Radiologic agents for monitoring alzheimer's disease progression and Evaluating a Response to Therapy and processes for the preparation of such agents
View Patent ↗Disclosed are certain cycloSalingenyl pyrimidine nucleoside monophosphates comprising positron emitters or gamma-emitting radiohalides, uses thereof for monitoring Alzheimer's disease progression and evaluating response to therapy and process for their preparation.
1. A compound of the formula:
wherein R represents a substituted or unsubstituted, straight or branched chain, saturated or unsaturated hydrocarbyl (C 1 -C 15 ) group, radioactive halogen, non-radioactive halogen;
R a represents radioactive halogen, non-radioactive halogen, hydroxyl, one of R and Ra being radioactive halogen;
X represents hydrogen, non-radioactive halogen, radioactive halogen;
Y represents hydrogen, a straight or branched chain, substituted or unsubstituted, saturated or unsaturated hydrocarbyl (C 1 -C 4 ) group, and 11 C-containing analogues of said hydrocarbyl group; and
Z represents hydrogen, straight or branched chain, substituted or unsubstituted saturated or unsaturated hydrocarbyl (C 1 -C 4 ) group, and 11 C-containing analogues of said hydrocarbyl group.
2. The compound of claim 1 , wherein R represents straight chain alkyl (C 1 -C 8 ) or aryl; R a represents 18 F; X represents F; Y represents branched chain alkyl (C 1 -C 4 ); Z represents branched chain alkyl (C 1 -C 4 ).
3. The compound 5′-O-[cycloSaligenyl-3,5-di(tert-butyl)-6-fluoro]-3′-[ 18 F]fluoro thymidine monophosphate, according to claim 1 .
4. The compound 5′-O-[cycloSaligenyl-3,5-di(tert-butyl)-6-fluoro-2′,3′-deoxy-3′-fluoro-5-[ 125 I]iodouridine monophosphate, according to claim 1 .
5. A method for making an ante mortem diagnosis of Alzheimer's disease comprising:
a. administering to a patient suspected of having Alzheimer's disease a compound according to claim 1 in an amount of up to 20 mCi (up to 740 MBq) effective to bind to butyrylcholinesterase (BChE) present in the brain of said patient; and
b. detecting the amount of BChE bound by said compound.
6. The method of claim 5 , further comprising comparing the amount of BChE detected to a positive or negative control.
7. The method of claim 5 , wherein said detecting is carried out by imaging.
8. The method of claim 7 , wherein the imaging is positron emission tomography (PET) or single photon emission computed tomography (SPECT).
9. The method of claim 5 , wherein said compound is administered intravenously or intracarotid.
10. The method according to claim 6 , wherein steps (a) and (b) are repeated at least once after passage of a predetermined time interval, an increase in said radioactive drug uptake during said time interval being indicative of the progression of AD in said patient.
11. The method according to claim 6 , wherein steps (a) and (b) are repeated at least once after passage of a predetermined time interval during which AD therapy is administered to said patient, a decrease in said radioactive drug uptake being indicative of the effectiveness of said therapy.