Labelled adrenomedullin derivatives and their use for imaging and therapy

摘要

The present invention relates to an adrenomedullin derivative including an adrenomedullin peptide, or a fragment thereof chelated or otherwise bound to at least one active agent. Examples of active agents include a paramagnetic element, a radioactive element and a fibrinolytic agent, among others. Paramagnetic agents have a distribution that is relatively easily shown through Magnetic Resonance Imaging (MRI). Radioactive agents have applications in imaging and delivery of radiations, depending on the specific element included in the active agent. Delivery of fibrinolytic agents mainly to a specific organ, such as for example to the lungs, allows to substantially improve the specificity and efficacy of thrombolytic therapy by allowing local delivery of the fibrinolytic agent, thereby reducing the risks of major bleeding in the therapy of the organ. If the organ is the lungs, a non-limiting example of pathology treatable with the fibrinolytic agent is pulmonary embolus.

主权项

1. A method of determining the presence and density of adrenomedullin receptor-bearing cells in a mammal comprising:
administering to the mammal an effective amount of labelled adrenomedullin derivative to achieve binding between the labelled adrenomedullin derivative and adrenomedullin-receptor-bearing cells; and imaging the mammal to determine distribution of the labelled adrenomedullin derivative; the labelled adrenomedullin derivative comprising an adrenomedullin fragment having the sequence: X1-X2-X3-X4-Thr-Val-Gln-Lys-Leu-Ala-His-Gln-Ile-Tyr-Gln-Phe-Thr-Asp-Lys-Asp-Lys-Asp-Asn-Val-Ala-Pro-Arg-Ser-Lys-Ile-Ser-Pro-Gln-Gly-Tyr (SEQ ID NO:3), wherein:
X1 is absent or is selected from the group consisting of: Tyr-Arg-Gln-Ser-Met-Asn-Asn-Phe-Gln-Gly-Leu-Arg-Ser-Phe-Gly, Ser-Phe-Gly and Gly-Gly-Ala-Gly;X2 is Cys or HomoCys;when X1 is Ser-Phe-Gly or Gly-Gly-Ala-Gly, X3 is Arg-Phe-Gly-Thr or a linear or branched PEG moiety having at least two Poly(ethylene glycol) (PEG) subunits;when X1 is absent or Tyr-Arg-Gln-Ser-Met-Asn-Asn-Phe-Gln-Gly-Leu-Arg-Ser-Phe-Gly, X3 is a linear or branched PEG moiety having at least two Poly(ethylene glycol) (PEG) subunits; andX4 is Cys or HomoCys.