Tissue dosimetry of liposome-radionuclide complexes for internal radiotherapy: toward liposome-targeted therapeutic radiopharmaceuticals.
BACKGROUND
Quantitative examination of the important physical parameters, such as the tumor absorbed dose and the tumor-to-normal-tissue (T-NT) absorbed dose ratios, for effective use of radionuclide-liposome conjugates m internal radiotherapy was carried out.


METHODS
The Medical Internal Radiation Dose (MIRD) formalism was used to develop a set of dosimetric equations. Pharmacokinetic functions used as input information to the dosimetric model were derived from experimental time-biodistribution data. Multilamellar (MLV), small unilamellar (SUV) and sterically stabilized (GM1- and PEG-coated) liposomes were examined in combination with the very promising particle emitting radionuclides: 67Cu, 188Re and 211At. For comparative purposes, the widely used: 90Y and 131I were also included in the study. For all radionuclide-liposome combinations, the mean absorbed dose per amount of radioactivity administered was obtained: (i) for two different types of human xenografts located in the muscle and liver tissue, and (ii) for normal liver, spleen, kidneys, and total body.


RESULTS
Regardless of radionuclide, the poorest values were obtained for the MLV liposomes. Due to more rapid uptake of sterically stabilized (GM,-coated) liposomes to the muscle tumor tissue as compared to SUVs, 211At and 188Re deliver higher tumor doses when combined with the former, while 67Cu, 90Y and 131I are more effective with SUVs. The most promising results were obtained for the [211At-GM1] complex in the liver tumor.


CONCLUSIONS
The importance of liposome size and steric barrier when designing effective radionuclide-carrier systems was revealed, but most importantly the optimal matching between the radionuclide half-life and the time of maximum liposome accumulation ratio between the tumor and normal tissue.
Kostarelos
K
K
Weill Medical College of Cornell University-New York Presbyterian Hospital, NY 10021, USA. kok2001@med.cornell.edu
Emfietzoglou
D
D
D000818:Animals; D001246:Astatine / Q000627:therapeutic use*; D003301:Copper Radioisotopes / Q000627:therapeutic use*; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008081:Liposomes; D008113:Liver Neoplasms / Q000532:radiotherapy; D051379:Mice; D019042:Muscle Neoplasms / Q000532:radiotherapy; D019275:Radiopharmaceuticals; D012211:Rhenium / Q000627:therapeutic use*; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
D003301:Copper Radioisotopes; D007457:Iodine Radioisotopes; D008081:Liposomes; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; D012211:Rhenium; D001246:Astatine