Prolonged survival in secondary glioblastoma following local injection of targeted alpha therapy with ²¹³Bi-substance P analogue

Journal Article · Mon Apr 30 00:00:00 EDT 2018 · European Journal of Nuclear Medicine and Molecular Imaging

DOI:https://doi.org/10.1007/s00259-018-4015-2· OSTI ID:1623599

Krolicki, Leszek ^[1]; Bruchertseifer, Frank ^[2]; Kunikowska, Jolanta ^[3]; Koziara, Henryk ^[4]; Królicki, Bartosz ^[4]; Jakuciński, Maciej ^[5]; Pawlak, Dariusz ^[6]; Apostolidis, Christos ^[2]; Mirzadeh, Saed ^[7]; Rola, Rafał ^[8]; Merlo, Adrian ^[9]; Morgenstern, Alfred ^[2]

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1. Medical Univ. of Warsaw (Poland). Dept. of Nuclear Medicine; DOE/OSTI
2. European Commission, Karlsruhe (Germany). Joint Research Centre, Directorate for Nuclear Safety and Security
3. Medical Univ. of Warsaw (Poland). Dept. of Nuclear Medicine
4. Inst. of Psychiatry and Neurology, Warsaw (Poland). Dept. of Neurosurgery
5. Brodnowski Hospital, Warsaw (Poland). Dept. of Nuclear Medicine
6. National Centre for Nuclear Research, Warsaw (Poland). Radioisotope Centre POLATOM
7. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Nuclear Security and Isotope Technology Division, Nuclear and Radiochemistry Group
8. Military Inst. of Aviation Medicine, Warsaw (Poland). Dept. of Neurology
9. Univ. of Basel (Switzerland); Bern Univ. (Switzerland). Neurosurgery

Background Glioblastoma multiforme (GBM), the most common malignant brain tumor, mainly manifests as a primary de novo and less frequently as a secondary glial neoplasm. GBM has been demonstrated to overexpress the NK-1 receptor and substance P can be used as a ligand for targeted therapy. Alpha emitters, e.g. ²¹³Bi, that deposit their high energy within a short range allow the selective irradiation of tumor cells while sparing adjacent neuronal structures. Material and methods Among 50 glioma patients of different subtypes that have to date been treated with targeted alpha therapy at the Medical University Warsaw, we report here the data on nine patients with secondary GBM. Following surgery, chemo- and radiotherapy, recurrent GBM was treated by intracavitary injection of 1–6 doses of 0.9–2.3 GBq ²¹³Bi- DOTA-[Thi⁸ ,Met(O₂)¹¹]-substance P (²¹³Bi-DOTA-SP) in 2-month intervals. ⁶⁸Ga-DOTA-[Thi⁸ ,Met(O₂)¹¹]-substance P (⁶⁸Ga-DOTA-SP) was coinjected with the therapeutic doses to assess biodistribution using PET/CT. Therapeutic response was monitored with MRI. Results Treatment with activities ranging from 1.4 to 9.7 (median 5.8) GBq ²¹³Bi- DOTA-SP was well tolerated with only mild transient adverse reactions, mainly headaches due to a transient perfocal edema reaction. The median progression free survival and overall survival time following the initiation of alpha therapy was 5.8 and 16.4 months, respectively. The median overall survival time from the first diagnosis was 52.3 months. Two out of nine patients are still alive 39 and 51 months, respectively, after the initiation of the therapy.

• Research Organization: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
• Sponsoring Organization: European Association of Nuclear Medicine (EANM); USDOE Office of Science (SC), Nuclear Physics (NP)
• Grant/Contract Number: AC05-00OR22725
• OSTI ID: 1623599
• Alternate ID(s): OSTI ID: 22725290
• Journal Information: European Journal of Nuclear Medicine and Molecular Imaging, Journal Name: European Journal of Nuclear Medicine and Molecular Imaging Journal Issue: 9 Vol. 45; ISSN 1619-7070
• Publisher: Springer Nature
• Country of Publication: United States
• Language: English

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