Synthesis, quality control and in vivo evaluation of [123I] rhTIMP-2, a potential tumour-imaging agent

✍ Scribed by Ruth Oltenfreiter; Ingrid Burvenich; Ludovicus Staelens; Annabelle Lejeune; Francis Frankenne; Jean-Michel Foidart; Guido Slegers

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: French
• Weight: 151 KB
• Volume: 48
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.937

✦ Synopsis

Matrix metalloproteinases (MMPs) are enzymes involved in the turnover of the extracellular matrix. Their overexpression in tumours may provide a target for diagnostic imaging by using labelled MMP inhibitors. MMPs are inhibited by endogenous tissue inhibitors of metalloproteinases (TIMPs). The enhanced production of MT1-MMP, located on the surface of cells within or in the direct vicinity of the tumour, and the high affinity interaction between TIMP-2 and MT1-MMP suggested that TIMP-2 could be a potential agent for non-invasive monitoring of cancer MMP levels, diagnosis of primary and secondary tumours and tumour response to MMP inhibitor therapy. There is also evidence that 125 I-rhTIMP-2 internalizes, which is an important feature for its possible use as a radiotherapeuticum if labelled with 131 I. Labelling of rhTIMP-2 was performed using the iodogen method resulting in a radiochemical yield of 51.1 AE 11.8% (n=5) and a radiochemical purity of >98%. The trichloroacetic acid (TCA) precipitability of 123 I rhTIMP-2 was 95.2%. SDS-PAGE confirmed the correct size (21 kDa) of the purified 123 I rhTIMP-2 without degradation. HPLC showed one radioactive peak with a retention time corresponding to the nonlabelled rhTIMP-2. In vivo biodistribution showed no long-term accumulation in organs and the possibility to accumulate in the tumour. These results show the potential of 123 I rhTIMP-2 as tumour-imaging agent.