US 8,372,380 B2Granted

In vivo imaging of sulfotransferases

AssigneeThe Regents of the University of California

InventorsJorge R. Barrio, Vladimir Kepe, Gary W. Small, Nagichettiar Satyamurthy

Life of this patent

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Abstract

Radiolabeled tracers for sulfotransferases (SULTs), their synthesis, and their use are provided. Included are substituted phenols, naphthols, coumarins, and flavones radiolabeled with 18F, 123I, 124I, 125I, or 11C. Also provided are in vivo techniques for using these and other tracers as analytical and diagnostic tools to study sulfotransferase distribution and activity, in health and disease, and to evaluate therapeutic interventions.

Claims23

Dependent claims

A method of assessing sulfotransferase (SULT) distribution or activity in a mammal, in vivo, comprising:

administering to the mammal a bolus of a radiolabeled tracer;
generating radiographic data indicative of tracer uptake in the mammal by scanning the mammal using a radiographic technique;
and
using the radiographic data to assess SULT distribution or activity in the mammal;
wherein the radiolabeled tracer comprises at least one compound selected from the group consisting of
(a) phenols having the formula (1)
where A1 is OH and each of A2-A6 is independently selected from the group of moieties denoted by “K” (defined below), provided that at least one of A2-A6 is or contains a radioisotope;
or A1 and A3 are both OH and each of A2, A4-A6 is independently selected from the group of moieties denoted by K, provided that at least one of A2, A4-A6 is or contains a radioisotope;
(b) naphthols having the formula (2)
where B1 is OH and each of B2-B8 is independently selected from the group of moieties denoted by K, provided that at least one of B2-B8 is or contains a radioisotope;
or B2 is OH and each of B1, B3-B8 is independently selected from the group of moieties denoted by K, provided that at least one of B1, B3-B8 is or contains a radioisotope;
or B1 and B3 are each OH and each of B2, B4-B8 is independently selected from the group of moieties denoted by K, provided that at least one of B4-B8 is or contains a radioisotope;
(c) coumarins having the formula (3)
where X and Y are, independently, O, S, or N—R1 (wherein R1 is H, alkyl, aryl, [11C]methyl, [18F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [124I]iodoalkyl, [124I]iodoaryl,] [125I]iodoalkyl, or [125I]iodoaryl);
and wherein
C3 is OH and each of C1-C2, C4-C6 is independently selected from the group of moieties denoted by K;
or
C4 is OH and each of C1-C3, C5-C6 is independently selected from the group of moieties denoted by K;
or
C5 is OH and each of C1-C4, C6 is independently selected from the group of moieties denoted by K;
or
C6 is OH and each of C1-C5 is independently selected from the group of moieties denoted by K;
or
C2 and C3═OH and each of C1, C4-C6 is independently selected from the group of moieties denoted by K;
or
C2 and C4═OH and each of C1, C3, C5-C6 is independently selected from the group of moieties denoted by K;
or
C2 and C5═OH and each of C1, C3-C4, C6 is independently selected from the group of moieties denoted by K;
or
C2 and C6═OH and each of C1, C3-C5 is independently selected from the group of moieties denoted by K;
or
C3 and C5═OH and each of C1-C2, C4, C6 is independently selected from the group of moieties denoted by K;
or
C4 and C6═OH and each of C1-C3, C5 is independently selected from the group of moieties denoted by K;
or
C2═C3═C5═OH and each of C1, C4, C6 is independently selected from the group of moieties denoted by K;
or
C2, C4 and C6═OH and each of C1, C3, C5 is independently selected from the group of moieties denoted by K;
wherein in each case at least one of C1-C6, X, or Y is or contains a radioisotope;
(d) flavones having the formula (4)
where X and Y are, independently, O, S, or N—R1 (wherein R1 is H, alkyl, aryl, [11C]methyl, [18F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [124]iodoalkyl, [124I]iodoaryl,] [125I]iodoalkyl, or [125I]iodoaryl);
and wherein
D3 is OH and each of D1-D2, D4-D6 is independently selected from the group of moieties denoted by K;
or
D4 is OH and each of D1-D3, D5-D6 is independently selected from the group of moieties denoted by K;
or
D5 is OH and each of D1-D4, D6 is independently selected from the group of moieties denoted by K;
or
D6 is OH and each of D1-D5 is independently selected from the group of moieties denoted by K;
or
D2 and D3 are OH and each of D1, D4-D6 is independently selected from the group of moieties denoted by K;
or
D2 and D4 are OH and each of D1, D3, D5-D6 is independently selected from the group of moieties denoted by K;
or
D2 and D5 are OH and each of D1, D3-D4, D6 is independently selected from the group of moieties denoted by K;
or
