New bone scanning agent: 99m Tc-labeled 1-hydroxy-ethylidene-1, 1-disodium phosphonate.

Structure The radionuclide 99mTchas nearly ideal physical characteristics for imaging and is presently being used as a label for numerous radiopharmaceuticals. Consequently, most of the major organ systems have been studied with the aid of this radionuclide. One of the most recent to be considered is the skeletal system as reported by Subramanian and coworkers who labeled inorganic polyphosphates with oDmTc and observed satisfactory bone images (1,2). Our laboratory is presently investigating several organo-phosphorus compounds which also show promise as satisfactory bone imaging agents after tag ging with 99mTc One such compound which currently shows the most promise is a phosphonate derivative with the chemical name 1-hydroxy-ethylidene-1, 1-disodium phosphonate (HEDSPA) . Phosphonates are compounds containing a carbon-to-phosphate bond, and diphosphonates are compounds containing a carbon-to-disphosphate bond (3) . The structures of several inorganic and organic phosphorus corn pounds are shown in Table 1. Phosphonates have been used both in industry and in medicine : for example, as additives to deter gent tablets (4) , as scale and corrosion inhibitors (5), and as antioxidants (6). In 1966 several phos phonates were found to significantly inhibit bone resorption in vivo (7) , and three years later Fleisch and coworkers reported diphosphonates to inhibit the dissolution and crystal growth of hydroxyapatite (8) . More recently, diphosphonates have shown promise in the clinic for the treatment of myositis ossificans progressiva (9,10) , Paget's disease (11), and calcinosis universalis (12). This paper describes the synthesis and quality control of 1-hydroxy-ethy!idene-1 , 1-diphosphonic acid (HEDPHA), and the formulation and quality control of oomTc@HEDSPA.