Dosimetry with 188Re-labelled monoclonal anti-CD66 antibodies

 

 Buy Article Permissions and Reprints

Summary

Aim: For the therapeutic application of radiopharmaceuticals the activity is determined on an individual basis. Here we investigated the accuracy for a simplified assessment of the residence times for a ¹⁸⁸Re-labelled anti-CD66 monoclonal antibody. Patients, methods: For 49 patients with high risk leukaemia (24 men, 25 women, age: 44 ± 12 years) the residence times were determined for the injected ¹⁸⁸Re-labelled anti-CD66 antibodies (1.3 ± 0.4 GBq, 5–7 GBq/mg protein, >95% ¹⁸⁸Re bound to the antibody) based on 5 measurements (1.5, 3, 20, 26, and 44 h p.i.) using planar conjugate view gamma camera images (complete method). In a simplified method the residence times were calculated based on a single measurement 3 h p.i. Results: The residence times for kidneys, liver, red bone marrow, spleen and remainder of body for the complete method were 0.4 ± 0.2 h, 1.9 ± 0.8 h, 7.8 ± 2.1 h, 0.6 ± 0.3 h and 8.6 ± 2.1 h, respectively. For all organs a linear correlation exists between the residence times of the complete method and the simplified method with the slopes (correlation coefficients R > 0.89) of 0.89, 0.99, 1.23, 1.13 and 1.09 for kidneys, liver, red bone marrow, spleen and remainder of body, respectively. Conclusion: The proposed approach allows reliable prediction of biokinetics of ¹⁸⁸Re-labelled anti-CD66 monoclonal antibody biodistribution with a single study. Efficient pretherapeutic estimation of organ absorbed dose may be possible, provided that a more stable anti-CD66 antibody preparation is available.

Zusammenfassung

Ziel: Für die therapeutische Anwendung von Radiopharmaka wird die Aktivität individuell bestimmt. Hier untersuchen wir die Genauigkeit für eine vereinfachte Methode zur Bestimmung der Verweildauern für mit ¹⁸⁸Re markierten monoklonalen anti-CD66-Antikörpern. Patienten, Methoden: Bei 49 Patienten mit Hochrisiko-Leukämie (24 Männer, 25 Frauen, Lebensalter: 44 ± 12 Jahre) wurden die Verweildauern für die injizierten ¹⁸⁸Re-markierten anti- CD66-Antikörper (1,3 ± 0,4 GBq, 5–7 GBq/mg Protein, >95% ¹⁸⁸Re gebunden an den Antikörper) auf der Grundlage von 5 planaren Gammakamera-Messungen (1,5 h, 3, 20, 26, und 44 h p.i.) bestimmt (vollständige Methode). In einem vereinfachten Verfahren wurden die Verweildauern, nur auf der Messung 3 h p.i. basiert, berechnet. Ergebnisse: Die nach der vollständigen Methode berechneten Verweildauern für die Nieren, die Leber, das rote Knochenmark, die Milz und den Restkörper betrugen 0,4 ± 0,2 h, 1,9 ± 0,8 h, 7,8 ± 2,1 h, 0,6 ± 0,3 h und 8,6 ± 2,1 h. Für alle Organe wurde ein linearer Zusammenhang zwischen den Verweildauern der vollständigen und der vereinfachten Methode gefunden. Die Korrelationskoeffizienten R waren größer als 0,89 und die Steigungen der Regressionsgeraden waren 0,89, 0,99, 1,23, 1,13 und 1,09 für die Nieren, die Leber, das rote Knochenmark, die Milz und den Restkörper. Schlussfolgerung: Die vorgeschlagene Methode ermöglicht die Bestimmung der Bioverteilung von ¹⁸⁸Re-markiertem anti-CD66-Antikörper mit einer einzeitigen Messung 3 h p.i. und könnte mit stabiler markierten CD66-Antikörpern eine schnelle und zuverlässige prätherapeutische Abschätzung der Strahlenexposition erlauben.

