Biodistribution of gadolinium incorporated in lipid emulsions intraperitoneally administered for neutron-capture therapy with tumor-bearing hamsters

Emulsions containing a distearylamide (Gd-DTPA-SA) or a distearylester (Gd- DTPA-SE) of Gd (gadolinium)-diethylenetriaminepentaacetic acid (Gd-DTPA) we re intraperitoneally injected in Greene's melanoma-bearing hamsters at a do se of 2.0 mi (3.0 or 6.0 mg Gd) per hamster. In the standard-Gd and high-Gd formulations used, the weight ratios of soybean oil, water, Gd-DTPA deriva tive (Gd-DTPA-SA or Gd-DTPA-SE), hydrogenated L-alpha-phosphatidylcholine f rom egg yolk (HEPC) and co-surfactant (HCO-60, Myrj 53, Myrj 59 or Brij 700 ) were 7.36:92:1 :2:3 and 7.36:92 :2: 1 :3, respectively, When the effects of the co-surfactants on the biodistribution of Cd from Gd-DTPA-SA-containi ng emulsions in the standard-Gd formulation were compared, the HCO-60 emuls ion exhibited the highest Gd accumulation in tumors, possibly resulting fro m its fast and complete absorption, its small particle size (78 nm) and the stable coat on the particle surfaces with polyoxyethylene, Brij 700 emulsi on kept the highest blood Gd concentration for a prolonged period, possibly due to particle properties similar to those of HCO-60, However, it exhibit ed a slower Gd accumulation in tumors, only reaching an identical level, in comparison with the HCO-60 emulsion. This suggested the tumor to be satura ted with lipid particles. When Gd-DTPA-SE was used instead of Gd-DTPA-SA, i ts HCO-60 emulsion exhibited only very poor Gd-accumulation due to its easy degradation. The HCO-60 emulsion particles containing Gd-DTPA-SA in the hi gh-Gd formulation (6.0 mg Gd in 2 mi) exhibited irt,vivo behavior identical to those in the standard-Gd formulation; then the Gd level in tumors reach ed 107 mu g Gd/g tumor (wet), and the tumor: blood (T/B) and tumor: skin (T /Sk) Gd concentration ratios were 13.2 and 5.6, respectively, at 48 h after intraperitoneal administration. These results suggest that when intraperit oneally administered, this HCO-60 emulsion, and possibly also the correspon ding BI ij 700 emulsion, may be an excellent delivery system for accumulati ng Gd in tumors in neutron-capture therapy (NCT).