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Synthesis, quality control and in vivo evaluation of [ 123 I] rhTIMP‐2, a potential tumour‐imaging agent
Author(s) -
Oltenfreiter Ruth,
Burvenich Ingrid,
Staelens Ludovicus,
Lejeune Annabelle,
Frankenne Francis,
Foidart JeanMichel,
Slegers Guido
Publication year - 2005
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.937
Subject(s) - chemistry , biodistribution , matrix metalloproteinase , in vivo , trichloroacetic acid , enzyme , extracellular matrix , imaging agent , matrix (chemical analysis) , in vitro , biochemistry , chromatography , microbiology and biotechnology , biology
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±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 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 123 I rhTIMP‐2 as tumour‐imaging agent. Copyright © 2005 John Wiley & Sons, Ltd.