• References

• 1 Alexander C, Holländer M, Schmidt W. et al. Kinetics and Dosimetry of MAb-170: Evaluation of possibilities for intraperitoneal radioimmunotherapy. Nuklearmedizin 2001; 20: 207-14.
  Article in Thieme ConnectGoogle Scholar
• 2 Buchmann I, Meyer RG, Herr W. et al. Radioimmunotherapy for treatment of acute myeloid leukaemia and myelodysplastic syndrome: Conceptual changes. Nuklearmedizin 2005; 44: 107-17.
  Article in Thieme ConnectPubMedGoogle Scholar
• 3 Bunjes D, Buchmann I, Duncker C. et al. Rhenium 188-labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with high-risk acute myeloid leukemia or myelodysplastic syndrome: results of a phase I-II study. Blood 2001; 98: 565-72.
  CrossrefPubMedGoogle Scholar
• 4 Dietlein M, Dressler J, Farahati J. et al. Procedure guidelines for radioiodine therapy of differenti- ated thyroid cancer (version 2). Nuklearmedizin 2004; 43: 115-20.
  Article in Thieme ConnectPubMedGoogle Scholar
• 5 Fischer M, Behr T, Grünwald F. et al. Guideline for radioimmunotherapy of rituximab relapsed or refractory CD20(+) follicular B-cell non-Hodgkin’s lymphoma. Nuklearmedizin 2004; 43: 171-6.
  Article in Thieme ConnectPubMedGoogle Scholar
• 6 Forrer F, Uusijarvi H, Waldherr C. et al. A comparison of ¹¹¹In-DOTATOC and ¹¹¹In-DOTATATE: biodistribution and dosimetry in the same patients with metastatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2004; 31: 1257-62.
  PubMedGoogle Scholar
• 7 Glatting G, Landmann M, Kull T. et al. Internal radionuclide therapy: The UlmDos software for treatment planning. Med Phys 2005; 32: 2399-405.
  CrossrefPubMedGoogle Scholar
• 8 Helisch A, Förster GJ, Reber H. et al. Pre-therapeutic dosimetry and biodistribution of ⁸⁶Y-DOTA-Phe1-Tyr3-octreotide versus 111Inpentetreotide in patients with advanced neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2004; 31: 1386-92.
  PubMedGoogle Scholar
• 9 Jamar F, Barone R, Mathieu I. et al. ⁸⁶Y-DOTA0)-D-Phe1-Tyr3-octreotide (SMT487) – a phase 1 clinical study: pharmacokinetics, biodistribution and renal protective effect of different regimens of amino acid co-infusion. Eur J Nucl Med Mol Imaging 2003; 30: 510-8.
  CrossrefPubMedGoogle Scholar
• 10 Kotzerke J, Glatting G, Seitz U. et al. Radioimmunotherapy for the intensification of conditioning before stem cell transplantation: differences in dosimetry and biokinetics of ¹⁸⁸Re- and ^99mTc-labeled anti-NCA-95 MAbs. J Nucl Med 2000; 41: 531-7.
  PubMedGoogle Scholar
• 11 Kull T, Ruckgaber J, Weller R. et al. Quantitative imaging of yttrium-86 PET with the ECAT EXACT HR+ in 2D mode. Cancer Biother Radiopharm 2004; 19: 482-90.
  CrossrefPubMedGoogle Scholar
• 12 Reske SN, Gloeckner W, Schwarz A. et al. Radioimmunoimaging for diagnosis of bone marrow involvement in breast cancer and malignant lymphoma. Lancet 1989; 2: 299-301.
  PubMedGoogle Scholar
• 13 Reske SN, Bunjes D, Buchmann I. et al. Targeted bone marrow irradiation in the conditioning of high risk leukemia prior to stem cell transplantation. Eur J Nucl Med 2001; 28: 807-15.
  CrossrefPubMedGoogle Scholar
• 14 Schneider P, Körber C, Körber-Hafner N. et al. Does an individual estimation of half-life improve the results of radioiodine therapy of Graves’ disease?. Nuklearmedizin 2002; 41: 240-244.
  Article in Thieme ConnectPubMedGoogle Scholar
• 15 Seitz U, Neumaier B, Glatting G. et al. Preparation and evaluation of the rhenium-188-labelled anti- NCA antigen monoclonal antibody BW 250/183 for radioimmunotherapy of leukaemia. Eur J Nucl Med 1999; 26: 1265-73.
  CrossrefPubMedGoogle Scholar
• 16 Sgouros G, Squeri S, Ballangrud AM. et al. Patient- specific, 3-dimensional dosimetry in Non- Hodgkin’s lymphoma patients treated with ¹³¹I-anti-B1 antibody: Assessment of tumor doseresponse. J Nucl Med 2003; 44: 260-8.
  PubMedGoogle Scholar
• 17 Sharkey RM, Brenner A, Burton J. et al. Radioimmunotherapy of Non-Hodgkin’s lymphoma with ⁹⁰Y-DOTA humanized anti-CD22 IgG (⁹⁰Y-Epratuzumab): Do tumor targeting and dosimetry predict therapeutic response?. J Nucl Med 2003; 44: 2000-18.
  PubMedGoogle Scholar
• 18 Siantar CH, Vetter K, DeNardo GL. et al. Treatment planning for molecular targeted radionuclide therapy. Cancer Biother Radiopharm 2002; 17: 267-80.
  CrossrefPubMedGoogle Scholar
• 19 Siegel JA, Thomas SR, Stubbs JB. et al. MIRD pamphlet no. 16: Techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates. J Nucl Med 1999; 40: 37-61S.
  Google Scholar
• 20 Stabin MG, Sparks RB, Crowe E. OLINDA/ EXM: The second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med 2005; 46: 1023-7.
  PubMedGoogle Scholar
• 21 Strand SE, Jonsson BA, Ljungberg M. et al. Radioimmunotherapy dosimetry--a review. Acta Oncol 1993; 32: 807-17.
  CrossrefPubMedGoogle Scholar
• 22 Thomas SR. Options for radionuclide therapy: From fixed activity to patient-specific treatment planning. Cancer Biother Radiopharm 2002; 17: 71-82.
  CrossrefPubMedGoogle Scholar