D2 and D6 are OH and each of D1, D3-D5 is independently selected from the group of moieties denoted by K;
or
D3 and D5 are OH and each of D1-D2, D4, D6 is independently selected from the group of moieties denoted by K;
or
D4 and D6 are OH and each of D1-D3, D5 is independently selected from the group of moieties denoted by K;
or
D2, D3 and D5 are OH, and D1, D4, D6 is independently selected from the group of moieties denoted by K;
or
D2, D4 and D6 are OH, and D1, D3, D5 is independently selected from the group of moieties denoted by K;
wherein in each case at least one of D1-D6, X, or Y is or contains a radioisotope;
(e) fused ring compounds having the formula (5)
where Z is O, S, N—R1 (wherein R1 is H, alkyl, aryl, [11C]methyl, [18F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [1241]iodoalkyl, [1241]iodoaryl,] [125I]iodoalkyl, or [125I]iodoaryl), CH2, or CH═CH;
and W is N or CH;
and wherein
E2 is OH and each of E1, E3-E5 is independently selected from the group of moieties denoted by K;
or
E3 is OH and each of E1-E2, E4-E5 is independently selected from the group of moieties denoted by K;
or
E4 is OH and each of E1-E3, E5 is independently selected from the group of moieties denoted by K;
or
E5 is OH and each of E1-E4 is independently selected from the group of moieties denoted by K;
or
E2 and E4 are OH and each of E1-E4 is independently selected from the group of moieties denoted by K;
or
E3 and E5 are OH and each of E1, E2, E4, is independently selected from the group of moieties denoted by K;
and wherein in each case at least one of E1-E5 or Z is or contains a radioisotope;
(e′) structurally related fused ring compounds in which E1 is a substituted aryl group, said compounds having the formula 5a:
where Z is O, S, N—R1 (wherein R1 is H, alkyl, aryl, [11C]methyl, [18F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [124I]iodoalkyl, [124I]iodoaryl,] [125I]iodoalkyl, or [125I]iodoaryl), CH2, or CH═CH;
W is N or CH;
and P is H, alkyl, aryl, [11C]methyl, 18F, [18F]fluoroalkyl, [18F]fluoroaryl, 123I, [123I]iodoalkyl, [123I]iodoaryl, 124I, [124I]iodoalkyl, [124I]iodoaryl,] 125I, [125I]iodoalkyl, or [125I]iodoaryl);
and wherein E2 is OH and each of E3-E5 is independently selected from the group of moieties denoted by K;
or
E3 is OH and each of E2, E4-E5 is independently selected from the group of moieties denoted by K;
or
E4 is OH and each of E2-E3, E5 is independently selected from the group of moieties denoted by K;
or
E5 is OH and each of E2-E4 is independently selected from the group of moieties denoted by K;
or
E2 and E4 are OH and each of E3, E5 is independently selected from the group of moieties denoted by K;
or
E3 and E5 are OH and each of E2, E4 is independently selected from the group of moieties denoted by K;
wherein in each case at least one of E1-E5, I′, or Z is or contains a radioisotope;
and wherein R′ is selected from the group consisting of H, NH—CH3, N(CH3)2 NH2, OCH3, NH—CO—CH3, F, I, CN, NO2, SO2—CH3, and radiolabeled isotopes thereof;
(f) imidazopyridines having the formula (6):
where F1-F5 are the same as E1-E5, and wherein at least one of F1-F5 is or contains a radioisotope;
or
(g) stilbenes having the formula (7):
where W1 and W2 are, independently, alkyl, aryl, or OH;
and wherein
G3 is OH and each of G1-G2, G4-G10 is independently selected from the group of moieties denoted by K;
or
G2 and G4 are OH and each of G1, G3, G5-G10 is independently selected from the group of moieties denoted by K;
or
G3 and G8 are OH and each of G1-G3, G4-G7, G9-G10 is independently selected from the group of moieties denoted by K;
or
G2=G4=G8═OH and each of G1, G3, G5-G7, G9-G10 is independently selected from the group of moieties denoted by K;
and wherein in each case at least one of G1-G10 is or contains a radioisotope;
and wherein, in each of compounds (a)-(g), K is selected from the group consisting of H;
alkyl;
aryl;
18F;
[18F]fluoroalkyl;
[18F]fluoroaryl;
123I;
[123I]iodoalkyl;
[123I]iodoaryl;
124I;
[124I]iodoalkyl;
[124I]iodoaryl;
125I;
[125I]iodoalkyl;
[125I]iodoaryl;
—SR1, or —NR1R2 (where R1 and R2 are independently H, alkyl, aryl, [11C]methyl, [18F]fluoroalkyl;
[18F]fluoroaryl;
[123I]iodoalkyl;
[123I]iodoaryl;
[124I]iodoalkyl;
[124I]iodoaryl;
[125I]iodoalkyl;
or [125I]iodoaryl);
—NO2;
—CN;
—S(═O)—R3 or —S(═O)2—R3 (where R3 is alkyl, aryl, [11C]methyl, [18F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [124I]iodoaryl, [125I]iodoalkyl, [125I]iodoaryl), or —OR4, —NR4R5, (wherein R4 and R5 are independently H, alkyl, aryl, [11C]methyl, [18F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [124]iodoalkyl, [124]iodoaryl, [125I]iodoalkyl, or [125I]iodoaryl));
and —OC(═O)—R6, —SC(═O)—R6, or —NH—C(═O)—R6 (where R6 is alkyl, aryl, [11C]methyl, [18F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [124I]iodoalkyl, [124I]iodoaryl, [125I]iodoalkyl, or [125I]iodoaryl).

