RADIOIMAGING APPLICATIONS OF AND NOVEL FORMULATIONS OF TEBOROXIME
First Claim
Patent Images
1. A method for cardiac imaging, comprising:
- administering to an adult human subject an amount of a 99mTc-containing species having a radioactivity of less than 5 mCi at a time of administration; and
performing a SPECT imaging procedure of a cardiac region of interest (ROI) of the subject, wherein said 99mTc-containing species has the formula 99mTcX(Y)3Z, wherein;
X is an anion;
each Y, which is independently chosen, is a vicinal dioxime having the formula HON═
C(R1)C(R2)═
NOH or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are each independently hydrogen, halogen, alkyl, aryl, amino or a 5 or 6-membered nitrogen or oxygen containing heterocycle, or together R1 and R2 are —
(CR8CR9)—
wherein n is 3, 4, 5 or 6 and R8 and R9 are each independently hydrogen or alkyl; and
Z is a boron derivative of the formula B—
R3 wherein R3 is hydroxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, carboxyalkyl, carboxyalkenyl, hydroxyalkyl, hydroxyalkenyl, alkoxyalkyl, alkoxyalkenyl, haloalkyl, haloalkenyl, aryl, arylalkyl or (R4R5N)-alkyl and R4 and R5 are each independently hydrogen, alkyl, or arylalkyl, or R4 and R5 when taken together with the nitrogen atom to which they are attached form a 5 or 6-membered nitrogen containing heterocycle.
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Abstract
A method for cardiac imaging is provided, including administering to an adult human subject an amount of a teboroxime species having a radioactivity of less than 5 mCi at a time of administration, and performing a SPECT imaging procedure of a cardiac region of interest (ROI) of the subject. Other embodiments are also described.
155 Citations
293 Claims
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1. A method for cardiac imaging, comprising:
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administering to an adult human subject an amount of a 99mTc-containing species having a radioactivity of less than 5 mCi at a time of administration; and performing a SPECT imaging procedure of a cardiac region of interest (ROI) of the subject, wherein said 99mTc-containing species has the formula 99mTcX(Y)3Z, wherein; X is an anion; each Y, which is independently chosen, is a vicinal dioxime having the formula HON═
C(R1)C(R2)═
NOH or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are each independently hydrogen, halogen, alkyl, aryl, amino or a 5 or 6-membered nitrogen or oxygen containing heterocycle, or together R1 and R2 are —
(CR8CR9)—
wherein n is 3, 4, 5 or 6 and R8 and R9 are each independently hydrogen or alkyl; andZ is a boron derivative of the formula B—
R3wherein R3 is hydroxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, carboxyalkyl, carboxyalkenyl, hydroxyalkyl, hydroxyalkenyl, alkoxyalkyl, alkoxyalkenyl, haloalkyl, haloalkenyl, aryl, arylalkyl or (R4R5N)-alkyl and R4 and R5 are each independently hydrogen, alkyl, or arylalkyl, or R4 and R5 when taken together with the nitrogen atom to which they are attached form a 5 or 6-membered nitrogen containing heterocycle. - View Dependent Claims (2, 3, 32, 33, 35, 36, 45, 49, 50, 51, 52, 55, 60)
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4-31. -31. (canceled)
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34. (canceled)
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37-44. -44. (canceled)
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71. Apparatus for performing cardiac imaging, comprising an imaging system, which comprises:
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SPECT imaging functionality; and a control unit configured to drive the imaging functionality to perform a SPECT imaging procedure on a cardiac region of interest (ROI) of an adult human subject after administration to the subject of a 99mTc-containing species having a radioactivity of less than 5 mCi at a time of administration, wherein said 99mTc-containing species has the formula 99mTcX(Y)3Z, wherein; X is an anion; each Y, which is independently chosen, is a vicinal dioxime having the formula HON═
C(R1)C(R2)═
NOH or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are each independently hydrogen, halogen, alkyl, aryl, amino or a 5 or 6-membered nitrogen or oxygen containing heterocycle, or together R1 and R2 are —
(CR8CR9)—
wherein n is 3, 4, 5 or 6 and R8 and R9 are each independently hydrogen or alkyl; andZ is a boron derivative of the formula B—
R3wherein R3 is hydroxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, carboxyalkyl, carboxyalkenyl, hydroxyalkyl, hydroxyalkenyl, alkoxyalkyl, alkoxyalkenyl, haloalkyl, haloalkenyl, aryl, arylalkyl or (R4R5N)-alkyl and R4 and R5 are each independently hydrogen, alkyl, or arylalkyl, or R4 and R5 when taken together with the nitrogen atom to which they are attached form a 5 or 6-membered nitrogen containing heterocycle. - View Dependent Claims (73, 75, 76)
