Nuklearmedizin 2013; 52(01): 36-42
DOI: 10.3413/Nukmed-0510-12-06
Original article
Schattauer GmbH

Patients with recurrent glioblastoma multiforme

Initial experience with p-[131I]iodo-L-phenylalanine and external beam radiation therapyPatienten mit rezidivierendem Glioblastoma multiformeErste Erfahrungen mit p-[131I]Iod-L-phenylalanin und externen Strahlentherapie
F. A. Verburg
1   Department of Nuclear Medicine, University of Würzburg, Germany
4   Department of Nuclear Medicine, University of Aachen, Germany
,
R. Sweeney
2   Department of Radiotherapy and Radio - oncology, University of Würzburg, Germany
,
H. Hänscheid
1   Department of Nuclear Medicine, University of Würzburg, Germany
,
S. Dießl
1   Department of Nuclear Medicine, University of Würzburg, Germany
,
I. Israel
1   Department of Nuclear Medicine, University of Würzburg, Germany
,
M. Löhr
3   Department of Neurosurgery, University of Würzburg, Germany
,
G. H. Vince
3   Department of Neurosurgery, University of Würzburg, Germany
,
M. Flentje
2   Department of Radiotherapy and Radio - oncology, University of Würzburg, Germany
,
C. Reiners
1   Department of Nuclear Medicine, University of Würzburg, Germany
,
S. Samnick
1   Department of Nuclear Medicine, University of Würzburg, Germany
› Author Affiliations
Further Information

Publication History

received: 12 June 2012

accepted in revised form: 15 January 2012

Publication Date:
04 January 2018 (online)

Summary

Aim: The objective of this study was to assess the feasibility, dosimetry, tolerability and efficacy of systemically administrated p-[131I] - iodo-L-phenylalanine (131IPA) combined with hypo-fractionated external beam radiation therapy (EBRT) in patients with recurrent glioblastoma multiforme (GBM). Patients, methods: Five patients (2 women, 3 men, aged 27-69) with recurrent GBM and exhaustion of regular therapy options were included. All had a positive O-(2-[18F]Fluoroethyl)- L-tyrosine positron emission tomography (FET-PET) and pretherapeutic dosimetry was performed. Tumour targeting was verified by 131IPA-SPECT up to six days after radiotracer administration. After 131IPA therapy, patients were treated with hypo-fractionated EBRT in six fractions of 5 Gy (n = 4) or in eleven fractions of 2 Gy in one case. Results: Based on the individual dosimetry, the patients received a single intravenous administration of 2 to 7 GBq of 131IPA, resulting in radiation absorbed doses to the blood of 0.80–1.47 Gy. The treatment was well tolerated; only minor complaints of nausea and vomiting that responded to ondansetron and pantoprazol were noticed in the first two patients. After preventive medication, the last three patients had no complaints during therapy. In none of the patients a decrease of leukocyte or thrombocyte counts below the baseline level or the lower normal limit was observed. Tumour doses from 131IPA were low (≤ 1 Gy) and all patients died three to eight (median 5.5) months after therapy. Conclusion: In this initial experience, treatment of GBM with 131IPA in combination with EBRT was demonstrated to be safe and well tolerated, but less effective than suggested by the animal studies.

