RADIOIMAGING MOIETIES COUPLED TO PEPTIDEASE-BINDING MOIETIES FOR IMAGING TISSUES AND ORGANS THAT EXPRESS PEPTIDASES
First Claim
1. A compound comprising a peptidase-binding moiety conjugated to a radiopharmaceutical moiety or an optical imaging moiety.
6 Assignments
0 Petitions
Accused Products
Abstract
Conjugates, methods and kits are described for imaging tissues and organs that express one or more peptidases. In a preferred embodiment of the invention, a series of di-(2-pyridylmethyl)amine (D) ligands, which can bind M(CO)3+ [M=Tc or Re], were coupled to lisinopril (L). Aliphatic tethers with varying number of methylene groups (3, 4, 5, and 7; D(C4)L, D(C5)L, D(C6)L, and D(C8)L, respectively) were utilized, with in vitro inhibitory activity increasing with increasing number of methylene groups. The D(C8)L conjugate was observed to be significantly more potent than D(C4)L. In vivo specificity for ACE was studied in both tissue distribution and gamma imaging studies, demonstrating localization in tissues with high ACE content. Localization was blocked by pretreatment with lisinopril.
8 Citations
43 Claims
- 1. A compound comprising a peptidase-binding moiety conjugated to a radiopharmaceutical moiety or an optical imaging moiety.
- 14. A method of imaging one or more organs or tissues or both of a mammal comprising administering to a mammal an effective amount of a compound comprising a peptidase-binding moiety conjugated to a radio-imaging moiety or an optical imaging moiety and obtaining an image of one or more organs or tissues or both of the mammal.
-
24. A kit comprising:
- (i) compound comprising a peptidase-binding moiety conjugated to a metal chelating moiety, and (ii) radionuclide.
- View Dependent Claims (25)
-
26. A method of staging a pathological condition associated with one or more organs or tissues or both of a mammal comprising:
- (i) administering to a mammal an effective amount of a compound comprising a peptidase-binding moiety conjugated to a radio-imaging moiety, (ii) obtaining an image of the one or more organs or tissues or both of said mammal;
(iii) determining from said image the amount of peptidase which is present in the one or more organs or tissues or both of said mammal, and (iv) utilizing the amount determined and a control amount to arrive at a stage of the pathological condition. - View Dependent Claims (27, 29, 30)
- (i) administering to a mammal an effective amount of a compound comprising a peptidase-binding moiety conjugated to a radio-imaging moiety, (ii) obtaining an image of the one or more organs or tissues or both of said mammal;
- 28. A method of monitoring a mammal'"'"'s response to therapy for a pathological condition associated with one or more organs or tissues or both of the mammal comprising (i) administering to a mammal an effective amount of a compound comprising a peptidase-binding moiety conjugated to a radio-imaging moiety, (ii) obtaining an image of the one or more organs or tissues or both of the mammal, (iii) determining from said image the amount of peptidase which is present in the one or more organs or tissues or both of the mammal, and (iv) utilizing the amount determined and a control amount to gauge the mammal'"'"'s response, if any, to a therapy.
-
33. A method of quantifying expression of a peptidase in one or more organs or tissues or both of a mammal comprising administering to a mammal an effective amount of a compound including a peptidase-binding moiety conjugated to a radio-imaging moiety, obtaining an image of the one or more organs or tissues or both of the mammal;
- quantifying from the image and a series of standard images an amount of expression of the peptidase in the one or more organs or tissues or both of the mammal.
- 34. A method of subjecting a mammal in need thereof to radiotherapeutic treatment comprising administering to a mammal an effective amount of a compound comprising a peptidase-binding moiety conjugated to a radiotherapeutic moiety.
-
37. A compound of the following formula:
-
(PBM)n-(LIN)-(CHE)mwherein PBM comprises a peptidase binding moiety, n is 1, 2 or 3, LIN is a covalent bond, —
CH2—
, —
NH—
, or a linear or branched chain that is 2-20 carbon atoms in length, and optionally bonded to or within the chain are 1-6 heteroatoms including amino, oxygen, sulfur, carbonyl, urea, or amide, aromatic rings, cyclic aliphatic rings, heteroaromatic rings, or heterocyclic aliphatic rings, and which covalently links the one or more PBMs with the one or more CHEs;CHE comprises a chelating moiety that can be a monodentate, bidentate or polydentate ligand capable of binding a radionuclide and m is 1, 2 or 3. - View Dependent Claims (38, 39, 40, 41, 42, 43)
-
Specification