Preparation and evaluation of para-[211At]astatobenzoyl labeled anti-renal cell carcinoma antibody A6H F(ab')2. In vivo distribution comparison with para-[125I]iodobenzoyl labeled A6H F(ab')2.
A preliminary investigation of an 211At labeled anti-renal cell carcinoma antibody fragment, A6H F(ab')2, was conducted. In the investigation, A6H F(ab')2 was labeled by conjugation with N-succinimidyl p-[211At]astatobenzoate, and the in vivo biodistribution was evaluated in athymic mice bearing TK-82 renal cell carcinoma xenografts. As a control, p-[125I]iodobenzoyl labeled A6H F(ab')2 was coinjected with the astatinated F(ab')2. The data obtained demonstrated that the two radiolabels (211At and 125I) had quite similar distributions, providing evidence that the 211At remained attached to the A6H F(ab')2 in vivo. Further, the astatinated antibody attained a 2:1 tumor-to-blood ratio, and greater than 35:1 tumor-to-muscle ratio, at 4h post-injection, suggesting that this antibody conjugate could be used to evaluate treatment of metastatic renal cell carcinoma in a mouse model.
Wilbur
D S
DS
Department of Radiation Oncology, University of Washington, Seattle 98195.
Vessella
R L
RL
Stray
J E
JE
Goffe
D K
DK
Blouke
K A
KA
Atcher
R W
RW
D000818:Animals; D001246:Astatine / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000378:metabolism* / Q000532:radiotherapy*; D004195:Disease Models, Animal; D004355:Drug Stability; D005069:Evaluation Studies as Topic; D007128:Immunoglobulin Fragments / Q000378:metabolism; D000922:Immunotoxins / Q000378:metabolism* / Q000627:therapeutic use; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D007553:Isotope Labeling / Q000379:methods; D007680:Kidney Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000532:radiotherapy*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D007128:Immunoglobulin Fragments; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D001246:Astatine