137 more elements

A method of evaluating therapeutic effect of an agent on a sulfotransferase in a mammal, comprising:

(A) administering a radiolabeled tracer to a mammal;
generating a first set of radiographic data by scanning the mammal using a radiographic technique;
administering an actual or putative therapeutic agent to the mammal, intravenously, orally, or by other suitable mode of delivery;
generating a second set of radiographic data by scanning the mammal using a radiographic technique;
and
comparing the first and second sets of radiographic data;
or
(B) administering an actual or putative therapeutic agent to the mammal, intravenously, orally, or by other suitable mode of delivery;
administering a radiolabeled tracer to the mammal;
generating a set of radiographic data by scanning the mammal using a radiographic technique;
and
comparing the set of radiographic data to data obtained in the absence of the agent;
wherein in (A) and (B) the radiolabeled tracer comprises at least one compound selected from the group consisting of
(a) phenols having the formula (1)
where A1 is OH and each of A2-A6 is independently selected from the group of moieties denoted by “K” (defined below), provided that at least one of A2-A6 is or contains a radioisotope;
or A1 and A3 are both OH and each of A2, A4-A6 is independently selected from the group of moieties denoted by K, provided that at least one of A2, A4-A6 is or contains a radioisotope;
(b) naphthols having the formula (2)
where B1 is OH and each of B2-B8 is independently selected from the group of moieties denoted by K, provided that at least one of B2-B8 is or contains a radioisotope;
or B2 is OH and each of B1, B3-B8 is independently selected from the group of moieties denoted by K, provided that at least one of B1, B3-B8 is or contains a radioisotope;
or B1 and B3 are each OH and each of B2, B4-B8 is independently selected from the group of moieties denoted by K, provided that at least one of B4-B8 is or contains a radioisotope;
(c) coumarins having the formula (3)
where X and Y are, independently, O, S, or N—R1 (wherein R1 is H, alkyl, aryl, [11C]methyl, [18F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [124I]iiodoalkyl, [124]iodoaryl,] [125I]iodoalkyl, or [125I]iodoaryl);
and wherein
C3 is OH and each of C1-C2, C4-C6 is independently selected from the group of moieties denoted by K;
or
C4 is OH and each of C1-C3, C5-C6 is independently selected from the group of moieties denoted by K;
or
C5 is OH and each of C1-C4, C6 is independently selected from the group of moieties denoted by K;
or
C6 is OH and each of C1-C5 is independently selected from the group of moieties denoted by K;
or
C2 and C3═OH and each of C1, C4-C6 is independently selected from the group of moieties denoted by K;
or
C2 and C4═OH and each of C1, C3, C5-C6 is independently selected from the group of moieties denoted by K;
or C2 and C5═OH and each of C1, C3-C4, C6 is independently selected from the group of moieties denoted by K;
or
C2 and C6═OH and each of C1, C3-C5 is independently selected from the group of moieties denoted by K;
or
C3 and C5═OH and each of C1-C2, C4, C6 is independently selected from the group of moieties denoted by K;
or
C4 and C6═OH and each of C1-C3, C5 is independently selected from the group of moieties denoted by K;
or
C2═C3═C5═OH and each of C1, C4, C6 is independently selected from the group of moieties denoted by K;
or
C2, C4 and C6═OH and each of C1, C3, C5 is independently selected from the group of moieties denoted by K;
wherein in each case at least one of C1-C6, X, or Y is or contains a radioisotope;
(d) flavones having the formula (4)
where X and Y are, independently, O, S, or N—R1 (wherein R′ is H, alkyl, aryl, [11C]methyl, [18F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [124I]iodoalkyl, [124I]iodoaryl,] [125I]iodoalkyl, or [125I]iodoaryl);
and wherein
D3 is OH and each of D1-D2, D4-D6 is independently selected from the group of moieties denoted by K;
or
D4 is OH and each of D1-D3, D5-D6 is independently selected from the group of moieties denoted by K;
or
D5 is OH and each of D1-D4, D6 is independently selected from the group of moieties denoted by K;
or
D6 is OH and each of D1-D5 is independently selected from the group of moieties denoted by K;
or
D2 and D3 are OH and each of D1, D4-D6 is independently selected from the group of moieties denoted by K;
or
D2 and D4 are OH and each of D1, D3, D5-D6 is independently selected from the group of moieties denoted by K;
or D2 and D5 are OH and each ofD1, D3-D4, D6 is independently selected from the group of moieties denoted by K;
or
D2 and D6 are OH and each of D1, D3-D5 is independently selected from the group of moieties denoted by K;
