Treatment of lung tumor colonies with Y-90 targeted to blood vessels: Comparison with the alpha-particle emitter Bi-213

An in vivo lung tumor model system for radioimmunotherapy of lung metastase s was used to test the relative effectiveness of the vascular-targeted beta -particle emitter Y-90, and alpha-particle emitter, Bi-213. Yttrium-90 was shown to be stably bound by CHXa" DTPA-MAb 201B conjugates and delivered ef ficiently to lung tumor blood vessels. Dosimetry calculations indicated tha t the lung received 16.2 Gy/MBq from treatment with Y-90 MAb 201B, which wa s a sevenfold greater absorbed dose than any other organ examined. Therapy was optimal for Y-90 with 3 MBq injected. Bismuth-213 MAb 201B also deliver ed a similar absorbed dose (15Gy/MBq) to the lung. Yttrium-90 was found to be slightly more effective against larger tumors than Bi-213, consistent wi th the larger range of 2 MeV beta particles from Y-90 than the 8 MeV alpha particles from Bi-213. Treatment of EMT-6 tumors growing in immunodeficient SCID mice with Y-90 or Bi-213 MAb 201 resulted in significant destruction of tumor colonies; however, Y-90 MAb 201B was toxic for the SCID mice, infl icting acute lung damage. In another tumor model, IC-12 rat tracheal carcin oma growing in SCID mouse lungs, Y-90 therapy was more effective than 213Bi at destroying lung tumors. However, Y-90 MAb 201B toxicity for the lung li mited any therapeutic effect. We conclude that, although vascular-targeted Y-90 MAb can be an effective therapeutic agent, particularly for larger tum ors, in this model system, acute damage to the lung may limit its applicati on. NUCL MED BIOL 26;1:149-157, 1999. (C) 1998 Elsevier Science Inc.