Technetium -99m complex for examining the renal function

• US 4,925,650 A
• Filed: 11/16/1988
• Issued: 05/15/1990
• Est. Priority Date: 11/16/1988
• Status: Expired due to Term

• Current Assignee: Mallinckrodt Medical Inc. (Mallinckrodt plc)
• Original Assignee: Mallinckrodt Incorporated (Mallinckrodt plc)
• Inventors: Nosco, Dennis L., Verbruggen, Alfons M.
• Primary Examiner(s): Maples, John S.
• Application Number:
  US07/272,177
• Time in Patent Office: 545 Days
• Field of Search: 424/1.1, 534/14
• US Class Current: 424/1.65
• CPC Class Codes: A61K 2123/00 Preparations for testing in vivo
• CPC Class Codes: A61K 51/0478 complexes from non-cyclic ligands, e.g. EDTA, MAG3
• CPC Class Codes: C07F 13/005 Compounds without a metal-carbon linkage

Abstract

The invention relates to a technetium-99m complex of the general formula ##STR1## wherein Z is a sulphur atom or an amino group of the general formula R₁₇ --N--(R₁₈)_k, in which k is 0 or 1 and R₁₇ and R₁₈ have the same meanings as the symbols R₁ -R₁₆ ;

each of the symbols R₁ -R₁₆ is individually selected from the group consisting of hydrogen, straight or branched, unsubstituted or substituted alkyl having 1-4 carbon atoms, and ACOOH, wherein A is a straight or branched, unsubstituted or substituted alkly group having 0-4 carbon atoms;

and R₅ together with R₆ or R₉ together with R₁₀ additionally may form an oxygen atom;

Tc represents technetium-99m;

t is 0 or 1; and

n is 0 or 1;

with the provisos that

(a) if R₁₅, R₁₆, R₁₇ and/or R₁₈ are/is ACOOH, A is a straight or branched, unsubstituted or substituted alkyl group having 1-4 carbon atoms;

(b) at least one of the symbols R₁ -R₁₈ is ACOOH; and

(c) if t is 1, at least two of the symbols R₁ -R₁₈ are ACOOH;

or a pharmaceutically acceptable salt of this compound.

The invention further relates to a radiopharmaceutical composition comprising said complex, to the use of this composition for examining the renal function, and to a kit for preparing such a composition.

Claims

1. Technetium-99m complex of the general formula ##STR6## wherein Z is an amino group of the general formula R₁₇ --N--(R₁₈)_k, in which k is 0 or 1 and R₁₇ and R₁₈ have the same meanings as the symbols R₁ -R₁₆ is individually selected from the group consisting of hydrogen, straight or branched, unsubstituted or substituted alkyl having 1-4 carbon atoms, and ACOOH, wherein A is a straight or branched, unsubstituted or substituted alkyl group having 0-4 carbon atoms;

and R₅ together with R₆ or R₉ together with R₁₀ additionally may form an oxygen atom;

Tc represents technetium-99m;

t is 0 or 1; and

n is 0 or 1;

with the provisos that

(a) if at least one of R₁₅, R₁₆, R₁₇ and R₁₈ is ACOOH, A is a straight or branched, unsubstituted or substituted alkyl group having 1-4 carbon atoms;

(b) at least one of the symbols R₁ -R₁₈ is ACOOH; and

(c) if t is 1, at least two of the symbols R₁ -R₁₈ are ACOOH;

or a pharmaceutically acceptable salt of this compound.

2. A complex as claimed in claim 1 of the general formula ##STR7## wherein Z is an amino group of the general formula R₁₇ '"'"'--N--(R₁₈ '"'"')_k, in which k is 0 or 1 and R₁₇ '"'"' and R₁₈ '"'"' have the same meanings as the symbols R₁ '"'"', R₃ '"'"', R₅ '"'"', R₉ '"'"', R₁₁ '"'"', R₁₃ '"'"', R₁₅ '"'"' and R₁₆ '"'"',

each of the symbols R₁ '"'"', R₃ '"'"', R₅ '"'"', R₉ '"'"', R₁₁ '"'"', R₁₃ '"'"', R₁₅ '"'"' and R₁₆ '"'"' is individually selected from the group consisting of hydrogen, methyl and (CH₂)_q COOH, wherein q is 0 or 1,

Tc represents technetium-99m, and

t is 0 or 1,

with the provisos that

(a) if at least one of R₁₅ '"'"' and R₁₆ '"'"' is (CH₂)_q COOH, q is 1

(b) at least one of the symbols R₁ '"'"', R₃ '"'"', R₅ '"'"', R₉ '"'"', R₁₁ '"'"', R₁₃ '"'"', R₁₅ and R₁₆ '"'"' is (CH₂)_q COOH,

(c) at most four of the symbols R₁ '"'"', R₃ '"'"', R₅ '"'"', R₉ '"'"', R₁₁ '"'"', R₁₃ '"'"', R₁₅ '"'"' and R₁₆ '"'"' are (CH₂)_q COOH, and

(d) if t is 1, at least two of the symbols R₁ '"'"', R₃ '"'"', R₅ '"'"', R₉ '"'"', R₁₁ '"'"', R₁₃ '"'"', R₁₅ '"'"' and R₁₆ '"'"' are (CH₂)_q COOH,

or a pharmaceutically acceptable salt of this compound.

3. A radiopharmaceutical composition for examining the renal function which, in addition to a liquid, pharmaceutically acceptable carrier material, comprises a technetium-99m complex, characterized in that the composition comprises a complex as claimed in claim 1 or 2 as the technetium-99m complex.