or
D3 and D5 are OH and each of D1-D2, D4, D6 is independently selected from the group of moieties denoted by K;
or
D4 and D6 are OH and each of D1-D3, D5 is independently selected from the group of moieties denoted by K;
or
D2, D3 and D5 are OH, and D1, D4, D6 is independently selected from the group of moieties denoted by K;
or
D2, D4 and D6 are OH, and D1, D3, D5 is independently selected from the group of moieties denoted by K;
(e) fused ring compounds having the formula (5)
where Z is O, S, N—R1 (wherein R1 is H, alkyl, aryl, [11C]methyl, [18F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [23I]iodoaryl, [124I]iodoalkyl, [124I]iodoaryl,] [125I]iodoalkyl, or [125I]iodoaryl), CH2, or CH—CH;
and W is N or CH;
and wherein
E2 is OH and each of E1, E3-E5 is independently selected from the group of moieties denoted by K;
or
E3 is OH and each of E1-E2, E4-E5 is independently selected from the group of moieties denoted by K;
or
E4 is OH and each of E1-E3, E5 is independently selected from the group of moieties denoted by K;
or
E5 is OH and each of E1-E4 is independently selected from the group of moieties denoted by K;
or
E2 and E4 are OH and each of E1-E4 is independently selected from the group of moieties denoted by K;
or
E3 and E5 are OH and each of E1, E2, E4, is independently selected from the group of moieties denoted by K;
and wherein in each case at least one of E1-E5 or Z is or contains a radioisotope;
(e′) structurally related fused ring compounds in which E1 is a substituted aryl group, said compounds having the formula 5a:
where Z is O, S, N—R1 (wherein R1 is H, alkyl, aryl, [11C]methyl, [18F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [[124]iodoalkyl, [124]iodoaryl,] [125I]iodoalkyl, or [125I]iodoaryl), CH2, or CH═CH;
W is N or CH;
and I1 is H, alkyl, aryl, [11C]methyl, 18F, [18F]fluoroalkyl, [18F]fluoroaryl, 123I, [123I]iodoalkyl, [123I]iodoaryl, 124I, [124]iodoalkyl, [124]iodoaryl,] 125I, [125I]iodoalkyl, or [125I]iodoaryl);
and wherein E2 is OH and each of E3-E5 is independently selected from the group of moieties denoted by K;
or
E3 is OH and each of E2, E4-E5 is independently selected from the group of moieties denoted by K;
or
E4 is OH and each of E2-E3, E5 is independently selected from the group of moieties denoted by K;
or
E5 is OH and each of E4 is independently selected from the group of moieties denoted by K;
or
E2 and E4 are OH and each of E3, E5 is independently selected from the group of moieties denoted by K;
or
E3 and E5 are OH and each of E2, E4 is independently selected from the group of moieties denoted by K;
wherein in each case at least one of E1-E5, I′, or Z is or contains a radioisotope;
and wherein R′ is selected from the group consisting of H, NH—CH3, N(CH3)2, NH2, OCH3, NH—CO—CH3, F, I, CN, NO2, SO2—CH3, and radiolabeled isotopes thereof;
(f) imidazopyridines having the formula (6):
where F1-F5 are the same as E1-E5, and wherein at least one of F1-F5 is or contains a radioisotope;
or
(g) stilbenes having the formula (7):
where W1 and W2 are, independently, alkyl, aryl, or OH;
and wherein
G3 is OH and each of G1-G2, G4-do is independently selected from the group of moieties denoted by K;
or
G2 and G4 are OH and each of G1, G3, G5-Gi0 is independently selected from the group of moieties denoted by K;
or
G3 and G8 are OH and each of G1-G3, G4-G7, G9-G10 is independently selected from the group of moieties denoted by K;
or
G2=G4=G8═OH and each of G1, G3, G5-G7, G9-G10 is independently selected from the group of moieties denoted by K;
and wherein in each case at least one of G1-G10 is or contains a radioisotope;
wherein in each case (a)-(g) K is selected from the group consisting of H;
alkyl;
aryl;
18F;
[18F]fluoroalkyl;
[18F]fluoro aryl;
123I;
[123I]iodoalkyl;
[123I]iodoaryl;
124I;
[124I]iodoalkyl;
[124I]iodoaryl;
125I;
[125I]iodoalkyl;
[125I]iodoaryl;
—SR1, or —NR1R2 (where R1 and R2 are independently H, alkyl, aryl, [11C]methyl, [18F]fluoroalkyl;
[18F]fluoroaryl;
[123I]iodoalkyl;
[123I]iodoaryl;
[124I]iodoalkyl;
[124I]iodoaryl;
125I] iodoalkyl;
or [125I]iodoaryl);
—NO2;
—CN;
—S(═O)—R3 or —S(═O)2—R3 (where R3 is alkyl, aryl, [11C]methyl, [18F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [124I]iodoalkyl, [124I]iodoaryl, [125I]iodoalkyl, [125I]iodoaryl), or —OR4, —NR4R5, (wherein R4 and R5 are independently H, alkyl, aryl, [11C]methyl, [18F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [124I]iodoalkyl, [124I]iodoaryl, [125I]iodoalkyl, or [125I]iodoaryl));
and —OC(═O)—R6, —SC(═O)—R6, or —NH—C(═O)—R6 (where R6 is alkyl, aryl, [11C]methyl, [18F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [124I]iodoalkyl, [124I]iodoaryl, [125I]iodoalkyl, or [125I]iodoaryl).

