Design and Preclinical Evaluation of Some Bone Seeking Radiopharmaceuticals for Medical Application

Skeletal scintigraphy (Radionuclide scanning) is a special type of nuclear medicine procedure that uses small amounts of radioactive material (radiotracers) to allows visualisation of bone metabolism or bone remodeling, while most other imaging techniques such as X-ray, computed tomography and CT cannot. Radionuclide scanning can image the function of the body at the molecular level and assess the severity of a variety of bone diseases and conditions, including fractures, infection and cancer. Additionally, it can be used for assessing the rate of bone graft healing. The radionuclide bone scan remains an excellent modality to detect metastatic disease in patients suffering from primary malignancies The proper isotope for labeling and imaging processes should have suitable short half life and suitable photon energy within the range of gamma camera. Iodine-123 and technetium-99 m are the most proper isotopes that fulfill these criteria. Selection either of them will be dependent on the structure of the compound to be labeled (ligand). Skeletal scintigraphy in humans is currently achieved by using Technetium-99 m labeled methylene diphosphonate (^99mTc-M D P), ethylene diamine tetra methylene phosphonate (^99mTc-E D T M P), dicarboxy propane diphosphonate (^99mTc-D P D), hydroxyl ethylidine diphosphonate (^99mTc-H E D P) and hydroxyl Methylenediphosphonate (^99mTc-H M D P). The main disadvantage of these ^99mTc labeled di phosphonates (D Ps) is an interval of 2–6 h is needed between injection and bone imaging. Shortening this interval would decrease the burden on patients in terms of the total length of the examination and the dose of radiation absorbed. To enable imaging at an earlier time after injection, a radiopharmaceutical with higher affinity for bone is required correspondingly. Tiludronate and a new zoledronate derivative were chosen as ligands for our new radiopharmaceuticals. They were evaluated for their ability to carry radionuclotide (^99mTc) to bone. The experimental part was focused on studying the reaction conditions that allow both drugs to be successfully labeled with ^99mTc. The biodistribution of radiolabeled drugs in mice body organs was studied and followed by pharmacokinetic analysis for the radiolabeled drugs in target organ (bone)