Imaging tumor folate receptors using ¹¹¹In-DTPA-methotrexate

It is known that membrane folic acid receptors are responsible for cellular accumulation of folate and folate analogs, such as methotrexate, and overexpressed on various tumor cells. This study was aimed to develop an ¹¹¹In labelled DTPA-methotrexate (DTPA-MTX) to image tumor folate receptors in vivo. DTPA-MTX was synthesized by reacting ethylenediamine with MTX. The resulting amino analogue of MTX was reacted with DTPA dianhydride in basic aqueous solution followed by dialysis. Tissue distribution was determined in breast tumor-bearing rats at 0.5, 2, 24, and 48 h (n=3/time interval). To determine receptor-mediated process ¹¹¹In-DTPA-MTX was co- administered with varying blocking doses of cold folate to tumor-bearing rats. Planar imaging and whole-body autoradiograms were performed. The data was compared to that using ¹¹¹In-DTPA. In animal studies, tumor/blood count ratios at 0.5-48 h gradually increased from 0.8±0.32 to 2.2±0.41 with ¹¹¹In-DTPA-MTX. Conversely, these values showed time-dependent decrease from 1.19±0.69 to 0.56±0.10 with ¹¹¹In-DTPA in the same time period. Tumor/muscle and tumor/blood count density ratios significantly decreased with high doses of folic acid co-administration. Planar images and autoradiograms confirmed that the tumors could be visualized acceptably with ¹¹¹In-DTPA-MTX. The results indicate the feasibility of using ¹¹¹In- DTPA-MTX to image tumors through a folate receptor-mediated process.