Targeted radiolabeled compounds and their use for the treatment and diagnosis of cancer

A method of diagnosing a patient for the presence of a tumor, said tumor comprising cancer cells characterized by at least one of butyrylcholinesterase expression and androgen binding affinity, said method comprising administering to said patient an effective amount for diagnostic imaging of a compound of the formula:

• wherein Ra represents OH or:
• X represents H, F, Cl, or a C1-C8 alkyl, or C1-C8 alkoxy group;
• Y represents H, C1-C8 alkyl, C5-C14 aryl, or a C5-C14 aryloxy group;
• Z represents H, C1-C8 alkyl, C5-C14 aryl, or a C5-C14 aryloxy group;
• R represents halogen, radiohalogen, or a C1-C8 alkyl, C5-C14 aryl, C1-C8 alkylthio, C1-C8 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, C3-C12 cycloalkyl, or Sn(C1-C4 alkyl)3 group;
• Rb represents halogen, radiohalogen, or a C1-C6 alkoxy or C1-C8 alkanoate group, an androgen receptor binding ligand linked to the said compound via a cleavable linking moiety, or:
• any of said alkyl, alkenyl, alkynyl, alkylthio, alkoxy and cycloalkyl group being optionally substituted by at least one halogen, OH, SH, NH2, C1-C4 monoalkylamino, C1-C4 dialkylamino, COOH, CN, NO2, C1-C4 alkyl, C1-C4 alkoxy or phenyl group, any of said aryl, aryloxy, and phenyl group being optionally substituted by at least one halogen, OH, SH, NH2, C1-C4 monoalkylamino, C1-C4 dialkylamino, COOH, CN, NO2, C1-C4 alkyl or C1-C4 alkoxy group;
• said radiohalogen represents 123I, 124I, 125I, 131I, 211At, 18F, 76Br, 77Br, or 80mBr;
• stereoisomeric forms and pharmaceutically acceptable salts of said at least one compound;
• with the proviso that at least one of the Ra and Rb substitutents represents:
• the wavy line indicating the point of attachment to the ribose moiety;
• and
• performing imaging to diagnose the presence of said tumor.

A method for monitoring tumor activity in a subject, said method comprising administering an effective amount for diagnostic imaging of a compound of the formula:

• wherein Ra represents OH or:
• X represents H, F, Cl, or a C1-C8 alkyl, or C1-C8 alkoxy group;
• Y represents H, C1-C8 alkyl, C5-C14 aryl, or a C5-C14 aryloxy group;
• Z represents H, C1-C8 alkyl, C5-C14 aryl, or a C5-C14 aryloxy group;
• R represents halogen, radiohalogen, or a C1-C8 alkyl, C5-C14 aryl, C1-C8 alkylthio, C1-C8 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, C3-C12 cycloalkyl, or Sn(C1-C4 alkyl)3 group;
• Rb represents halogen, radiohalogen, or a C1-C6 alkoxy or C1-C8 alkanoate group, an androgen receptor binding ligand linked to the said compound via a cleavable linking moiety, or:
• any of said alkyl, alkenyl, alkynyl, alkylthio, alkoxy and cycloalkyl group being optionally substituted by at least one halogen, OH, SH, NH2, C1-C4 monoalkylamino, C1-C4 dialkylamino, COOH, CN, NO2, C1-C4 alkyl, C1-C4 alkoxy or phenyl group, any of said aryl, aryloxy, and phenyl group being optionally substituted by at least one halogen, OH, SH, NH2, C1-C4 monoalkylamino, C1-C4 dialkylamino, COOH, CN, NO2, C1-C4 alkyl or C1-C4 alkoxy group;
• said radiohalogen represents 123I, 124I, 125I, 131I, 211At, 18F, 76Br, 77Br, or 80mBr;
• stereoisomeric forms and pharmaceutically acceptable salts of said at least one compound;
• with the proviso that at least one of the Ra and Rb substitutents represents:
• the wavy line indicating the point of attachment to the ribose moiety;
• obtaining an image of said tumor to establish a baseline tumor size in said subject;
• readministering said compound to said subject;
• and
• obtaining at least one other image of said tumor producing a result which is indicative of the tumor activity in said patient.

A compound of the formula:

• wherein X represents H, F, Cl, or a C1-C4 alkyl, or C1-C4 alkoxy group;
• Y represents H or a C1-C4 alkyl group;
• Z represents H or a C1-C4 alkyl group;
• R represents halogen, radiohalogen, or a C1-C4 alkyl, C6-C14 aryl, C1-C8 alkylthio, C1-C8 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, C3-C12 cycloalkyl, or Sn(C1-C4 alkyl)3 group;
• any of said alkyl, alkenyl, alkynyl, alkylthio, alkoxy, and cycloalkyl group being optionally substituted by at least one halogen, OH, SH, NH2, C1-C4 monoalkylamino, C1-C4 dialkylamino, COOH, CN, NO2, C1-C4 alkyl, C1-C4 alkoxy or phenyl group, any of said aryl and phenyl group being optionally substituted by at least one halogen, OH, SH, NH2, C1-C4 monoalkylamino, C1-C4 dialkylamino, COOH, CN, NO2, C1-C4 alkyl or C1-C4 alkoxy group;
• L is a cleavable bifunctional linking moiety;
• and said radiohalogen represents 123I, 124I, 125I, 131I, 211At, 18F, 76Br, 77Br, or 80mBr;
• and stereoisomeric forms and pharmaceutically acceptable salts of said compound.