PMID- 37031346
OWN - NLM
STAT- MEDLINE
DCOM- 20230411
LR  - 20230414
IS  - 2399-3642 (Electronic)
IS  - 2399-3642 (Linking)
VI  - 6
IP  - 1
DP  - 2023 Apr 8
TI  - Proton boron capture therapy (PBCT) induces cell death and mitophagy in a 
      heterotopic glioblastoma model.
PG  - 388
LID - 10.1038/s42003-023-04770-w [doi]
LID - 388
AB  - Despite aggressive therapeutic regimens, glioblastoma (GBM) represents a deadly 
      brain tumor with significant aggressiveness, radioresistance and chemoresistance, 
      leading to dismal prognosis. Hypoxic microenvironment, which characterizes GBM, 
      is associated with reduced therapeutic effectiveness. Moreover, current 
      irradiation approaches are limited by uncertain tumor delineation and severe side 
      effects that comprehensively lead to unsuccessful treatment and to a worsening of 
      the quality of life of GBM patients. Proton beam offers the opportunity of 
      reduced side effects and a depth-dose profile, which, unfortunately, are coupled 
      with low relative biological effectiveness (RBE). The use of radiosensitizing 
      agents, such as boron-containing molecules, enhances proton RBE and increases the 
      effectiveness on proton beam-hit targets. We report a first preclinical 
      evaluation of proton boron capture therapy (PBCT) in a preclinical model of GBM 
      analyzed via mu-positron emission tomography/computed tomography (muPET-CT) 
      assisted live imaging, finding a significant increased therapeutic effectiveness 
      of PBCT versus proton coupled with an increased cell death and mitophagy. Our 
      work supports PBCT and radiosensitizing agents as a scalable strategy to treat 
      GBM exploiting ballistic advances of proton beam and increasing therapeutic 
      effectiveness and quality of life in GBM patients.
CI  - (c) 2023. The Author(s).
FAU - Cammarata, Francesco Paolo
AU  - Cammarata FP
AD  - Institute of Molecular Bioimaging and Physiology, National Research Council, 
      IBFM-CNR, Cefalu, Italy.
AD  - National Institute for Nuclear Physics, Laboratori Nazionali del Sud, INFN-LNS, 
      Catania, Italy.
FAU - Torrisi, Filippo
AU  - Torrisi F
AD  - Department of Biomedical and Biotechnological Sciences, University of Catania, 
      Catania, Italy.
FAU - Vicario, Nunzio
AU  - Vicario N
AUID- ORCID: 0000-0001-5934-3962
AD  - Department of Biomedical and Biotechnological Sciences, University of Catania, 
      Catania, Italy.
AD  - Molecular Preclinical and Translational Imaging Research Center - IMPRonTe, 
      University of Catania, Catania, Italy.
FAU - Bravata, Valentina
AU  - Bravata V
AD  - Institute of Molecular Bioimaging and Physiology, National Research Council, 
      IBFM-CNR, Cefalu, Italy.
FAU - Stefano, Alessandro
AU  - Stefano A
AD  - Institute of Molecular Bioimaging and Physiology, National Research Council, 
      IBFM-CNR, Cefalu, Italy.
FAU - Salvatorelli, Lucia
AU  - Salvatorelli L
AD  - Department G.F. Ingrassia, Azienda Ospedaliero-Universitaria 
      "Policlinico-Vittorio Emanuele" Anatomic Pathology, University of Catania, 
      Catania, Italy.
FAU - D'Aprile, Simona
AU  - D'Aprile S
AD  - Department of Biomedical and Biotechnological Sciences, University of Catania, 
      Catania, Italy.
FAU - Giustetto, Pierangela
AU  - Giustetto P
AD  - Department of Biomedical and Biotechnological Sciences, University of Catania, 
      Catania, Italy.
FAU - Forte, Giusi Irma
AU  - Forte GI
AD  - Institute of Molecular Bioimaging and Physiology, National Research Council, 
      IBFM-CNR, Cefalu, Italy.
FAU - Minafra, Luigi
AU  - Minafra L
AUID- ORCID: 0000-0003-3112-4519
AD  - Institute of Molecular Bioimaging and Physiology, National Research Council, 
      IBFM-CNR, Cefalu, Italy.
FAU - Calvaruso, Marco
AU  - Calvaruso M
AD  - Institute of Molecular Bioimaging and Physiology, National Research Council, 
      IBFM-CNR, Cefalu, Italy.