142 more elements

A method of monitoring sulfotransferase activity in a mammal, in vivo, comprising:

administering to a mammal a bolus of a first radiolabeled tracer;
generating first radiographic data indicative of first tracer uptake in the mammal by scanning the mammal using a radiographic technique;
administering to the mammal a bolus of a second radiolabeled tracer;
generating second radiographic data indicative of second tracer uptake in the mammal by scanning the mammal using a radiographic technique;
and
comparing the first radiographic data to the second radiographic data.

3 more elements

A radiolabeled tracer for sulfotransferase, comprising at least one compound selected from the group consisting of

(a) phenols having the formula (1)
where A1 is OH and each of A2-A6 is independently selected from the group of moieties denoted by “K” (defined below), provided that at least one of A2-A6 is or contains a radioisotope;
or A1 and A3 are both OH and each of A2, A4-A6 is independently selected from the group of moieties denoted by K, provided that at least one of A2, A4-A6 is or contains a radioisotope;
(b) naphthols having the formula (2)
where B1 is OH and each of B2-B8 is independently selected from the group of moieties denoted by K, provided that at least one of B2-B8 is or contains a radioisotope;
or B2 is OH and each of B1, B3-B8 is independently selected from the group of moieties denoted by K, provided that at least one of B1, B3-B8 is or contains a radioisotope;
or B1 and B3 are each OH and each of B2, B4-B8 is independently selected from the group of moieties denoted by K, provided that at least one of B4-B8 is or contains a radioisotope;
(c) coumarins having the formula (3)
where X and Y are, independently, O, S, or N—R′ (wherein R1 is H, alkyl, aryl, [11C]methyl, [18F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [124I]iodoalkyl, [124I]iodoaryl,] [125I]iodoalkyl, or [125I]iodoaryl);
and wherein
C3 is OH and each of C1-C2, C4-C6 is independently selected from the group of moieties denoted by K;
or
C4 is OH and each of C1-C3, C5-C6 is independently selected from the group of moieties denoted by K;
or
C5 is OH and each of C1-C4, C6 is independently selected from the group of moieties denoted by K;
or
C6 is OH and each of C1-C5 is independently selected from the group of moieties denoted by K;
or
C2 and C3═OH and each of C1, C4-C6 is independently selected from the group of moieties denoted by K;
or
C2 and C4═OH and each of C1, C3, C5-C6 is independently selected from the group of moieties denoted by K;
or
C2 and C5═OH and each of C1, C3-C4, C6 is independently selected from the group of moieties denoted by K;
or
C2 and C6═OH and each of C1, C3-C5 is independently selected from the group of moieties denoted by K;
or
C3 and C5═OH and each of C1-C2, C4, C6 is independently selected from the group of moieties denoted by K;
or
C4 and C6═OH and each of C1-C3, C5 is independently selected from the group of moieties denoted by K;
or
C2═C3═C5═OH and each of C1, C4, C6 is independently selected from the group of moieties denoted by K;
or
C2, C4 and C6═OH and each of C1, C3, C5 is independently selected from the group of moieties denoted by K;
wherein in each case at least one of C1-C6, X, or Y is or contains a radioisotope;
(d) flavones having the formula (4)
where X and Y are, independently, O, S, or N—R1 (wherein R1 is H, alkyl, aryl, [11C]methyl, [18F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [124I]iodoalkyl, [124I]iodoaryl,] [125I]iodoalkyl, or [125I]iodoaryl);
and wherein
