Contribution of electrospray mass spectrometry for the characterization, design, and development of nitrido technetium and rhenium heterocomplexes as potential radiopharmaceuticals

  I. Introduction 00A.  A Bit of History of Element 43 00B.  Group 7 Metals Relevant to NM: Technetium and Rhenium 00C.  “Essential” and “Receptor‐Specific” Technetium Radiopharmaceuticals 00D.  Therapeutic Rhenium Radiopharmaceuticals 00  II. Asymmetric Nitrido‐T c and ‐R e Heterocomplexes 00A.  Chemistry Underlying the Synthesis of Nitrido Heterocomplexes 00B.  Mono‐Cationic [Tc(N)(DTC)(PNP)] + Compounds for Heart Imaging 00C.  Contribution of ESI‐MS for the Characterization of Nitrido Technetium and Rhenium Heterocomplexes 00    1.  ESI‐MS Characterization of “Cold” Rhenium Compounds 00    2.  ESI‐MS Characterization of Radioactive 99g Tc Compounds 00    3.  MS‐MS of Isostructural 99g Tc and Re Compounds 00    4.  ESI‐MS of Receptor‐Specific 99g Tc Radiopharmaceuticals 00   III. Conclusions 00 Abbreviations 00 Acknowledgments 00 References 00Diagnostic nuclear medicine (NM) is among the imaging procedures (together with X‐ray, computerized tomography, magnetic resonance, and echography) the clinicians can routinely adopt to image organs or tissues and related disorders. 99m Tc‐based agents are the radiopharmaceuticals of election in diagnostic NM because of the ideal physical properties of the 99m Tc nuclide (t 1/2 6.01 hr; E γ 142 keV), low cost, and easy availability through the commercial 99 Mo/ 99m Tc generator, and chemical versatility of the element. In the last two decades the synergistic work of clinics, pharmacologists, and coordination chemists has had a tremendous impact in the development of new 99m Tc‐based radiopharmaceuticals through the recognition of the structure at the molecular level of the agent utilized. This has been achieved by studying the physico‐chemical properties of the long‐lived 99g Tc (t 1/2 2.11 × 10 5 year; E β 292 keV) and third‐row congener Re isostructural compounds. Electrospray ionization mass spectrometry (ESI‐MS) and collision experiments (MS/MS) represent valuable analytical techniques suitable for the characterization of both technetium and rhenium complexes relevant to NM. Unequivocal structural identification of these bioinorganic compounds, either simple coordination complexes (“essential radiopharmaceuticals”) or more sophisticated structures carrying bioactive fragments (“receptor‐specific” radiopharmaceuticals), can be realized in combination with multinuclear NMR spectroscopy. MS/MS experiments provide useful information on the different metal‐ligand bond strength, and comparison of the fragmentation profiles of isostructural technetium and rhenium compounds give additional details on the role played by the metal in determining preferred decomposition channels. The analysis of these data contribute to design novel synthetic strategies for the obtainment of technetium and rhenium compounds relevant to NM. The chemistry underlying the production of a new class of potential radiopharmaceuticals including a terminal nitrogen bond and a mixed coordination sphere comprising heterodiphosphines and/or dithiocarbamates (DTC) is presented in detail together with the ESI‐MS and MS/MS investigations. © 2004 Wiley Periodicals, Inc., Mass Spec Rev