Treatment of lung tumor colonies with 90Y targeted to blood vessels:: Comparison with the α-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 Y-90, and alpha-particle emitter, Bi-213. 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 Y-90 MAb 201B, which was 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 delivered 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 with 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, inflicting acute lung damage. In another tumor model, IC-12 rat tracheal carcinoma 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 limited any therapeutic effect. We conclude that, although vascular-targeted Y-90 MAb can be an effective therapeutic agent, particularly for larger tumors, in this model system, acute damage to the lung may limit its application. NUCL MED BIOL 26;1:149-157, 1999. (C) 1998 Elsevier Science Inc.