D3 is OH and each of D1-D2, D4-D6 is independently selected from the group of moieties denoted by K;
or
D4 is OH and each of D1-D3, D5-D6 is independently selected from the group of moieties denoted by K;
or
D5 is OH and each of D1-D4, D6 is independently selected from the group of moieties denoted by K;
or
D6 is OH and each of D1-D5 is independently selected from the group of moieties denoted by K;
or
D2 and D3 are OH and each of D1, D4-D6 is independently selected from the group of moieties denoted by K;
or
D2 and D4 are OH and each of D1, D3, D5-D6 is independently selected from the group of moieties denoted by K;
or
D2 and D5 are OH and each of D1, D3-D4, D6 is independently selected from the group of moieties denoted by K;
or
D2 and D6 are OH and each of D1, D3-D5 is independently selected from the group of moieties denoted by K;
or
D3 and D5 are OH and each of D1-D2, D4, D6 is independently selected from the group of moieties denoted by K;
or
D4 and D6 are OH and each of D1-D3, D5 is independently selected from the group of moieties denoted by K;
or
D2, D3 and D5 are OH, and D1, D4, D6 is independently selected from the group of moieties denoted by K;
or
D2, D4 and D6 are OH, and D1, D3, D5 is independently selected from the group of moieties denoted by K;
wherein in each case at least one of D1-D6, X, or Y is or contains a radioisotope;
and wherein K is selected from the group consisting of H;
alkyl;
aryl;
18F;
[18F]fluoroalkyl;
[18F]fluoro aryl;
123I;
[123I]iodoalkyl;
[123I]iodoaryl;
124I;
[124I]iodoalkyl;
[124I]iodoaryl;
125I;
[125I]iodoalkyl;
[125I]iodoaryl;
—OR1, —SR1, or —NR1R2 (where R1 and R2 are independently H, alkyl, aryl, [α]methyl, [18F]fluoroalkyl;
[18F]fluoroaryl;
[123I]iodoalkyl;
[123I]iodoaryl;
[124I]iodoalkyl;
[124I]iodoaryl;
[125I]iodoalkyl;
or [125I]iodoaryl);
—NO2;
—CN;
—S(═O)—R3 or —S(═O)2—R3 (where R3 is alkyl, aryl, [11C]methyl, [118F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [124I]iodoalkyl, [124I]iodoaryl, [125I]iodoalkyl, [125I]iodoaryl), or —OR4, —NR4R5, (wherein R4 and R5 are independently H, alkyl, aryl, [11C]methyl, [18F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [124I]iodoalkyl, [124I]iodoaryl, [125I]iodoalkyl, or [125I]iodoaryl));
and —OC(═O)—R6, —SC(═O)—R6, or —NH—C(═O)—R6 (where R6 is alkyl, aryl, [11C]methyl, [1F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [124I]iodoalkyl, [124I]iodoaryl, [125I]iodoalkyl, or [125I]iodoaryl).

85 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/594,197Filed 31 Mar 2008 · us provisional application
Priority: 30 Mar 2007
Published: US 2010/0135906 A13 Jun 2010
Granted: 12 Feb 2013
Term ends: Not estimatedThe source records don’t support an estimate.

Classification9 codes

A61K 51/04
Characterised by the carrier , i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus: organic compounds
A61B 5/4088
Diagnosing or monitoring particular conditions of the nervous system: diagnosing of monitoring cognitive diseases, e.g. Alzheimer, prion diseases…
A61B 5/411
Detecting, measuring or recording for evaluating the immune or lymphatic systems: detecting or monitoring allergy or intolerance reactions to an…
A61K 31/57
Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids: substituted in position 17 beta by a chain…

Family

Application60/920,875Us provisional application · filed 30 Mar 2007
US 2010/0135906 A1Pre-grant publication · published 3 Jun 2010
US 8,372,380 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A method of assessing sulfotransferase (SULT) distribution or activity in a mammal, in vivo, comprising:

