Mechanisms of Localization of Radiopharmaceuticals

The design of radiopharmaceuticals is based solely upon physiological function of the target organ. The mechanism of localization of a radiopharmaceutical in a particular target organ depends upon processes as varied as antigen-antibody reactions, physical trapping of particles, receptor site binding, removal of intentionally damaged cells from circulation, and transport of a chemical species across a cell membrane and into the cell by a normally operative metabolic process. Radiochemistry plays a significant part in the development of these compounds and methods of performing quality control to insure radiochemical purity.

1. Active Transport: involves use of a normally operative metabolic pathway in the body for moving a radiopharmaceutical across a cell membrane and into the cell. Example: I-131 NaI for thyroid imaging.

2. Phagocytosis: physical entrapment of colloidal particles by Kupffer cells in the RE System. Example: Tc-99m sulfur colloid for liver/spleen imaging.

3. Capillary blockade: intentional microembolization of a capillary bed with particles. Example: Tc-99m MAA for pulmonary perfusion imaging.

4. Cell Sequestration: Injection of damaged RBC's to produce a spleen scan with no visualization of the liver. Example: heat damaged autologous Tc-99m RBC's.

5. Simple/exchange diffusion: a mechanism whereby a radiotracer diffuses across cell membranes and then binds/attaches to a cell component. Example: F-18 NaF for bone imaging.

6. Compartmental Localization: placement of a radiotracer in a fluid space and imaging of that fluid space. Example: Tc-99m HSA for MUGA's, In-111 DTPA for cisternograms, Xe-133 gas for pulmonary perfusion.

7. Chemisorption: surface binding of radiopharmaceutical to a solid structure, e.g., In-111 platelets bound to surface of an active thrombus.

8. Antigen/antibody reaction: uptake at tumor site due to specific binding of radiolabeled antibody to surface antigens on tumors. Example: In-111 Oncoscint for localizationn of recurrent ovarian or colorectal carcinoma.

9. Receptor-binding: binding of radiopharmaceutical to high-affinity receptor sites. Example: In-111 octreotide for localization of neuroendocrine and other tumors based on binding of a somatostatin analog to receptor sites in tumors.