In vivo PET tumour imaging using an [F-18] labelled aptamer targeting tenascin-C

Objectives Tenascin-C is an extracellular matrix adhesion modulating protein, highly expressed in the microenvironment of numerous solid tumors. High tenascin-C expression reduces the prognosis of disease-free survival in patients with several cancers. Previous human studies displayed significant uptake of [Tc-99m]TTA1, a tenascin-C targeting aptamer, in a variety of solid tumours such as lung, breast and brain malignancies

Methods Here we labelled TTA1 with fluorine-18 for PET imaging using 1-[3-(2-[¹⁸F]-fluoropyridin-3-yloxy)propyl]pyrrole-2,5-dione. Whole body biodistributions and pharmacokinetics of [¹⁸F]TTA1 were evaluated in Wistar rats and in nu/nu mice bearing U251 human glioblastoma tumors

Results In both species, the main routes of body elimination of [¹⁸F]TTA1 were the urinary tract and the hepato enteric route. Blood radioactivity, derived from heart time activity curves, demonstrated vascular persistence of this aptamer with a half life of elimination of 20 min in rats. Tumoral uptake was rapid with a maximum observed 15 min after injection, corresponding to 1.7 +/- 0.6 % of ID/cc, and decreasing to 0.9 +/- 0.4 % at 90 min. In comparison, muscular uptake reached 0.7 +/- 0.2 % of ID/cc at 15 min and 0.17 +/- 0.06 % of ID/cc at 90 min post injection, yielding a tumor-to-muscle ratio of 2.3 and 5.4 at 15 and 90 min, respectively

Conclusions This first application of an aptamer for PET imaging is encouraging and may open the possibility of in vivo tumoral characterisation of tenascin-C in solid tumors

Research Support Supported by EMIL (European Molecular Imaging Laboratories) EU contract LSH-2004-503569