Receptors are found inside or on surface of human cells. Specific substances including alcohols, carbohydrates, amines, amino acids, peptides or proteins can bind to the receptors for communication between the cell and the outside world. Based on such property, the specific substances are connected to radioactive elements first. Then the radio-labeled compounds enter human bodies through the receptors and retain at specific organs or tissues. Thus the purposes of diagnostic imaging or disease treatment in the radiopharmaceutical field can be achieved.
The structural formula of the compound includes two different types of functional groups. One end of the compound is a functional group that forms a covalent bonding such as amide, thiourea, ester, alkylated amine, etc. The other end of the compound includes an electron provider such as nitrogen, oxygen, or sulfur able to transfer electrons to metals so as to form stable metal complexes. The bifunctional compound means the compound able to bind to specific substances and radioisotopes at the same time.
99mTc is present in more than 85% of currently available radiopharmaceuticals for diagnostic imaging. The design of Tc-99m radiopharmaceuticals is based on coordination chemistry of Technetium (Tc). Technetium forms various types of oxides with oxygen and technetium (V) oxide is the most stable. Technetium can easily form chemical bonds with atoms having lone pair of electrons such as nitrogen, sulfur, oxygen, etc in a ligand to form stable complexes with pyramidal geometry.
As to bonding of biochemical substances, the compound containing polybasic carboxylic acids is used for bonding to at least two substances. The bonding force between polybasic substances and the receptor is far more larger than the bonding force between a single substance and the receptor. For example, the affinity of a substance with three N-acetylgalactosamine (GaINAc) to asialo-glycoprotein receptor (ASGPR) on surface of liver cells is 106 times of the affinity of a substance with a single GaINAc. In order to increase the affinity between the substance and the receptor, the compound able to bind to polybasic substances can be used.
USPTO Backgrounds
USPTO Backgrounds