Radioimaging applications of and novel formulations of teboroxime

Apparatus for performing cardiac imaging, comprising an imaging system, which comprises:

• 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;
• 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.

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:

• 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.

A method for cardiac imaging, comprising:

• 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—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.

Apparatus for performing cardiac imaging, comprising an imaging system, which comprises:

• 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;
• and
• is a boron derivative of the formula B—R3
• herein 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.

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—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.

A method for cardiac imaging, comprising performing a SPECT imaging procedure having a total imaging procedure duration of no more than 20 minutes, by:

• 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—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.