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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Jörg Kotzerke - , Universität Ulm (Autor:in)
  • Gerhard Glatting - (Autor:in)
  • Ulrike Seitz - (Autor:in)
  • Marion Rentschier - (Autor:in)
  • Bernd Neumaier - (Autor:in)
  • Donald Bunjes - (Autor:in)
  • Christian Duncker - (Autor:in)
  • Dagmar Dohr - (Autor:in)
  • Lothar Bergmann - (Autor:in)
  • Sven N. Reske - (Autor:in)

Abstract

A new concept is the intensification of preparative regimens for patients with advanced leukemia using monoclonal antibodies (MAbs) with an affinity for β emitter-labeled bone marrow. 188Re is a high-energy β emitter that has therapeutic promise. Our first aim was to clarify whether the therapeutic application of 188Re-MAb against nonspecific cross- reacting antigen 95 (NCA-95) can be predicted from biokinetic data derived from 99mTc-labeled NCA-95. Our second aim was to show that a radiation absorbed dose of ≥12 Gy in the bone marrow can be achieved using 188Re- MAb. Methods: Dosimetric data were obtained for both radiotracers from multiple planar whole-body scans (double-head γ camera), blood samples, and urine measurements from 12 patients with advanced leukemia. Radiation absorbed doses were calculated using MIRDOSE 3 software. Results: Radiation absorbed 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 99mTc-MAb and 1.45, 0.43, 1.32, 0.07, and 0.71 mGy/MBq, respectively, using 188Re-MAb. These differences were statistically significant for bone marrow, spleen, and kidney. The main differences were less accumulation of 188RE-MAb in bone marrow (31% ± 13% compared with 52% ± 13%) and faster elimination through urine (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 suffering from leukemia after application of approximately 10 ± 2 GBq 188Re-MAb. Conclusion: Myeloablative radiation absorbed doses can easily be achieved using 188Re-MAb. 99mTc- and 188Re-MAb showed similar whole-body distributions. However, direct prediction of radiation absorbed doses from the 99mTc-MAb, assuming identical biokinetic behavior, is not valid for the 188Re-MAb in a single patient. Therefore, individual dosimetry using 188Re-MAb is needed to calculate therapeutic activity.

Details

OriginalspracheEnglisch
Seiten (von - bis)531-537
Seitenumfang7
FachzeitschriftJournal of Nuclear Medicine
Jahrgang41
Ausgabenummer3
PublikationsstatusVeröffentlicht - März 2000
Peer-Review-StatusJa
Extern publiziertJa

Externe IDs

PubMed 10716329

Schlagworte

Schlagwörter

  • Re, Bone marrow transplantation, Dosimetry, Monoclonal antibody against nonspecific cross-reacting antigen 95, Radioimmunotherapy