B ring reduced-D ring oxidized tetrapyrrolic photosensitizers for photodynamic therapy and tumor imaging
Tetrapyrrolic photosensitizers and imaging agent compounds having A, B, C, and D rings and having a reduced B ring and an oxidized D ring. The compounds preferably have a purity of at least 95 percent and preferably have a fused system connected at an unsaturated carbon atom of the C ring nearest the D ring and at the unsaturated carbon atom between the C and D rings. The invention also includes a method of making the compounds at over 95 percent yield by starting with a B and D ring oxidized tetrapyrollic compound and dissolving it in a halogenated hydrocarbon solvent and treating it with sufficient nitroalkane solution of FeCl 3 6H 2 O to oxidize the D ring and separating the resulting organic layer and drying.
1. A tetrapyrrolic compound selected from the group consisting of:
wherein R is —COCH3 or —CH(OR 3 )CH 3 ; where R 3 is a saturated or unsaturated alkyl chain with 1-8 carbon atoms, polyethylene glycol (PEG) with carbon chain of 1-8 carbon atoms, or halogen (Cl, Br, I or F)-substituted phenyl ring containing saturated or unsaturated alkyl chain with 1-8 carbon atoms as a linker or the corresponding I-124, I-125, I-131 or F-18 radionuclide;
R 1 is COOH or COOR 4 where R 4 is C 1-8 alkyl or substituted C 1-8 alkyl;
R 2 is O or N—R 5 where R 5 is C 1-8 alkyl; and
M is 2H, Ga, Pd, Al, Zn, Cu or the radioisotopes of Ga, Pd, Al, Zn, and Cu for positron emission tomography (PET) or single-photon emission computed tomography (SPEDT).
2. The compound of claim 1 having wavelength absorption in the range of 660 to 750 nm.
3. The compound of claim 1 having a purity of at least 95 percent.
4. A method of making the compound of claim 1 at over 95 percent yield by starting with a B and D ring reduced tetrapyrrolic compound and dissolving it in a halogenated hydrocarbon solvent and treating it with sufficient nitroalkane solution of FeCl 3 6H 2 O to oxidize the D ring and separating the resulting organic layer and drying.
5. The method of claim 4 wherein a B and D ring reduced chlorin is treated to obtain a B ring reduced -D ring oxidized chlorin.
6. The method of claim 5 where the starting tetrapyrrolic compound is methyl bacteriopyropheophorbide-a.
7. The method of claim 5 where the starting tetrapyrrolic compound is bacteriochlorophyll-a.
8. A method for imaging tumors comprising injecting a compound according to claim 1 into a subject and imaging using PET, SPECT, or fluorescence.