Kinetics and dosimetry of MAb-170: Evaluation of possibilities for intraperitoneal radioimmunotherapy

Ch. Alexander; M. Holländer; W. Schmidt; C.-M. Kirsch

doi:10.1055/s-0038-1625283

Nuklearmedizin - NuclearMedicine, Table of Contents

Nuklearmedizin 2001; 40(06): 207-214
DOI: 10.1055/s-0038-1625283

Editorial

Schattauer GmbH

Kinetics and dosimetry of MAb-170: Evaluation of possibilities for intraperitoneal radioimmunotherapy

Biokinetik und Dosimetrie mit dem monoklonalen Antikörper MAb-170: Evaluation der Möglichkeit einer intraperitonealen Radioimmuntherapie

Authors

Ch. Alexander

¹Abteilung für Nuklearmedizin
M. Holländer

²Frauenklinik und Poliklinik, Universitätskliniken des Saarlandes, Homburg/Saar, Germany
W. Schmidt

²Frauenklinik und Poliklinik, Universitätskliniken des Saarlandes, Homburg/Saar, Germany
C.-M. Kirsch

¹Abteilung für Nuklearmedizin

Abstract

Summary

The monoclonal antibody MAb-170 is directed against adenocarcinomas of different origin. Recent experience in radioimmunoscintigraphy revealed a positive uptake of this MAb in peritoneal metastases of ovarian carcinoma (FIGO lll/IV). Aim: The present investigation should clarify the question whether this antibody could be of use in an adjuvant intraperitoneal radioimmunotherapy (RIT) in patients with minimal residual disease after first-look surgery. Methods: Four patients underwent intraperitoneal application of Tc-99m MAb-170. Subsequent quantitative whole-body scintigraphy, serum and urine sampling were performed for a 48 h period. In one case tumour tissue specimen were sampled during the first surgical procedure 15 h p.L Results: The quantitative evaluation revealed no relevant accumulation in liver, spleen and bone marrow never exceeding 5 % of the whole-body activity. The critical organs are the kidneys that showed 8 to 11 % uptake at 24 h pi. The effective serum curve had a maximum at 24 h pi, the second phase gave a elimination half-time of 53 h. Assuming the worst case, the mean dose to red bone marrow was 0.3 Gy/370 MBq injected dose (ID). Conclusion: These results confirm that a RIT with Re-186 MAb-170 is feasible with activities of up to 3.7 GBq. A kit for labelling MAb-170 with Perrhenate is under investigation.

Zusammenfassung

Der monoklonale Antikörper MAb-170 ist gegen tumorassoziiertes Antigen von Adenokarzinomen gerichtet. Erste Erfahrungen in der Radioimmunszintigraphie (RIS) zeigen vielversprechende Ergebnisse in der Diagnostik von Ovarialkarzinomen. Ziel: Die durchgeführten Untersuchungen sollten klären, ob ein Einsatz dieses Antikörpers - nach Markierung mit Re-186 - zur adjuvanten intraperitonealen Radioimmuntherapie (RIT) von Patientinnen mit Peritonealkarzinose und »minimal residual disease« nach First-look-OP sinnvoll ist. Methoden: Bei 4 Patientinnen wurde Tc-99m MAb-170 intraperitoneal appliziert. Ganzkörperszintigramme, Urinausscheidung und Serumaktivitätskonzentration wurden anschließend über 48 h registriert. In einem Fall wurden 15 h nach Applikation im Rahmen der First-look-OP Gewebeproben gewonnen. Ergebnisse: Die Knochenmarkdosis betrug 0,35 Gy/370 MBq Re-186 MAb-170, die Nierendosis (kritisches Organ) 0,37 Gy. Die Akkumulation in Leber, Milz, Herz und Lunge war gering bis mäßig (<5,4 % ID), die mittlere Tumordosis wurde auf 25 Gy/370 MBq geschätzt. Der effektive Serumaktivitätsverlauf zeigte ein Maximum 24 h p.i., die Halbwertszeit der Eliminationphase betrug 53 Stunden. Schlussfolgerurig: Die vorliegenden Ergebnisse rücken eine RIT mit Re-186-markiertem MAb-170 in den Bereich des Möglichen mit Therapieaktivitäten bis 1,8 GBq.

Keywords

Radioimmunotherapy - monoclonal antibodies - ovarian cancer - peritoneal carcinosis - dosimetry

Schlüsselwörter

Radioimmuntherapie - monoklonale Antikörper - Ovarialkarzinom - Peritonealkarzinose - Dosimetrie

Full Text

References

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