Radiopharmaceuticals for brain imaging

Brain imaging is performed using radiopharmaceuticals by single photon emission computed tomography (SPECT) and positron emission tomography (PET). SPECT and PET radiopharmaceuticals are classified according to blood-brain-barrier permeability, cerebral perfusion and metabolism receptor-binding, and antigen-antibody binding. The blood-brain-barrier (BBB) SPECT agents, such as 99m TcO 4 − [ 99m Tc]DTPA, 201 Tl and [ 67 Ga]citrate are excluded by normal brain cells, but enter into tumor cells because of altered BBB. These agents were used in the earlier period for the detection of brain tumors. SPECT perfusion agents such as [ 123 I]IMP, [ 99m Tc]HMPAO, [ 99m Tc]ECD are lipophilic agents and therefore, diffuse into the normal brain. These tracers have been successfully used to detect various cerebrovascular diseases such as stroke, Parkinson disease, Huntington's disease, epilepsy, dementia, and psychiatric disorders. Xenon-133 and radiolabeled microspheres have been used for the measurement of cerebral blood flow (CBF). Important receptor-binding SPECT radiopharmaceuticals include [ 123 I]QNE, [ 123 I]IBZM, and [ 123 I]iomazenil. These tracers bind to specific receptors in the brain, thus displaying their distribution in various receptor-related cerebral diseases. Radioiodinated monoclonal antibodies were used for the detection of brain tumors. PET radiopharmaceuticals for brain imaging are commonly labeled with positron-emitters such as 11 C, 13 N, 15 O, and 18 F, although other radionuclides such as 82 Rb, 62 Cu and 68 Ga also were used. The brain uptake of [ 13 N]glutamate, [ 68 Ga]EDTA and [ 82 Rb]RbCl depends on the BBB permeability, but these are rarely used for brain imaging. Several cerebral perfusion agents have been introduced, of which [ 15 O]water, [ 13 N]ammonia, and [ 15 O]butanol have been used more frequently. Regional CBF has been quantitated by using these tracers in normal and different cerebral disease states. Other perfusion agents include [ 15 O]O 2 , [ 11 C]CO, [ 11 C[CO 2 , [ 18 F]fluoromethane, [ 15 O]O 2 , [ 11 C]butanol, and [ 62 Cu]PTSM. Among the PET cerebral metabolic agents, [ 18 F]fluoro-deoxyglucose (FDG) is most commonly used to detect metabolic abnormalities in the brain. Various brain tumors have been graded by [ 18 F]FDG PET. This technique was used to detect epileptic foci by showing increased uptake in the foci during the ictal period and decreased uptake in the interictal period. Differentiation between recurrent tumors and radiation necrosis and the detection of Alzheimer's disease have been made successfully by [ 18 F]FDG PET. Other PET metabolic agents such as [ 11 C]deoxyglucose, and [ 11 C]methylmethionine have drawn attention in the detection of brain tumors. [ 18 F]fluorodopa is a cerebral neurotransmitter agent, which has been found very useful in the detection of Parkinson disease that shows reduced uptake of the tracer in the striatum of the brain. The distribution of different receptors in the brain and their alteration in different disease states are assessed by using different receptor-binding PET radiotracers such as [ 11 C]methylspiperone, [ 18 F]fluoroethylspiperone, [ 18 fluoropropylspiperone, [ 11 C]carfentanil, [ 11 C]diprenorphine, [ 11 C]raclopride, [ 11 C]flumasenil, and so on.