administering to the mammal a bolus of a radiolabeled tracer;
generating radiographic data indicative of tracer uptake in the mammal by scanning the mammal using a radiographic technique;
and
using the radiographic data to assess SULT distribution or activity in the mammal;
wherein the radiolabeled tracer comprises at least one compound selected from the group consisting of
(a) phenols having the formula (1)
where A1 is OH and each of A2-A6 is independently selected from the group of moieties denoted by “K” (defined below), provided that at least one of A2-A6 is or contains a radioisotope;
or A1 and A3 are both OH and each of A2, A4-A6 is independently selected from the group of moieties denoted by K, provided that at least one of A2, A4-A6 is or contains a radioisotope;
(b) naphthols having the formula (2)
where B1 is OH and each of B2-B8 is independently selected from the group of moieties denoted by K, provided that at least one of B2-B8 is or contains a radioisotope;
or B2 is OH and each of B1, B3-B8 is independently selected from the group of moieties denoted by K, provided that at least one of B1, B3-B8 is or contains a radioisotope;
or B1 and B3 are each OH and each of B2, B4-B8 is independently selected from the group of moieties denoted by K, provided that at least one of B4-B8 is or contains a radioisotope;
(c) coumarins having the formula (3)
where X and Y are, independently, O, S, or N—R1 (wherein R1 is H, alkyl, aryl, [11C]methyl, [18F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [124I]iodoalkyl, [124I]iodoaryl,] [125I]iodoalkyl, or [125I]iodoaryl);
and wherein
C3 is OH and each of C1-C2, C4-C6 is independently selected from the group of moieties denoted by K;
or
C4 is OH and each of C1-C3, C5-C6 is independently selected from the group of moieties denoted by K;
or
C5 is OH and each of C1-C4, C6 is independently selected from the group of moieties denoted by K;
or
C6 is OH and each of C1-C5 is independently selected from the group of moieties denoted by K;
or
C2 and C3═OH and each of C1, C4-C6 is independently selected from the group of moieties denoted by K;
or
C2 and C4═OH and each of C1, C3, C5-C6 is independently selected from the group of moieties denoted by K;
or
C2 and C5═OH and each of C1, C3-C4, C6 is independently selected from the group of moieties denoted by K;
or
C2 and C6═OH and each of C1, C3-C5 is independently selected from the group of moieties denoted by K;
or
C3 and C5═OH and each of C1-C2, C4, C6 is independently selected from the group of moieties denoted by K;
or
C4 and C6═OH and each of C1-C3, C5 is independently selected from the group of moieties denoted by K;
or
C2═C3═C5═OH and each of C1, C4, C6 is independently selected from the group of moieties denoted by K;
or
C2, C4 and C6═OH and each of C1, C3, C5 is independently selected from the group of moieties denoted by K;
wherein in each case at least one of C1-C6, X, or Y is or contains a radioisotope;
(d) flavones having the formula (4)
where X and Y are, independently, O, S, or N—R1 (wherein R1 is H, alkyl, aryl, [11C]methyl, [18F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [124]iodoalkyl, [124I]iodoaryl,] [125I]iodoalkyl, or [125I]iodoaryl);
and wherein
D3 is OH and each of D1-D2, D4-D6 is independently selected from the group of moieties denoted by K;
or
D4 is OH and each of D1-D3, D5-D6 is independently selected from the group of moieties denoted by K;
or
D5 is OH and each of D1-D4, D6 is independently selected from the group of moieties denoted by K;
or
D6 is OH and each of D1-D5 is independently selected from the group of moieties denoted by K;
or
D2 and D3 are OH and each of D1, D4-D6 is independently selected from the group of moieties denoted by K;
or
D2 and D4 are OH and each of D1, D3, D5-D6 is independently selected from the group of moieties denoted by K;
or
D2 and D5 are OH and each of D1, D3-D4, D6 is independently selected from the group of moieties denoted by K;
or
D2 and D6 are OH and each of D1, D3-D5 is independently selected from the group of moieties denoted by K;
or
D3 and D5 are OH and each of D1-D2, D4, D6 is independently selected from the group of moieties denoted by K;
or
D4 and D6 are OH and each of D1-D3, D5 is independently selected from the group of moieties denoted by K;
or
D2, D3 and D5 are OH, and D1, D4, D6 is independently selected from the group of moieties denoted by K;
or
D2, D4 and D6 are OH, and D1, D3, D5 is independently selected from the group of moieties denoted by K;
wherein in each case at least one of D1-D6, X, or Y is or contains a radioisotope;
(e) fused ring compounds having the formula (5)
where Z is O, S, N—R1 (wherein R1 is H, alkyl, aryl, [11C]methyl, [18F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [1241]iodoalkyl, [1241]iodoaryl,] [125I]iodoalkyl, or [125I]iodoaryl), CH2, or CH═CH;
