Uptake and Biodistribution of Technetium-99m-MD32P During Rat Tibia! Bone Repair

suggested that circulating 99mTc.MDP is adsorbed selec tively onto the mineral phase of forming bone (via hy droxyapatite crystals). This is based on studies carried out in vivo, in which the use of autoradiographic techniques localized the 99mTc to mineralized tissue and not to the unmineralized osteoid or bone cells (13,14). In vitro stud ies using calcifying solutions support this finding in that they indicate that the 99mTc is adsorbed onto the hydro xyapatite nuclei that are being formed (15,16). It hasalsobeensuggested that the collagenmatrix of bone is the target for 99mTc(12,1 7). This is based on the observation of its increased uptake by bones in osteoma lacia, Paget's disease and hyperparathyroidism when ad ministered as 99mTc@pyrophosphate. These diseases are characterized by the accumulation of large quantities of immature collagen. Phosphate-containing enzymes which are present in large quantities in bone (e.g. alkaline phos phatase) have also been suggested to be the binding sites for 99mTc(11). A major role in the kinetics of 99mTc@phosphate uptake in bone is played by its local vascularity, with localization of 99mTcphosphatase being marked at highly vascularized bone surfaces (19). An example for this mechanism is the high uptake of the radionuclide in the cartilage bars asso ciated with the vascular loops of the growth plate (20). In addition, autoradiographic studies demonstrate that the distribution of pyrophosphate in bone reflects the distri bution ofthe blood supply (1,21,22). There is still a debate in the literature as to whether this radiopharmaceutical is transported to the bone intact, or whether it is hydrolysed during its transport to the bone. Most investigators believe that the injected radiolabeled complex is transported to the bone where it is deposited (3,5,18,26). A number ofarticles have indicated that the radiolabeled complex is hydrolyzed into its components and that the individual components are taken up by the bone (27â€”29). It has been demonstrated that osteogenesis after injury to the rat tibial bone could serve as a model for investigat ing the uptake mechanism of labeled 99mTc@phosphates (30). This is a highly reproducible model of bone healing, which is triggered by ablation of the tibial bone marrow and whose stages of healing are clearly definable (31,32). The present study was earned out in order to test the hy pothesis that intravenously injected Tc-MDP separates into its technetium and methylene diphosphonate components in the bone, and that the technetium is preferentially taken-up by the newly-formed osteoid, while the methylene diphospho nate is taken up by the forming mineral. Uptake of Tc-MDP was studied in a rat model of primary bone formation following tibial bone marrow ablation. Eachoffive radiopharmaceuticals (Â°@Tco4, @Tc-MDP, Tc-MD@P,Â°@Tc-MD@P or MD@P)was injected and their uptake was followed in the whole bone as well as in the organic and inorganic phases of the bone. Irrespective of the radionuclides injected, Â°@â€œTc was always taken-up preferentially by the organic phase, while the @P was preferentiallytaken-up by the inorganicphase. When @Â°â€œTcO4 was injected,it was not taken up by the boneat all. These results indicate that the increased incorporation of @Â°â€œTc, when administered as Â°@â€œTc-MDP during bone healing, reflectsanenhancementintheformationof theorganicmatrix and not of the calcification process. The study also suggests that the @â€œTc-MDP dissociates into its technetium and meth ylene diphosphonate moieties, which are then adsorbed onto the organicand inorganicphasesrespectively.