Radioimmunotherapy for the intensification of conditioning before stem cell transplantation: Differences in dosimetry and biokinetics of Re-188- and Tc-99m-labeled anti-NCA-95 MAbs

A new concept is the intensification of preparative regimens for patients w ith advanced leukemia using monoclonal antibodies (MAbs) with an affinity f or beta emitter-labeled bone marrow. Re-188 is a high-energy beta emitter t hat has therapeutic promise. Our first aim was to clarify whether the thera peutic application of Re-188-MAb against nonspecific cross-reacting antigen 95 (NCA-95) can be predicted from biokinetic data derived from Tc-99m-labe led NCA-95. Our second aim was to show that a radiation absorbed dose of gr eater than or equal to 12 Gy in the bone marrow can be achieved using Re-18 8-MAb. Methods: Dosimetric data were obtained for both radiotracers from mu ltiple planar whole-body scans (double-head gamma camera), blood samples, a nd urine measurements from 12 patients with advanced leukemia. Radiation ab sorbed doses were calculated using MIRDOSE 3 software. Results: Radiation a bsorbed doses to bone marrow, liver, spleen, lung, and kidney were 2,24, 0. 50, 1.93, 0.05, and 0.90 mGy/MBq, respectively, using Tc-99m-MAb and 1.45, 0.43, 1.32, 0.07, and 0.71 mGy/MBq, respectively, using Re-188-MAb, These d ifferences were statistically significant for bone marrow, spleen, and kidn ey. The main differences were less accumulation of Re-188-MAb in bone marro w (31% +/- 13% compared with 52% +/- 13%) and faster elimination through ur ine (25% +/- 3% compared with 15% +/- 5% after 24 h). On the basis of these data, a mean marrow dose of 14 +/- 7 Gy was achieved in 12 patients suffer ing from leukemia after application of approximately 10 +/- 2 GBq Re-188-MA b. Conclusion: Myeloablative radiation absorbed doses can easily be achieve d using Re-188-MAb. Tc-99m- and Re-188-MAb showed similar whole-body distri butions. However, direct prediction of radiation absorbed doses from the (T C)-T-99m-MAb, assuming identical biokinetic behavior, is not valid for the Re-188-MAb in a single patient. Therefore, individual dosimetry using Re-18 8-MAb is needed to calculate therapeutic activity.