and W is N or CH;
and wherein
E2 is OH and each of E1, E3-E5 is independently selected from the group of moieties denoted by K;
or
E3 is OH and each of E1-E2, E4-E5 is independently selected from the group of moieties denoted by K;
or
E4 is OH and each of E1-E3, E5 is independently selected from the group of moieties denoted by K;
or
E5 is OH and each of E1-E4 is independently selected from the group of moieties denoted by K;
or
E2 and E4 are OH and each of E1-E4 is independently selected from the group of moieties denoted by K;
or
E3 and E5 are OH and each of E1, E2, E4, is independently selected from the group of moieties denoted by K;
and wherein in each case at least one of E1-E5 or Z is or contains a radioisotope;
(e′) structurally related fused ring compounds in which E1 is a substituted aryl group, said compounds having the formula 5a:
where Z is O, S, N—R1 (wherein R1 is H, alkyl, aryl, [11C]methyl, [18F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [124I]iodoalkyl, [124I]iodoaryl,] [125I]iodoalkyl, or [125I]iodoaryl), CH2, or CH═CH;
W is N or CH;
and P is H, alkyl, aryl, [11C]methyl, 18F, [18F]fluoroalkyl, [18F]fluoroaryl, 123I, [123I]iodoalkyl, [123I]iodoaryl, 124I, [124I]iodoalkyl, [124I]iodoaryl,] 125I, [125I]iodoalkyl, or [125I]iodoaryl);
and wherein E2 is OH and each of E3-E5 is independently selected from the group of moieties denoted by K;
or
E3 is OH and each of E2, E4-E5 is independently selected from the group of moieties denoted by K;
or
E4 is OH and each of E2-E3, E5 is independently selected from the group of moieties denoted by K;
or
E5 is OH and each of E2-E4 is independently selected from the group of moieties denoted by K;
or
E2 and E4 are OH and each of E3, E5 is independently selected from the group of moieties denoted by K;
or
E3 and E5 are OH and each of E2, E4 is independently selected from the group of moieties denoted by K;
wherein in each case at least one of E1-E5, I′, or Z is or contains a radioisotope;
and wherein R′ is selected from the group consisting of H, NH—CH3, N(CH3)2 NH2, OCH3, NH—CO—CH3, F, I, CN, NO2, SO2—CH3, and radiolabeled isotopes thereof;
(f) imidazopyridines having the formula (6):
where F1-F5 are the same as E1-E5, and wherein at least one of F1-F5 is or contains a radioisotope;
or
(g) stilbenes having the formula (7):
where W1 and W2 are, independently, alkyl, aryl, or OH;
and wherein
G3 is OH and each of G1-G2, G4-G10 is independently selected from the group of moieties denoted by K;
or
G2 and G4 are OH and each of G1, G3, G5-G10 is independently selected from the group of moieties denoted by K;
or
G3 and G8 are OH and each of G1-G3, G4-G7, G9-G10 is independently selected from the group of moieties denoted by K;
or
G2=G4=G8═OH and each of G1, G3, G5-G7, G9-G10 is independently selected from the group of moieties denoted by K;
and wherein in each case at least one of G1-G10 is or contains a radioisotope;
and wherein, in each of compounds (a)-(g), K is selected from the group consisting of H;
alkyl;
aryl;
18F;
[18F]fluoroalkyl;
[18F]fluoroaryl;
123I;
[123I]iodoalkyl;
[123I]iodoaryl;
124I;
[124I]iodoalkyl;
[124I]iodoaryl;
125I;
[125I]iodoalkyl;
[125I]iodoaryl;
—SR1, or —NR1R2 (where R1 and R2 are independently H, alkyl, aryl, [11C]methyl, [18F]fluoroalkyl;
[18F]fluoroaryl;
[123I]iodoalkyl;
[123I]iodoaryl;
[124I]iodoalkyl;
[124I]iodoaryl;
[125I]iodoalkyl;
or [125I]iodoaryl);
—NO2;
—CN;
—S(═O)—R3 or —S(═O)2—R3 (where R3 is alkyl, aryl, [11C]methyl, [18F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [124I]iodoaryl, [125I]iodoalkyl, [125I]iodoaryl), or —OR4, —NR4R5, (wherein R4 and R5 are independently H, alkyl, aryl, [11C]methyl, [18F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [124]iodoalkyl, [124]iodoaryl, [125I]iodoalkyl, or [125I]iodoaryl));
and —OC(═O)—R6, —SC(═O)—R6, or —NH—C(═O)—R6 (where R6 is alkyl, aryl, [11C]methyl, [18F]fluoroalkyl, [18F]fluoroaryl, [123I]iodoalkyl, [123I]iodoaryl, [124I]iodoalkyl, [124I]iodoaryl, [125I]iodoalkyl, or [125I]iodoaryl).

137 more elements

Facts

Application

12/594,197Filed 31 Mar 2008 · us provisional application

Priority

30 Mar 2007

Published

US 2010/0135906 A13 Jun 2010

Granted

12 Feb 2013

Term ends

Not estimatedThe source records don’t support an estimate.

Classification9 codes

A61K 51/04
Characterised by the carrier , i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus: organic compounds
A61B 5/4088
Diagnosing or monitoring particular conditions of the nervous system: diagnosing of monitoring cognitive diseases, e.g. Alzheimer, prion diseases…
A61B 5/411
Detecting, measuring or recording for evaluating the immune or lymphatic systems: detecting or monitoring allergy or intolerance reactions to an…
A61K 31/57
Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids: substituted in position 17 beta by a chain…