Zusammenfassung

Ziel dieser Studie war es, die Durchführbarkeit, Dosimetrie, Verträglichkeit und Wirksamkeit einer Therapie mit systemisch verabreichtem p-[131I]Iod-L-phenylalanin (131IPA) in Kombination mit einer hypo-fraktionierten externer Strahlentherapie (EBRT) bei Patienten mit Glioblastoma multiforme (GBM) zu untersuchen. Patienten, Methoden: Fünf Patienten (2 Frauen, 3 Männer, Alter 27–69 Jahre) mit rezidiviertem GBM wurden nach Ausschöpfung der regulären Therapiemöglichkeiten eingeschlossen. Bei allen lag eine positive O-(2-[18F]Fluorethyl)-L-tyrosin-Positronenemissionstomographie (FET-PET) vor und eine prätherapeutische Dosimetrie wurde durchgeführt. Die Aufnahme des Tracers in den Tumor wurde mittels 131IPA-SPECT nach bis zu sechs Tagen nach Tracer-Verabreichung verifiziert. Nach 131IPA-Therapie wurden die Patienten mit hypo-fraktionierter EBRT in sechs Fraktionen von 5 Gy (n = 4) bzw. in einem Fall in elf Fraktionen von 2 Gy behandelt. Ergebnisse: Abhängig von der individuellen Dosimetrie verabreichten wir den Patienten 2 bis 7 GBq 131IPA i. v., was zu Blutdosen von 0.80–1.47 Gy führte. Die Behandlung wurde gut vertragen; nur geringfügige Beschwerden von Übelkeit und Erbrechen, die mit Ondansetron und Pantoprazol therapierbar waren, wurden bei den ersten zwei Patienten beobachtet. Unter vorbeugender Medikamentengabe hatten die letzten drei Patienten keine Beschwerden während der Therapie. Bei keinem Patienten zeigte sich nach Therapie ein Abfall der Leukozytenoder Thrombozytenzahl unterhalb des Ausgangswertes oder unterhalb des unteren Referenzwerts. Die Tumordosen durch das 131IPA blieben niedrig (≤ 1 Gy) und alle Patienten starben drei bis acht (Median 5,5) Monate nach der Therapie. Schlussfolgerung: Die Behandlung des GBM mittels 131IPA in Kombination mit EBRT erwies sich als sicher und gut verträglich, aber weniger wirksam als es die Tierstudien erhoffen ließen.

