In vivo evaluation of In-111-DTPA-N-TIMP-2 in Kaposi sarcoma associated with HIV infection

Matrix metalloproteinases are the major agents responsible for the degradat ion of extracellular agents responsible for the degradation of extracellula r matrix and are produced at high levels by transformed and tumour cells, w here 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 demonstra ted that vascular invasion can be inhibited by inhibitors of matrix metallo proteinases. Imaging of visceral and cutaneous KS presents a problem and th erefore 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 In-111-DTPA-N-TIMP-2 were assessed in five patients with HIV infection and KS. Between 103.1 an d 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 b lood 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-ti me 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 t hree patients had no such problems. The tracer distributed predominantly to the kidneys and did not localise in other tissues. No KS lesions were clea rly identified. In-111-DTPA-N-TIMP-2 can be successfully prepared and admin istered to patients safely, with a biodistribution and dosimetry which woul d allow its use as an imaging tracer, It is unlikely to be of use for imagi ng KS, but may have a role in other tumours that produce matrix metalloprot einases.