Comparison of 99mTc-labeled phosphate and phosphonate agents for skeletal imaging

The use of 99mTc-labeled phosphate and phosphonate compounds in place of 18F, 85Sr, and 87Sr for bone scintigraphy has become commonplace throughout the world in a relatively short time. The labeling of polyphosphate with 99mTc 4 years ago, followed rapidly by the introduction of 99mTc-labeled pyrophosphate for skeletal imaging, must therefore be regarded as a major contribution to the practice of diagnostic nuclear medicine. The markedly reduced patient radiation exposure and concomitant increase in photon detection efficiency derived from the more favorable physical decay characteristics of 99mTc led to increased sensitivity and resolution and in turn to improved diagnostic efficacy. The subsequent clinical use of the phosphonate complex 99mTc-HEDP represented a further modification of the same basic approach. Current clinical trials with 99mTc-labeled methylene diphosphonic acid (MDP), which appears to demonstrate enhanced biologic properties for scintigraphy of the osseous structures, is the latest example in this series of refinements. This article compares the technetium-labeled agents already in clinical use and, using animal data, contrasts them with several new multifunctional phosphonates and the novel inorganic compound sodium imidodiphosphate (IDP). In addition, an attempt is made to clarify the conflicting evidence in the nuclear medicine literature regarding the relationship between polyphosphate chain length and skeletal uptake.