Radiolabeled Matrix Metalloproteinase Inhibitors for Breast Cancer Therapy

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  • Radiolabeled Matrix Metalloproteinase Inhibitors for Breast Cancer Therapy Book Detail

  • Author :
  • Release Date : 2002
  • Publisher :
  • Genre :
  • Pages : 12
  • ISBN 13 :
  • File Size : 7,7 MB
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Radiolabeled Matrix Metalloproteinase Inhibitors for Breast Cancer Therapy by PDF Summary

Book Description: Matrix Metalloproteinases (MMPs), a family of over 20 types of enzymes, collectively are capable of degrading all the components of the extracellular matrix. MMP-2 and MMP-9 (also known as gelatinases) are specifically thought to play critical roles in tumor cell invasion and are frequently co-expressed in breast cancer. Cyclic peptides containing the sequence HWGF have been described as selective inhibitors of MMP-2 and MMP-9. We tested the hypothesis that gelatinase expression may provide a target for in vivo tumor imaging using a radiolabeled gelatinase inhibitor. The peptide, DOTA-CTTHWGFTLC (DOTA-CTT), was labeled with Cu-64 T 1/2 1/2% = l2.7 h.%, which has a decay scheme suitable for both PET imaging and cancer therapy. This conjugate maintained MMP-2 inhibitory activity comparable to %Ilomastat, a broad-range inhibitor of MMPs. An increase in the MMP-2/9 activity of human metastatic breast cancer MDA-MB-435 tumors in nude mice was observed from 4 to 10 weeks post-implantation. MicroPET images of Cu-64-DOTA-CTT in the tumor-bearing nude mice showed tumor uptake at 8-wk post-implantation; however, the same mouse with 5-wk palpable tumors showed no uptake of the tracer, suggesting that the MMP-2 and MMP-9 activity is related to the stage of tumor growth. These data suggest the potential of radiolabeled gelatinase inhibitors as markers for imaging the metastatic capability of human breast cancer.

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