Diagnostic radiopharmaceuticals for localization in target tissues exhibiting a regional pH shift relative to surrounding tissues

Claim 3

The method of claim 1 wherein the compound contains at least one amine group.

Claim 4

The method of claim 1 wherein the compound is a weak organic base and has a percent protein binding of less than ninety percent.

Claim 5

The invention of claim 3 wherein the partition coefficient of the compound has a positive charge of at least 100% in the range of 6.60 to 7.60 pH units.

Claim 6

The method of claim 1 wherein the compound is a ditertiary amine or a physiologically acceptable salt thereof, the ditertiary amine including at least one moiety having a radioactive element emitting γ, X-ray or positron radiation.

Claim 7

The method of claim 1 wherein the compound has the generic formula of: ##STR10## wherein Y is a bivalent alkyl radical of up to 3 carbon atoms, R 1 is an alkyl radical of up to 3 carbon atoms. R 2 is an alkyl radical of up to 3 carbon atoms and R 3 is an alkyl, substituted aminoalkyl, arylalkyl, cycloalkyl, or arylcycloalkyl radical of from 1 to 20 carbon atoms.

Claim 8

The method of claim 1 wherein the compound has the formula of: ##STR11## wherein n is an integer having the values of 1-10, R 1 is a mono or divalent alkyl radical of up to 3 carbon atoms, R 2 is a mono or divalent alkyl radical of up to 3 carbon atoms, m is an integer having the values of 0 or 1, x is independently at each occurrence --CH 2 --, O, S or Se and R 3 is an alkyl substituted aminoalkyl, arylalkyl, cycloalkyl, or arylcycloalkyl radical of from 1 to 20 carbon atoms.

Claim 9

The method of claim 1 wherein the compound has the formula: ##STR12## wherein Y is independently at each occurrence a bivalent alkyl radical of up to 3 carbon atoms, R 1 is independently at each occurrence an alkyl radical of up to 3 carbon atoms, and R 2 is independently at each occurrence an alkyl radical of up to 3 carbon atoms.

Claim 10

The method of claim 1 wherein the radiopharmaceutical compound has the formula of: ##STR13## wherein n is an integer having the values 1-10, R 1 is independently at each occurrence a mono or divalent alkyl radical of up to 3 carbon atoms, R 2 is independently at each occurrence a mono or divalent alkyl radical of up to 3 carbon atoms, m is an integer having the values 0 or 1, and X is independently at each occurrence --CH 2 --, O, S or Se.

Claim 11

The method of claim 9 wherein: n equals 2, R 1 is --CH 2 --CH 2 --, R 2 is --CH 2 --CH 2 --, m equals 1, and X is --CH 2 --.

Claim 12

The method of claim 9 wherein: n equals 2, R 1 is --CH 2 --CH 2 --, R 2 is --CH 2 --CH 2 --, m equals 1, and X is --O--.

Claim 13

A radiopharmaceutical method for observing at least one target tissue or organ of a mammal, the target tissue or organ having a physiologically significantly lower intracellular pH than the blood of the mammal, the method comprising the steps of: introducing a radiopharmaceutical compound into the bloodstream of the mammal, the compound containing at least one radioactive element, other than an isotope of iodine, emitting γ, X-ray or positron radiation detectable by radiation detecting means, the compound having a n-octanol-aqueous medium partition coefficient which is significantly dependent on pH of the aqueous medium at least in the pH range of 6.6 to 7.6 so that the n-octanol-aqueous medium partition coefficient of the compound increases with increasing pH at least in said pH range; said compound containing at least one amine group; allowing the compound to penetrate into cells of the target tissue or organ by diffusion through the cell membranes wherein due to the lower pH, the n-octanol-aqueous medium partition coefficient of the compound is significantly diminished whereby a rate of exit of the compound from the target tissue or organ by diffusion is significantly diminished compared to its rate of entry into the target tissue or organ, resulting in at least temporary accumulation of the compound in the target tissue or organ; and detecting with a radiation detecting means the accumulated compound in the target tissue or organ.

Claim 14

A radiopharmaceutical method for observing at least one target tissue or organ of a mammal, the target tissue or organ having a physiologically significantly lower intracellular pH than the blood of the mammal, the method comprising the steps of: introducing a radiopharmaceutical compound into the bloodstream of the mammal, the compound containing at least one radioactive element, other than an isotope of iodine, emitting γ, X-ray or positron radiation detectable by radiation detecting means, the compound having a n-octanol-aqueous medium partition coefficient which is significantly dependent on pH of the aqueous medium at least in the pH range of 6.6 to 7.6 so that the n-octanol-aqueous medium partition coefficient of the compound increases with increasing pH at least in said pH range; said compound containing at least one amine group; allowing the compound to penetrate into cells of the target tissue or organ by diffusion through the cell membranes wherein due to the lower pH, the n-octanol-aqueous medium partition coefficient of the compound is significantly diminished whereby a rate of exit of the compound from the target tissue or organ by diffusion is significantly diminished compared to its rate of entry into the target tissue or organ, resulting in at least temporary accumulation of the compound in the target tissue or organ; and detecting with a radiation detecting means the accumulated compound in the target tissue or organ.

Claim 15

The method of claim 12 wherein the compound is a weak organic base having at least one pKa in the range of 3.0-9.00.

Claim 16

The method of claim 12 wherein the compound is a selenide containing Se-75 isotope and at least one tertiary amine moiety.

Claim 17

The method of claim 12 wherein the target organ is the brain of the mammal.

Claim 18

The method of claim 12 wherein the target tissue is a tumor tissue.

Claim 19

The method of claim 12 wherein the target tissue is heart tissue.

Claim 20

The method of claim 12 wherein the target tissue is an abscess.

Claim 21

The method of claim 16 or 17 wherein the compound has the formula: ##STR14## wherein n is an integer having the values 1-10, R 1 is independently at each occurrence a mono or divalent alkyl radical of up to 3 carbon atoms, R 2 is independently at each occurrence a mono or divalent alkyl radical of up to 3 carbon atoms, m is an integer having the values 0 or 1, and X is independently at each occurrence --CH 2 --, O, S or Se.

Claim 22

The method of claim 19 wherein n equals 2, R 1 is --CH 2 --CH 2 --, R 2 is --CH 2 --CH 2 --, m equals 1, and X is --CH 2 --.

Claim 23

The method of claim 20 wherein n equals 2 R 1 is --CH 2 --CH 2 --, R 2 is --CH 2 --CH 2 --, m equals 1, and X is --O--.