Kulasegaram, R. and Giersing, B.K. and Page, C.J. and Blower, P.J. and Williamson, R.A. and Peters, B.S. and O'Doherty, M.J. (2001) In Vivo Evaluation of 111In-DTPA-N-TIMP-2 in Kaposi Sarcoma Associated with HIV Infection. European Journal of Nuclear Medicine, 28 (6). pp. 756-761. ISSN 0340-6997.
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Matrix metalloproteinases are the major agents responsible for the degradation of extracellular matrix and are produced at high levels by transformed and tumour cells, where they participate in the metastatic process by allowing local invasion. They are also more active at sites of new normal growth and angiogenesis. In the early stages of Kaposi sarcoma (KS), in vitro studies have demonstrated that vascular invasion can be inhibited by inhibitors of matrix metalloproteinases. Imaging of visceral and cutaneous KS presents a problem and therefore the potential use of a labelled inhibitor of metalloproteinases, N-TIMP-2, with indium-111 was thought to present a possible imaging tool. The biokinetics, dosimetry and potential for imaging with 111In-DTPA-N-TIMP-2 were assessed in five patients with HIV infection and KS. Between 103.1 and 108.0 MBq of this agent was injected into each patient, and the dynamic uptake over the kidneys was assessed, whole body scans were performed and blood samples were obtained. The clearance from the blood was rapid, with a first component half-time of 16.6+/-3.4 min and a second component half-time of 9.68+/-2.68 h. Two out of five patients experienced minor shivering but one of these patients was generally unwell before the study. The last three patients had no such problems. The tracer distributed predominantly to the kidneys and did not localise in other tissues. No KS lesions were clearly identified. 111In-DTPA-N-TIMP-2 can be successfully prepared and administered to patients safely, with a biodistribution and dosimetry which would allow its use as an imaging tracer. It is unlikely to be of use for imaging KS, but may have a role in other tumours that produce matrix metalloproteinases.
|Additional information:||0340-6997 (Print) Clinical Trial Journal Article|
|Uncontrolled keywords:||Adult HIV Infections/*complications Humans Male Middle Aged Pentetic Acid/analogs & derivatives/diagnostic use Radiopharmaceuticals/chemical synthesis/*diagnostic use/pharmacokinetics Sarcoma, Kaposi/etiology/*radionuclide imaging Tissue Distribution Tissue Inhibitor of Metalloproteinase-2/diagnostic use Whole-Body Counting|
|Divisions:||Faculties > Science Technology and Medical Studies > School of Biosciences > Protein Science Group|
|Depositing User:||Richard Williamson|
|Date Deposited:||30 Sep 2008 18:31|
|Last Modified:||08 Jun 2012 15:09|
|Resource URI:||http://kar.kent.ac.uk/id/eprint/5309 (The current URI for this page, for reference purposes)|
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