CONTRAST AGENTS FOR MYOCARDIAL PERFUSION IMAGING

1 . A contrast agent comprising an imaging moiety and a compound selected from an annonaceous acetogenin, a quinone acetogenin, a substituted chromone, and an open-chain deguelin analog.

2 . The contrast agent of claim 1 of formula (I)

wherein

m is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14;

n is 0, 1, 2, 3, 4, 5, 6, 7, or 8;

o is 0 or 1;

p is 5, 6, 7, 8, 9, 10, 11, or 12;

--- is absent or a single bond;

when --- is absent, A and B are independently selected from hydrogen and an imaging moiety;

when --- is a single bond, A and B are each (C(R 1 ) 2 ) k ;

k is 1 or 2, provided that when A and B are each (C(R 1 ) 2 ) k , one k is 1 and the other is 1 or 2;

R 1 , R 2 , R 4 , R 5 , R 7 , R 8 , R 10 , R 15 , and R 16 are independently at each occurrence hydrogen, hydroxy, or an imaging moiety;

R 3 is hydrogen, hydroxy, or an imaging moiety;

R 3′ is hydrogen; or

R 3 and R 3′ , together with the carbon atom to which they are attached, form C═O or C═CR 13 R 14 ;

R 6 is hydrogen, hydroxy, or an imaging moiety;

R 6′ is hydrogen; or

R 6 and R 6′ , together with the carbon atom to which they are attached, form C═O or C═CR 13 R 14 ;

R 9 is hydrogen, hydroxy, or an imaging moiety;

R 9′ is hydrogen; or

R 9 and R 9′ , together with the carbon atom to which they are attached, form C═O or C═CR 13 R 14 ;

R 11 is C 1 -C 6 alkyl; and

R 12 , R 13 , and R 14 , are independently hydrogen, C 1 -C 6 alkyl optionally substituted with an imaging moiety, arylalkyl, or an imaging moiety;

provided that at least one imaging moiety is present in formula (I).

3 . The contrast agent of claim 2 wherein R 4 is an imaging moiety.

4 . The contrast agent of claim 2 wherein R 5 is an imaging moiety.

5 . The contrast agent of claim 2 wherein R 8 is an imaging moiety.

6 . The contrast agent of claim 2 wherein R 9 is an imaging moiety.

7 - 10 . (canceled)

11 . The contrast agent of claim 1 of formula (II)

wherein

q is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14;

r is 0, 1, 2, 3, 4, 5, 6, 7, or 8;

s is 0 or 1;

t is 5, 6, 7, 8, 9, 10, 11, or 12;

--- is absent or a single bond;

when --- is absent, D and E are independently selected from hydrogen and an imaging moiety;

when --- is a single bond, D and E are each (C(R 15 ) 2 ) u ;

u is 1 or 2, provided that when D and E are each (C(R 15 ) 2 ) u , one u is 1 and the other is 1 or 2;

R 15 , R 16 , R 18 , R 19 , R 21 , and R 22 , are independently at each occurrence hydrogen, hydroxy, or an imaging moiety;

R 17 is hydrogen, hydroxy, or an imaging moiety;

R 17′ is hydrogen; or

R 17 and R 17′ , together with the carbon atom to which they are attached, form C═O or C═CR 27 R 28 ;

R 20 is hydrogen, hydroxy, or an imaging moiety;

R 20′ is hydrogen; or

R 20 and R 20′ , together with the carbon atom to which they are attached, form C═O or C═CR 27 R 28 ;

R 23 is hydrogen, hydroxy, or an imaging moiety;

R 23′ is hydrogen; or

R 23 and R 23′ , together with the carbon atom to which they are attached, form C═O or C═CR 27 R 28 ;

R 24 , R 25 , and R 26 are independently hydrogen, C 1 -C 6 alkyl optionally substituted with an imaging moiety, C 1 -C 6 alkoxy, hydroxy, halo, or an imaging moiety; and

R 27 and R 28 are independently hydrogen, C 1 -C 6 alkyl optionally substituted with an imaging moiety, arylalkyl, an imaging moiety;

provided that at least one imaging moiety is present in formula (II).

12 . The contrast agent of claim 11 wherein R 18 , R 19 , R 22 , or R 23 is an imaging moiety.

13 . The contrast agent of claim 11 wherein R 22 is an imaging moiety.

14 . (canceled)

15 . The contrast agent of claim 1 of formula (III)

wherein

G is —S—, —O—,

J is S, C(R 37 ) 2 , or O;

is a single or double bond; and

R 30 , R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , R 37 , R 38 , R 39 , R 40 , R 41 , and R 42 are independently at each occurrence hydrogen, C 1 -C 6 alkyl optionally substituted with an imaging moiety, C 1 -C 6 alkoxy optionally substituted with an imaging moiety, or an imaging moiety; provided that when is a double bond, R 31 and R 32 are absent; and

provided at least one imaging moiety is present in formula (III).

16 - 21 . (canceled)

22 . The contrast agent of claim 1 of formula (IV)

wherein

n, m, and o are independently 1, 2, 3, or 4;

Z is O, S, or NR 46 ;

R 45 is an imaging moiety or C 1 -C 4 alkyl optionally substituted with an imaging moiety;

R 46 is hydrogen or C 1 -C 3 alkyl;

Ar is phenyl, furyl, thienyl, oxazolinyl, isoxazolinyl, thiazolyl, isothiazolyl, pyridyl, naphthyl, pyrimidinyl, or pyrazinyl;

G is absent or O; and

L is an imaging moiety;

provided that when G is absent, o is 3.

23 - 24 . (canceled)

25 . The contrast agent of claim 1 wherein the imaging moiety is a radioisotope for nuclear medicine imaging, a paramagnetic species for use in MRI imaging, an echogenic entity for use in ultrasound imaging, a fluorescent entity for use in fluorescence imaging, or a light-active entity for use in optical imaging.

26 . The contrast agent of claim 25 wherein the paramagnetic species for use in MRI imaging is Gd 3+ , Fe 3+ , In 3+ , or Mn 2+ .

27 . The contrast agent of claim 25 wherein the echogenic entity for use in ultrasound imaging is a fluorocarbon encapsulated surfactant microsphere.

28 . The contrast agent of claim 25 wherein the radioisotope for nuclear medicine imaging is 11 C, 13 N, 18 F, 123 I, 124 I, 125 I, 99m Tc, 95 Tc, 111 In, 76 Br, 62 Cu, 64 Cu, 67 Ga, or 68 Ga.

29 . The contrast agent of claim 28 wherein the imaging moiety is 18 F.

30 . The contrast agent of claim 28 wherein the imaging moiety is 99m Tc.

31 . A method of imaging myocardial perfusion comprising administering to a patient a contrast agent which comprises an imaging moiety and a compound selected from an annonaceous acetogenin, a quinone acetogenin, a substituted chromone and an open-chain deguelin analog; and scanning the patient using diagnostic imaging.

32 . The method of claim 31 wherein the imaging moiety is a radioisotope for nuclear medicine imaging, a paramagnetic species for use in MRI imaging, an echogenic entity for use in ultrasound imaging, a fluorescent entity for use in fluorescence imaging, or a light-active entity for use in optical imaging.