4-pyridylmethyl) ethylenediamine-N,N'-diacetic acid (DMPLED). These ligands give metal-ligand (M-L) complexes with (M = Ga3+, In3+, Fe3+) overall charges of -1.0 and +1, respectively. The 67Ga, 68Ga and 111In complexes of each of the three ligands and the 59Fe complex of Me4HBPLED were prepared, characterized and their biodistributions determined in rats after intravenous injection. Despite the differences in overall charge, the biological behavior of all three 111In complexes were similar, in that the radioactivity cleared rapidly via the kidney. The biodistributions of the 68Ga and 67Ga complexes were comparable to that of the 111In complex counterpart. Also, the 59Fe-Me4HBPLED biodistribution was not significantly different from those of the 68Ga- and 111In-Me4HBPLED. The renal clearance rate seems insensitive to the overall M-L charge; suggesting that the hydrophilic periphery of the ligand rather than the overall molecular charge determines the biological fate (with respect to renal clearance).

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
D007504 Iron Radioisotopes Unstable isotopes of iron that decay or disintegrate emitting radiation. Fe atoms with atomic weights 52, 53, 55, and 59-61 are radioactive iron isotopes. Radioisotopes, Iron
D008024 Ligands A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed) Ligand
D008670 Metals Electropositive chemical elements characterized by ductility, malleability, luster, and conductance of heat and electricity. They can replace the hydrogen of an acid and form bases with hydroxyl radicals. (Grant & Hackh's Chemical Dictionary, 5th ed) Metal
D009682 Magnetic Resonance Spectroscopy Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING). In Vivo NMR Spectroscopy,MR Spectroscopy,Magnetic Resonance,NMR Spectroscopy,NMR Spectroscopy, In Vivo,Nuclear Magnetic Resonance,Spectroscopy, Magnetic Resonance,Spectroscopy, NMR,Spectroscopy, Nuclear Magnetic Resonance,Magnetic Resonance Spectroscopies,Magnetic Resonance, Nuclear,NMR Spectroscopies,Resonance Spectroscopy, Magnetic,Resonance, Magnetic,Resonance, Nuclear Magnetic,Spectroscopies, NMR,Spectroscopy, MR
D011919 Rats, 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. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D005260 Female Females
D005710 Gallium Radioisotopes Unstable isotopes of gallium that decay or disintegrate emitting radiation. Ga atoms with atomic weights 63-68, 70 and 72-76 are radioactive gallium isotopes. Radioisotopes, Gallium
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
D014018 Tissue Distribution Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. Distribution, Tissue,Distributions, Tissue,Tissue Distributions

Related Publications

Y Sun, and C J Mathias, and M J Welch, and S L Madsen, and A E Martell
February 1995, The Journal of rheumatology. Supplement,
Y Sun, and C J Mathias, and M J Welch, and S L Madsen, and A E Martell
March 2009, Chemical communications (Cambridge, England),
Y Sun, and C J Mathias, and M J Welch, and S L Madsen, and A E Martell
October 2012, Molecular cancer therapeutics,
Y Sun, and C J Mathias, and M J Welch, and S L Madsen, and A E Martell
December 2014, Inorganic chemistry,
Y Sun, and C J Mathias, and M J Welch, and S L Madsen, and A E Martell
May 1994, Die Pharmazie,
Y Sun, and C J Mathias, and M J Welch, and S L Madsen, and A E Martell
February 2013, Journal of the American Society for Mass Spectrometry,
Y Sun, and C J Mathias, and M J Welch, and S L Madsen, and A E Martell
December 2006, Inorganic chemistry,
Y Sun, and C J Mathias, and M J Welch, and S L Madsen, and A E Martell
January 2002, Biofizika,
Y Sun, and C J Mathias, and M J Welch, and S L Madsen, and A E Martell
March 2023, Chemistry (Weinheim an der Bergstrasse, Germany),
Y Sun, and C J Mathias, and M J Welch, and S L Madsen, and A E Martell
October 2022, Dalton transactions (Cambridge, England : 2003),
Copied contents to your clipboard!