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

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 125I‐rhTIMP‐2 internalizes, which is an important feature for its possible use as a radiotherapeuticum if labelled with 131I. Labelling of rhTIMP‐2 was performed using the iodogen method resulting in a radiochemical yield of 51.1±11.8% (n=5) and a radiochemical purity of >98%. The trichloroacetic acid (TCA) precipitability of 123I rhTIMP‐2 was 95.2%. SDS‐PAGE confirmed the correct size (21 kDa) of the purified 123I rhTIMP‐2 without degradation. HPLC showed one radioactive peak with a retention time corresponding to the non‐labelled 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 123I rhTIMP‐2 as tumour‐imaging agent.