In order to assess whether 131-I-or 90-Y- LL2 will be best for RIT, the applicant proposes to conduct 2 separate Phase I therapy trials, one with 131-I-LL2 and the other with 90-Y-LL2. The escalation of radioimmunotherapeutic doses of 131-I or 90- Y-LL2 will be guided by bone marrow dosimetry. Most importantly, each patient will have two targeting studies, one with 131-I-LL2 IgG and the other with 111-In-LL2 (as surrogate 90-Y distribution) so that the tumor and red marrow dosimetry with each agent can be compared directly in the same patient. However, since the applicant is not certain if equal radiation doses to the red marrow will result in comparable toxicity for both isotopes, due to the higher retention of Y90 in the bone with potentially increased toxicity, the maximum tolerated dose (MTD) to the red marrow will be first determined for 90-Y or 131-I-LL2. Once the MTD to red marrow has been determined, tumor doses delivered with each agent at its extrapolated MTD will be compared directly in the same patient. Data from the applicant's laboratory have shown very similar retention (expressed as percent ID/g) of In-111 and 90-Y-LL2 in lymphoma tumors. Moreover, the 90-Y radiation dose to tumor predicted by In-111-LL2 was nearly identical to that predicted by Y-88-LL2. Thus the applicant will determine if there is a therapeutic advantage of 90-Y-LL2 IgG compared to 131- I-LL2 IgG based on data from 30-36 patients who received both In-111 and 131- I-LL2 dosimetric doses prior to therapy.
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