4. A method of performing a renal function examination, characterized in that a composition as claimed in claim 3 is administered to a warm-blooded living being in a quantity of 0.1 to 30 mCi, per 70 kg of body weight, and the radioactive radiation emitted by the living being is then recorded.

5. A method according to claim 4, wherein the quantity of the composition administered is 0.5 to 10 mCi per 70 kg of body weight.

6. Technetium-99m complex of the general formula ##STR8## wherein Z is a sulphur atom or an amino group of the general formula R₁₇ --N--(R₁₈)_k,

in which K is 0 or 1 and R₁₇ and R₁₈ have the same meanings as the symbols R₁ -R₁₆ ;

each of the symbols R₁ -R₁₆ is individually selected from the group consisting of hydrogen, straight or branched, unsubstituted or substituted alkyl having 1-4 carbon atoms, and ACOOH, wherein A is a straight or branched, unsubstituted or substituted alkyl group having 0-4 carbon atoms;

and R₅ together with R₆ or R₉ together with R₁₀ additionally may form an oxygen atom;

Tc represents technetium-99m;

t is 0 or 1;

n is 0 or 1;

with the proviso that

at least two of the symbols R₁ -R₁₈ are ACOOH, wherein A is a straight or branched unsubstituted or substituted alkyl group having 1-4 carbon atoms,

or a pharmaceutically acceptable salt of this compound.

7. A complex as claimed in claim 6, of the general formula ##STR9## wherein each of the symbols R₁ '"'"', R₃ '"'"', R₅ '"'"', R₉ '"'"' R₁₁ '"'"', R₁₃ '"'"', R₁₅ '"'"' and R₁₆ '"'"'is individually selected from the group consisting of hydrogen, methyl and (CH₂)_q COOH, wherein q is 0 or 1,

Tc represents technetium-99m, and

t is 0 or 1,

with the provisos that

(a) at least two of the symbols R₁ '"'"', R₃ '"'"', R₅ '"'"', R₉ '"'"', R₁₁, R₁₃ '"'"', R₁₅ '"'"' and R₁₆ '"'"' are (CH₂)_q COOH, wherein q is 1, and

(b) at most four of the symbols R₁ '"'"', R₃ '"'"', R₅ '"'"', R₉ '"'"', R₁₁ '"'"', R₁₃ '"'"', R₁₅ '"'"' and R₁₆ '"'"' are (CH₂)_q COOH,

or a pharmaceutically acceptable salt of this compound.

8. A radiopharmaceutical composition for examining the renal function which, in addition to a liquid, pharmaceutically acceptable carrier material, comprises a technetium-99m complex, characterized in that the composition comprises a complex as claimed in claim 6 or 7 as the technetium-99m complex.

9. A method of performing a renal function examination, characterized in that a composition as claimed in claim 8 is administered to a warm-blooded living being in a quantity of 0.1 to 30 mCi per 70 kg of body weight, and the radioactive radiation emitted by the living being is then recorded.

10. A method according to claim 9, wherein the quantity of the composition administered is 0.5 to 10 mCi per 70 kg of body weight.

11. Technetium-99m complex of the general formula ##STR10## wherein Z is a sulphur atom or an amino group of the general formula R₁₇ --N--(R₁₈)_k,

in which k is 0 or 1 and R₁₇ and R₁₈ have the same meanings as the symbols R₁ -R₁₆ ;

each of the symbols R₁ -R₁₆ is individually selected from the group consisting of hydrogen, straight or branched, unsubstituted or substituted alkyl having 1-4 carbon atoms, and COOH;

and R₅ together with R₆ or R₉ together with R₁₀ additionally may form an oxygen atom;

Tc represents technetium-99m;

t is 0 or 1; and

n is 0 or 1;

with the provisos that

(a) at least one of the symbols R₁ -R₁₈ is COOH; and

(b) if t is 1, at least two of the symbols R₁ -R₁₈ are COOH,

or a pharmaceutically acceptable salt of this compound.

12. A complex as claimed in claim 11 of the general formula ##STR11## wherein each of the symbols R₁ '"'"', R₃ '"'"', R₅ '"'"', R₉ '"'"', R₁₁, R₁₃ '"'"', R₁₅ '"'"' and R₁₆ '"'"' is individually selected from the group consisting of hydrogen, methyl and COOH,

Tc represents technetium-99m;

t is 0 or 1; and

n is 0 or 1;

with the provisos that

(a) at least one of the symbols R₁ '"'"', R₃ '"'"', R₅ '"'"', R₉ '"'"', R₁₁ '"'"', R₁₃ '"'"', R₁₅ '"'"' and R₁₆ '"'"' is COOH,

(b) at most four of the symbols R₁ '"'"', R₃ '"'"', R₅ '"'"' R₉ '"'"', R₁₁ '"'"', R₁₃, R₁₅ '"'"' and R₁₆ '"'"' are COOH, and

(c) if t is 1, at least two of the symbols R₁ '"'"', R₃ '"'"', are COOH,

or a pharmaceutically acceptable salt of this compound.

13. A radiopharmaceutical composition for examining the renal function which, in addition to a liquid, pharmaceutically acceptable carrier material, comprises a technetium-99m complex, characterized in that the composition comprises a complex as claimed in claim 11 or 12 as the technetium-99m complex.

14. A method of performing a renal function examination, characterized in that a composition as claimed in claim 13 is administered to a warm-blooded living being in a quantity of 0.1 to 30 mCi per 70 kg of body weight, and the radioactive radiation emitted by the living being is then recorded.

15. A method according to claim 14, wherein the quantity of the composition administered is 0.5 to 10 mCi per 70 kg of body weight.