Treatment of lung tumor colonies with 90Y targeted to blood vessels: comparison with the alpha-particle emitter 213Bi.
An in vivo lung tumor model system for radioimmunotherapy of lung metastases was used to test the relative effectiveness of the vascular- targeted beta-particle emitter 90Y, and alpha-particle emitter, 213Bi. Yttrium-90 was shown to be stably bound by CHXa" DTPA-MAb 201B conjugates and delivered efficiently to lung tumor blood vessels. Dosimetry calculations indicated that the lung received 16.2 Gy/MBq from treatment with 90Y MAb 201B, which was a sevenfold greater absorbed dose than any other organ examined. Therapy was optimal for 90Y with 3 MBq injected. Bismuth-213 MAb 201B also delivered a similar absorbed dose (15Gy/MBq) to the lung. Yttrium-90 was found to be slightly more effective against larger tumors than 213Bi, consistent with the larger range of 2 MeV beta particles from 90Y than the 8 MeV alpha particles from 213Bi. Treatment of EMT-6 tumors growing in immunodeficient SCID mice with 90Y or 213Bi MAb 201 resulted in significant destruction of tumor colonies; however, 90Y MAb 201B was toxic for the SCID mice, inflicting acute lung damage. In another tumor model, IC-12 rat tracheal carcinoma growing in SCID mouse lungs, 90Y therapy was more effective than 213Bi at destroying lung tumors. However, 90Y MAb 201B toxicity for the lung limited any therapeutic effect. We conclude that, although vascular-targeted 90Y MAb can be an effective therapeutic agent, particularly for larger tumors, in this model system, acute damage to the lung may limit its application.
Kennel
S J
SJ
Life Sciences Division, Oak Ridge National Laboratory, TN 37831-6101, USA. sj9@ornl.gov
Stabin
M
M
Yoriyaz
H
H
Brechbiel
M
M
Mirzadeh
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001729:Bismuth; D004307:Dose-Response Relationship, Radiation; D005260:Female; D017879:Isothiocyanates / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D004369:Pentetic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011868:Radioisotopes / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000009:adverse effects*; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D017879:Isothiocyanates; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; C085678:N-(2-amino-3-(4-isothiocyanatophenyl)propyl)cyclohexane-1,2-diamine-N,N',N',N'',N''-pentaacetic acid; D004369:Pentetic Acid; D001729:Bismuth