Synthesis and evaluation of BPA-Gd-DTPA complex as an MRI contrast agent and as a carrier for neutron capture therapy

Takahashi, Kazunori*; Nakamura, Hiroyuki*; Furumoto, Shozo*; Yamamoto, Kazuyoshi ; Matsumura, Akira*; Fukuda, Hiroshi*; Yamamoto, Yoshinori*

We synthesized a BPA-Gd-DTPA compound, as a carrier for neutron capture therapy to be used for MRI contrast media. Pinanediol was used as the protective group for B(OH)2 group of BPA, and the BPA unit was connected to the DTPA framework through an amide bond. The biodistribution studies were performed after injection of the compound into AH109A hepatoma bearing Donryu rats. The concentrations of Gd and boron were measured by prompt g-ray analyses. The tumor uptakes (% ID/g) were 1% and 0.3% at 20 min and 60 min after injection, respectively and were higher than that of carborane-Gd-DTPA, which we previously reported. However, liver and kidney uptake was very high and tumor/blood ratio was very low (0.38) compared to that of BPA itself (ca. 3.0). Alfa autoradiogram of a tumor bearing rat showed higher concentration of boron in the tumor compared to surrounding muscle and very high in the intestine. Although tumor selectivity of the compound was higher than that of carborane-Gd-DTPA, further studies of the synthesis and in vivo evaluation of better binary compounds are continuing.