Biodistribution studies of anti-Thy 1.2 IgM immunoconjugates: implications for radioimmunotherapy.
We have prepared 111In radioimmunoconjugates (RICs) of the IgM isotype with specificity for the murine T cell/neuroectodermal surface antigen, Thy 1.2. Using gamma camera immunoscintigraphy, we have analyzed the biodistribution patterns of the RICs after intravenous and intraperitoneal injection into normal Thy 1.2+ and Thy 1.2- mice. Both routes of administration show antigen-specific uptake by the splenic T lymphocyte population. A high degree of nonspecific uptake by the reticuloendothelial system is also observed. Analysis of the specific activity of various segments of spleens from RIC-injected animals shows inhomogeneous uptake of the RIC not readily apparent by immunoscintigraphy. Animals injected with the RIC and then given high dose total body irradiation showed rapid shifts in radionuclide distribution away from the target cell population and into the general reticuloendothelial system, suggesting that death of the target cell can alter RIC biodistribution. Analyses of RIC biodistribution patterns will contribute to optimization of treatment by radioimmunotherapy.
Macklis
R M
RM
Joint Center for Radiation Therapy, Dana-Farber Cancer Institute, Boston, MA 02115.
Kaplan
W D
WD
Ferrara
J L
JL
Kinsey
B M
BM
Kassis
A I
AI
Burakoff
S J
SJ
D000818:Animals; D007075:Immunoglobulin M / Q000493:pharmacokinetics*; D007205:Indium Radioisotopes; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007518:Isoantibodies / Q000493:pharmacokinetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D014018:Tissue Distribution
D007075:Immunoglobulin M; D007205:Indium Radioisotopes; D007518:Isoantibodies; C035678:anti-Thy antibody