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72. (canceled)
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74. (canceled)
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77-97. -97. (canceled)
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98. Apparatus for cardiac imaging, comprising a portable computer-communicatable data carrier, which is configured to contain imaging protocol information for performing SPECT imaging on an adult human subject, the protocol information including an indication to administer a 99mTc-containing species of the formula 99mTcX(Y)3Z, wherein:
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X is an anion; each Y, which is independently chosen, is a vicinal dioxime having the formula HON═
C(R1)C(R2)═
NOH or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are each independently hydrogen, halogen, alkyl, aryl, amino or a 5 or 6-membered nitrogen or oxygen containing heterocycle, or together R1 and R2 are —
(CR8CR9)—wherein n is 3, 4, 5 or 6 and R8 and R9 are each independently hydrogen or alkyl; and Z is a boron derivative of the formula B—
R3wherein R3 is hydroxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, carboxyalkyl, carboxyalkenyl, hydroxyalkyl, hydroxyalkenyl, alkoxyalkyl, alkoxyalkenyl, haloalkyl, haloalkenyl, aryl, arylalkyl or (R4R5N)-alkyl and R4 and R5 are each independently hydrogen, alkyl, or arylalkyl, or R4 and R5 when taken together with the nitrogen atom to which they are attached form a 5 or 6-membered nitrogen containing heterocycle. - View Dependent Claims (100, 101, 104)
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99. (canceled)
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102-103. -103. (canceled)
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105-198. -198. (canceled)
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199. A method for cardiac imaging, comprising:
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administering to an adult human subject a 99mTc-containing species having a radioactivity of less than 50 mCi at a time of the administering; and performing a SPECT imaging procedure on a cardiac region of interest (ROI) of the subject with a image acquisition period having a duration not exceeding 5 minutes, wherein said 99mTc-containing species has the formula 99mTcX(Y)3Z, wherein; X is an anion; each Y, which is independently chosen, is a vicinal dioxime having the formula HON═
C(R1)C(R2)═
NOH or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are each independently hydrogen, halogen, alkyl, aryl, amino or a 5 or 6-membered nitrogen or oxygen containing heterocycle, or together R1 and R2 are —
(CR8CR9)—wherein n is 3, 4, 5 or 6 and R8 and R9 are each independently hydrogen or alkyl; and Z is a boron derivative of the formula B—
R3wherein R3 is hydroxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, carboxyalkyl, carboxyalkenyl, hydroxyalkyl, hydroxyalkenyl, alkoxyalkyl, alkoxyalkenyl, haloalkyl, haloalkenyl, aryl, arylalkyl or (R4R5N)-alkyl and R4 and R5 are each independently hydrogen, alkyl, or arylalkyl, or R4 and R5 when taken together with the nitrogen atom to which they are attached form a 5 or 6-membered nitrogen containing heterocycle. - View Dependent Claims (200, 202, 204, 207, 208, 212, 213, 214, 216, 231, 232, 233, 234, 235, 236, 237, 240, 241, 247, 250, 251, 252)
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201. (canceled)
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259. Apparatus for performing cardiac imaging, comprising an imaging system, which comprises:
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PECT imaging functionality; and control unit configured to drive the imaging functionality to perform a SPECT imaging procedure on a cardiac region of interest (ROI) of an adult human subject after administration to the subject of a 99mTc-containing species having a radioactivity of less than 50 mCi at a time of the administration, wherein the imaging procedure has a image acquisition period having a duration not exceeding 5 minutes, and wherein said 99mTc-containing species has the formula 99mTcX(Y)3Z, wherein; is an anion; each Y, which is independently chosen, is a vicinal dioxime having the formula HON═
C(R1)C(R2)═
NOH or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are each independently hydrogen, halogen, alkyl, aryl, amino or a 5 or 6-membered nitrogen or oxygen containing heterocycle, or together R1 and R2 are —
(CR8CR9)—
