NUCLEAR SCIENCE SERIES NAS-NS Nuclear Medicine THE CHEMISTRY OF TECHNETIUM IN MEDICINE

Transcription

1 oc f * * t NUCLEAR SCIENCE SERIES NAS-NS-3204 Nuclear Medicine THE CHEMISTRY OF TECHNETIUM IN MEDICINE by Joseph Steigman Department of Radiology Division of Nuclear Medicine Downstate Medical Center, Brooklyn, New York and William C. Eckelman The Bristol-Myers Squibb Pharmaceutical Research Institute Princeton, New Jersey Prepared for the Committee on Nuclear and Radiochemistry Board on Chemical Sciences and Technology Commission on Physical Sciences, Mathematics, and Applications National Research Council National Academy Press Washington, D.C. 1992

2 CONTENTS Introduction 1 Methods of Analysis of Technetium-99 3 Sources of Technetium-99m 5 A. The Brookhaven Generator 6 B. Instant Technetium 8 C. Sublimation Generator 9 IV. Technetium (VII) Compounds 10 A. General Chemistry of Tc (VII) 10 B. Pertechnetate Binding To Proteins 10 C. Technetium Sulfur Colloid - (Co-authored by Karen Linder) 11 D. The Reduction Potential of Technetium (VII) 14 V. The Chemistry of Various Reducing Agents Used with Pertechnetate 16 A. SnCl 2 «2H 2 O 16 B. Sodium Borohydride 18 C. Sodium Dithionite 19 D. Hypophosphorous Acid 20 E. Hydrazine 20 F. Ascorbic Acid 21 G. Sulfhydryl (and related) Compounds 22 H. Sulfur Dioxide 23 I. Hydrochloric Acid 23 J. Formamidine Sulfinic Acid 24 VII

3 K. Hydroxylamine 24 L. Solid or Second-Phase Reductants 25 M. Tertiary Organic Phosphines and Arsines 26 N. Nature of the Reduced Technetium Complexes 27 VI. Technetium (VI) Compounds 29 A. Tc(VI) Oxygen Compounds 29 B. Tc(VI) Sulfur Compounds 30 C. Tc(VI) Nitrido Compounds 32 VII. Technetium(V) Compounds 33 A. Sulfhydryl Compounds Synthesis and Structure of Monodentate Sulfur-Based Compounds Mechanism of Reduction of Pertechnetate by Cysteine Crystal Structure Determination 36 B. Synthesis and Structures of Bidentate Sulfur-Based Complexes Introduction Mixed Sulfur-Oxygen and Sulfur-Nitrogen Compounds Conclusion 39 C. Tc(V) Complexes with Oxygen Compounds Introduction Polyhydric Alcohols Polyhydric Acids Tc-Glucoheptonate 42 D. Compounds of Tc(V) and Nitrogen-Containing Ligands 43 E. Mixed Nitrogen-Oxygen Complexes of Tc(V) 46 F. Nitrido Complexes of Technetium(V) 49 G. Some Additional Compounds of Technetium(V) Thiocyanate Complex Cyanide Complexes Arsine Complexes EDTA Complex A New Type of Tc(V) Core 51 H. Displacement Reactions and Mixed-Ligand Complexes of Tc(V) 52 I. Binding of Tc(V) Compounds to Plasma 53 VIII. Technetium (IV) Compounds 55 A. Halide Complexes and Oxide of Tc (IV) 55 VIII

4 1. Halide Complexes 55 a. Preparation 55 b. Physical - Chemical Properties Oxide of Tc 57 a. Preparation 57 b. Physical - Chemical Properties 57 c. Solubility of TcO 2 «xh 2 O 58 B. Polyhydroxy and Hydroxy-Acid Complexes of Tc (IV) Ethylene Glycol Citrate Carboxylic Acids 61 C. Amino-Carboxylate Complexes of Tc (IV) 61 D. Thiol Complexes of Tc (IV) Cysteine Penicillamine Dimercaptosuccinate (DMSA) 66 E. Thiosemicarbazone Complex of Tc (IV) 67 F. Complexes with Phosphorus (V) Ligands Inorganic Phosphorus Compounds 67 a. Phosphate Complexes 67 b. Pyrophosphate Complexes 67 c. Tripolyphosphate Complex Organic Phosphorus Compounds 69 a. Methylene Diphosphonate 69 b. Hydroxyethylidene Diphosphonate Oxidation State of Technetium Number and Nature of Tc (EHDP) Complexes Theory of Determining Charge to Mass Ratio Theory of Gel Chromatography Separation by Molecular Weight on Gel Chromatography Separation by Ion Exchange Separation by Charge on Ion Exchange Chromatography Separation by Molecular Weight on Ion Exchange Chromatography Activity Coefficients for Ion Exchange Chromatography 76

5 10. Theoretical Considerations 78 G. Tc(IV) Phosphines and Related Complexes 78 H. Other Complexes of Tc(IV) 79 IX. Technetium (III) Compounds 81 A. Halogen Compounds 81 B. Thiourea Complexes 81 C. Aminocarboxylate Complexes 82 D. Acetylacetone (acac) Complexes 83 E. Phosphine and Arsine Complexes Phosphine-Halogen and Arsine-Halogen Complexes Phosphine-Schiff Base Complexes Mixed Phosphine - Thio Complexes Mixed Phosphine - Carbon Monoxide Complexes Mixed Hydrido - Phosphine Complexes 87 F. Cyanide Complexes 87 G. Thiocyanate Complexes 88 H. Oxime Complexes of Technetium (III) 88 X. Technetium (II) Compounds 91 A. Chloro Complexes and Related Compounds 91 B. Phosphine and Arsine Complexes 91 C. Nitrosyl Complexes 92 XI. Technetium (I) Complexes 93 A. Nitrosyl Complexes 93 B. Organometallic Complexes 93 C. Carbonyl Complexes 94 D. Hexacyano Complexes 95 E. Isonitriles 95 F. Other complexes of Tc (I) and Tc (II) 96 XII. Complexes of Tc(O) 97 A. Ditechnetium Decacarbonyl Complexes 97 B. Technetium Dinitrogen Complexes 97 XIII. Tc-99m Radiopharmaceutical Preparations 98 A. General Considerations 98 B. Methods of Chemical Characterization of 99m Tc Complexes Polarography and Coulometry Chromatography Ion-exchange Chromatography 103

6 4. Solvent Extraction Electrophoresis 105 C. Labeling Proteins with 99m Tc 106 D. After-thoughts on Disulfide Reduction by Sn(II) 108 E. Recent Advances 109 XIV. Structure and Stereochemistry in Technetium Coordination Complexes (Chapter contributed by D.P. Nowotnik and S.S. Jurisson) 111 A. Introduction 111 B. The Structure of Technetium Complexes 112 C. Stereochemistry in Technetium Complexes Organic Stereochemistry Nomenclature Inorganic Stereochemistry Nomenclature Constitutional Isomers Positional Isomers Stereochemistry in Tc (V) O Complexes Stereochemistry in Octahedral Technetium Complexes 127 BIBLIOGRAPHY 131 U~ xi