Radiosynthesis and evaluation of [11C]SU11274 for in vivo PET imaging of MET receptors

Objectives To radiosynthesize and evaluate a molecular imaging probe, termed [11C]SU11274 ([11C]14), for quantification of MET receptors in human cancers in vivo.

Methods (3-[3,5-dimethyl-4-(4-methyl-piperazine-carbonyl)-1H-pyrrol-2-ylmethylene]-2-oxo-2,3-dihydro-1H-indole-5-sulfonic acid (3-chlorophenyl)-methyl amide (14) was radiolabelled with C-11 through radiomethylation of 3-[3,5-dimethyl-4-(piperazine-1-carbonyl)-1H-pyrrol-2-ylmethylene]-2-oxo-2,3-dihyro-1H-indole-5-sulfonic acid (3-chlorophenyl)-methyl amide hydrochloride (13) that was designed as the precursor. For in vivo microPET studies, two human lung cancer xenograft models were established using MET-positive NCI-H1975 and MET- negative NCI-H520. MRI (9.4T) studies were performed right after microPET to co-register with microPET images. In vitro histological studies were further conducted after microPET and MRI imaging.

Results The synthesis of 13 was achieved in 10 steps with a total yield of 9.7%. [11C]14 was obtained in a range of 5-10 % radiochemical yield and over 95% radiochemical purity after HPLC preparation. Quantitative microPET study showed that the tumor uptake of the [11C]14 in the NCI-H1975 xenograft was significantly higher than that in the NCI-H520 xenograft, which is consistent with their corresponding immunohistochemical tissue staining patterns of MET receptors from the same animals.

Conclusions These studies demonstrated that [11C]14-PET is an appropriate imaging marker for quantification of MET receptor in vivo and can facilitate efficacy evaluation in the clinical development of MET targeted cancer therapeutics