wherein n is 3, 4, 5 or 6 and R8 and R9 are each independently hydrogen or alkyl; andis a boron derivative of the formula B—
R3herein R3 is hydroxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, carboxyalkyl, carboxyalkenyl, hydroxyalkyl, hydroxyalkenyl, alkoxyalkyl, alkoxyalkenyl, haloalkyl, haloalkenyl, aryl, arylalkyl or (R4R5N)-alkyl and R4 and R5 are each independently hydrogen, alkyl, or arylalkyl, or R4 and R5 when taken together with the nitrogen atom to which they are attached form a 5 or 6-membered nitrogen containing heterocycle. - View Dependent Claims (260, 268, 269)
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261-267. -267. (canceled)
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270-275. -275. (canceled)
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276. A method for cardiac imaging, comprising:
- subjecting an adult human subject to stress;
during the stress, administering to the subject a 99mTc-containing species having a radioactivity of between 20 and 40 mCi at a time of the administering; and performing a SPECT stress imaging procedure on a cardiac region of interest (ROI) of the subject, with an image acquisition period having a duration not exceeding 5 minutes; and during the stress image acquisition period, acquiring a number of photons greater than or equal to at least one of the following numbers; one in 5000 photons emitted from the ROI during the stress image acquisition period, and 200,000 photons emitted from a portion of the ROI, which portion has a volume of no more than 500 cc, wherein said 99mTc-containing species has the formula 99mTcX(Y)3Z, wherein; X is an anion; each Y, which is independently chosen, is a vicinal dioxime having the formula HON═
C(R1)C(R2)═
NOH or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are each independently hydrogen, halogen, alkyl, aryl, amino or a 5 or 6-membered nitrogen or oxygen containing heterocycle, or together R1 and R2 are (CR8CR9)—wherein n is 3, 4, 5 or 6 and R8 and R9 are each independently hydrogen or alkyl; and Z is a boron derivative of the formula B—
R3wherein R3 is hydroxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, carboxyalkyl, carboxyalkenyl, hydroxyalkyl, hydroxyalkenyl, alkoxyalkyl, alkoxyalkenyl, haloalkyl, haloalkenyl, aryl, arylalkyl or (R4R5N)-alkyl and R4 and R5 are each independently hydrogen, alkyl, or arylalkyl, or R4 and R5 when taken together with the nitrogen atom to which they are attached form a 5 or 6-membered nitrogen containing heterocycle. - View Dependent Claims (289)
- subjecting an adult human subject to stress;
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277-288. -288. (canceled)
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292. A method for cardiac imaging, comprising performing a SPECT imaging procedure having a total imaging procedure duration of no more than 20 minutes, by:
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performing first and second administrations of first and second radiopharmaceutical agents to a subject, respectively, wherein at least one of the first and second radiopharmaceutical agents includes a 99mTc-containing species, performing, during a rest image acquisition period, rest SPECT imaging on a cardiac region of interest (ROI) of the subject, performing, during a stress image acquisition period, stress SPECT imaging on the ROI, and during each of the rest and stress image acquisition periods, acquiring a number of photons greater than or equal to at least one of the following numbers; one in 5000 photons emitted from the ROI during the image acquisition period, and 200,000 photons emitted from a portion of the ROI, which portion has a volume of no more than 500 cc, wherein said 99mTc-containing species has the formula 99mTcX(Y)3Z, wherein;
X is an anion;each Y, which is independently chosen, is a vicinal dioxime having the formula HON═
C(R1)C(R2)═
NOH or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are each independently hydrogen, halogen, alkyl, aryl, amino or a 5 or 6-membered nitrogen or oxygen containing heterocycle, or together R1 and R2 are —
(CR8CR9)—
wherein n is 3, 4, 5 or 6 and R8 and R9 are each independently hydrogen or alkyl; and
Z is a boron derivative of the formula B—
R3wherein R3 is hydroxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, carboxyalkyl, carboxyalkenyl, hydroxyalkyl, hydroxyalkenyl, alkoxyalkyl, alkoxyalkenyl, haloalkyl, haloalkenyl, aryl, arylalkyl or (R4R5N)-alkyl and R4 and R5 are each independently hydrogen, alkyl, or arylalkyl, or R4 and R5 when taken together with the nitrogen atom to which they are attached form a 5 or 6-membered nitrogen containing heterocycle.
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293-333. -333. (canceled)
Specification