 
  • References

  • 1 Common Terminology Criteria for Adverse Events v3.0 (CTCAE).. Rockville, MD: National Cancer Institute; 2006
  • 2 Baum RP, Kluge A, Gildehaus FJ. et al. Systemic endoradiotherapy with carrier-added 4-[131I]iodo-L-phenylalanine: Clinical proof-of-principle in refractory glioma. Nucl Med Mol Imaging 2011; 45: 299-307.
  • 3 Benua RS, Cicale NR, Sonenberg M, Rawson RW. The relation of radioiodine dosimetry to results and complications in the treatment of metastatic thyroid cancer. AJR 1962; 1962: 171-182.
  • 4 Goetz C, Riva P, Poepperl G. et al. Locoregional radioimmunotherapy in selected patients with malignant glioma: experiences, side effects and survival times. J Neurooncol 2003; 62: 321-328.
  • 5 Hellwig D, Ketter R, Romeike BF. et al. Prospective study of p-[123I]iodo-L-phenylalanine and SPECT for the evaluation of newly diagnosed cerebral lesions: specific confirmation of glioma. Eur J Nucl Med Mol Imaging 2010; 37: 2344-2353.
  • 6 Hellwig D, Menges M, Schneider G. et al. Radio-iodinated phenylalanine derivatives to image pancreatic cancer: a comparative study with [18F]flu- oro-2-deoxy-D-glucose in human pancreatic carcinoma xenografts and in inflammation models. Nucl Med Biol 2005; 32: 137-145.
  • 7 Heute D, Kostron H, von Guggenberg E. et al. Response of recurrent high-grade glioma to treatment with 90Y-DOTATOC. J Nucl Med 2010; 51: 397-400.
  • 8 Israel I, Blass G, Reiners C, Samnick S. Validation of an amino-acid-based radionuclide therapy plus external beam radiotherapy in heterotopic glioblastoma models. Nucl Med Biol 2011; 38: 451-460.
  • 9 Knox SJ, Sutherland W, Goris ML. Correlation of tumor sensitivity to low-dose-rate irradiation with G2/M-phase block and other radiobiological parameters. Radiat Res 1993; 135: 24-31.
  • 10 Kolbert KS, Pentlow KS, Pearson JR. et al. Prediction of absorbed dose to normal organs in thyroid cancer patients treated with 131I by use of 124I PET and 3-dimensional internal dosimetry software. J Nucl Med 2007; 48: 143-149.
  • 11 Langen KJ, Hamacher K, Weckesser M. et al. O-(2-[18F]fluoroethyl)-L-tyrosine: uptake mechanisms and clinical applications. Nucl Med Biol 2006; 33: 287-294.
  • 12 Lassmann M, Haenscheid H, Chiesa C. et al. EANM dosimetry committee series on standard operational procedures for pre-therapeutic dosimetry I: blood and bone marrow dosimetry in differentiated thyroid cancer therapy. Eur J Nucl Med Mol Imaging 2008; 35: 1405-1412.
  • 13 Merlo A, Hausmann O, Wasner M. et al. Locoregional regulatory peptide receptor targeting with the diffusible somatostatin analogue 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC): a pilot study in human gliomas. Clin Cancer Res 1999; 5: 1025-1033.
  • 14 Miller CR, Perry A. Glioblastoma. Arch Pathol Lab Med 2007; 131: 397-406.
  • 15 Pöpperl G, Kreth FW, Mehrkens JH. et al. FET PET for the evaluation of untreated gliomas: correlation of FET uptake and uptake kinetics with tumour grading. Eur J Nucl Med Mol Imaging 2007; 34: 1933-1942.
  • 16 Riva P, Franceschi G, Frattarelli M. et al. Loco-regional radioimmunotherapy of high-grade malignant gliomas using specific monoclonal antibodies labeled with 90Y: a phase I study. Clin Cancer Res 1999; 5: 3275s-3280s.
  • 17 Riva P, Franceschi G, Frattarelli M. et al. 131I radio-conjugated antibodies for the locoregional radioimmunotherapy of high-grade malignant glioma-phase I and II study. Acta Oncol 1999; 38: 351-359.
  • 18 Romeike BF, Hellwig D, Heimann A. et al. Action and efficacy of p-[131I]iodo-L-phenylalanine on primary human glioma cell cultures and rats with C6-gliomas. Anticancer Res 2004; 24: 3971-3976.
  • 19 Samnick S, Bader JB, Hellwig D. et al. Clinical value of iodine-123-alpha-methyl-L-tyrosine singlephoton emission tomography in the differential diagnosis of recurrent brain tumor in patients pretreated for glioma at follow-up. J Clin Oncol 2002; 20: 396-404.
  • 20 Samnick S, Hellwig D, Bader JB. et al. Initial evaluation of the feasibility of single photon emission tomography with p-[123 I]iodo-L-phenylalanine for routine brain tumour imaging. Nucl Med Commun 2002; 23: 121-130.
  • 21 Samnick S, Romeike BF, Lehmann T. et al. Efficacy of systemic radionuclide therapy with p-131I-iodo-L-phenylalanine combined with external beam photon irradiation in treating malignant gliomas. J Nucl Med 2009; 50: 2025-2032.
  • 22 Sgouros G, Knox SJ, Joiner MC. et al. MIRD continuing education: Bystander and low dose-rate effects: are these relevant to radionuclide therapy?. J Nucl Med 2007; 48: 1683-1691.
  • 23 Stupp R, Hegi ME, Mason WP. et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 2009; 10: 459-466.
  • 24 Vordermark D, Kolbl O, Ruprecht K. et al. Hypofractionated stereotactic re-irradiation: treatment option in recurrent malignant glioma. BMC Cancer 2005; 5: 55.
  • 25 Wick A, Felsberg J, Steinbach JP. et al. Efficacy and tolerability of temozolomide in an alternating weekly regimen in patients with recurrent glioma. J Clin Oncol 2007; 25: 3357-3361.