31p NMR spectroscopy of mixed aqueous Na pyrophosphate and stannous chloride solutions. Evidence for pyrophosphate-Sn complex formation

Abstract

99mTc pyrophosphate and 99mTc organic phosphorus compounds have been widely used in recent years for bone scintigraphy. These compounds showed preferential uptake by the human skeleton which al lowed the external imaging of normal and pathological bones (1-5). The labeled pyrophosphate was usually prepared in two steps (6) at room temperature. Aqueous Na pyrophosphate solution was first m ixed with a stannous chloride solution. 99mTc eluted from a 99Mo generator was, then, added and the pharmaceutical was ready for intravenous injection. The mode of formation and the structure of the labeled pyrophosphate remained poorly understood. Three possibilities were proposed: (a) Sn(I1) ions reduce pertechnetate ions to a chemical form which allows the binding of Tc with pyrophosphate, (b) Sn(I1) ions are first bound to pyrophosphate, then, exchange with Tc in the appropriate chemical form, (c) a double Tc-Sn-pyrophosphate complex is formed. In the present work, we tried to determine the chemical reaction which occurred during the first step of the labeled compound preparation before adding pertechnetate ions. In a previous paper (7) ‘19Sn M iissbauer spectroscopy of the m ixed aqueous pyrophosphate stannous chloride solutions showed the presence of a pyrophosphate-Sn complex at 77 K. In the present work, 3’P NMR spectroscopy was used to confirm the presence of this complex at room temperature and to get information on its chemical structure. 31P Fourier transform NMR spectra were carried out with a Varian XL 100 spectrometer with an operating frequency of 40.5 MHz. D20 present as the bulk solvent provided the deuterium lock for field frequency stabilization. Data acquisition emp loyed a spectral width of 2500 Hz with 4096 accumulated data points and a pulse repetition rate of 1 Hz. The Fourier transform was carried out with a Varian 620 L 100 data processor and 4 K time doma in points providing a resolution of 1 Hz/point. Measurements were performed at 25°C on 2.0-ml samples contained in lo-mm diam sample tubes and with low-speed spinning. F ive hundred to one thousand transients were required to obtain each spectrum. Proton decoupl ing was used with a I-kHz noise bandwidth. Chemical shifts were expressed relative to an 85% H3P04 reference in D20, with shifts to higher frequency expressed as positive.