FAU - Richiusa, Selene
AU  - Richiusa S
AD  - Institute of Molecular Bioimaging and Physiology, National Research Council, 
      IBFM-CNR, Cefalu, Italy.
FAU - Cirrone, Giuseppe Antonio Pablo
AU  - Cirrone GAP
AUID- ORCID: 0000-0001-5733-9281
AD  - National Institute for Nuclear Physics, Laboratori Nazionali del Sud, INFN-LNS, 
      Catania, Italy.
FAU - Petringa, Giada
AU  - Petringa G
AD  - National Institute for Nuclear Physics, Laboratori Nazionali del Sud, INFN-LNS, 
      Catania, Italy.
FAU - Broggi, Giuseppe
AU  - Broggi G
AUID- ORCID: 0000-0003-2576-6523
AD  - Department G.F. Ingrassia, Azienda Ospedaliero-Universitaria 
      "Policlinico-Vittorio Emanuele" Anatomic Pathology, University of Catania, 
      Catania, Italy.
FAU - Cosentino, Sebastiano
AU  - Cosentino S
AD  - Nuclear Medicine Department, Cannizzaro Hospital, Catania, Italy.
FAU - Scopelliti, Fabrizio
AU  - Scopelliti F
AD  - Radiopharmacy Laboratory Nuclear Medicine Department, Cannizzaro Hospital, 
      Catania, Italy.
FAU - Magro, Gaetano
AU  - Magro G
AD  - Department G.F. Ingrassia, Azienda Ospedaliero-Universitaria 
      "Policlinico-Vittorio Emanuele" Anatomic Pathology, University of Catania, 
      Catania, Italy.
FAU - Porro, Danilo
AU  - Porro D
AD  - Institute of Molecular Bioimaging and Physiology, National Research Council, 
      IBFM-CNR, Cefalu, Italy.
FAU - Libra, Massimo
AU  - Libra M
AD  - Department of Biomedical and Biotechnological Sciences, University of Catania, 
      Catania, Italy.
FAU - Ippolito, Massimo
AU  - Ippolito M
AD  - Nuclear Medicine Department, Cannizzaro Hospital, Catania, Italy.
FAU - Russo, Giorgio
AU  - Russo G
AUID- ORCID: 0000-0003-1493-1087
AD  - Institute of Molecular Bioimaging and Physiology, National Research Council, 
      IBFM-CNR, Cefalu, Italy. giorgio-russo@cnr.it.
AD  - National Institute for Nuclear Physics, Laboratori Nazionali del Sud, INFN-LNS, 
      Catania, Italy. giorgio-russo@cnr.it.
FAU - Parenti, Rosalba
AU  - Parenti R
AUID- ORCID: 0000-0002-1614-4696
AD  - Department of Biomedical and Biotechnological Sciences, University of Catania, 
      Catania, Italy. parenti@unict.it.
AD  - Molecular Preclinical and Translational Imaging Research Center - IMPRonTe, 
      University of Catania, Catania, Italy. parenti@unict.it.
FAU - Cuttone, Giacomo
AU  - Cuttone G
AD  - National Institute for Nuclear Physics, Laboratori Nazionali del Sud, INFN-LNS, 
      Catania, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230408
PL  - England
TA  - Commun Biol
JT  - Communications biology
JID - 101719179
RN  - 0 (Protons)
RN  - N9E3X5056Q (Boron)
RN  - 0 (Radiation-Sensitizing Agents)
SB  - IM
MH  - Humans
MH  - *Glioblastoma/drug therapy/radiotherapy/pathology
MH  - Protons
MH  - Boron
MH  - Mitophagy
MH  - Quality of Life
MH  - *Radiation-Sensitizing Agents/pharmacology
MH  - Cell Death
MH  - Tumor Microenvironment
PMC - PMC10082834
COIS- The authors declare no competing interests.
EDAT- 2023/04/09 06:00
MHDA- 2023/04/11 06:42
PMCR- 2023/04/08
CRDT- 2023/04/08 23:23
PHST- 2022/10/01 00:00 [received]
PHST- 2023/03/28 00:00 [accepted]
PHST- 2023/04/11 06:42 [medline]
PHST- 2023/04/08 23:23 [entrez]
PHST- 2023/04/09 06:00 [pubmed]
PHST- 2023/04/08 00:00 [pmc-release]
AID - 10.1038/s42003-023-04770-w [pii]
AID - 4770 [pii]
AID - 10.1038/s42003-023-04770-w [doi]
PST - epublish
SO  - Commun Biol. 2023 Apr 8;6(1):388. doi: 10.1038/s42003-023-04770-w.