Preclinical Development of [211At]meta- astatobenzylguanidine ([211At]MABG) as an Alpha Particle Radiopharmaceutical Therapy for Neuroblastoma.
3-Iodobenzylguanidine
/ adverse effects
Alpha Particles
/ therapeutic use
Animals
Astatine
/ therapeutic use
Guanidines
/ therapeutic use
Humans
Iodine Radioisotopes
/ therapeutic use
Mice
Mice, Inbred NOD
Neoplasm Recurrence, Local
/ drug therapy
Neuroblastoma
/ drug therapy
Radiopharmaceuticals
/ adverse effects
Tissue Distribution
Tumor Cells, Cultured
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 09 2022
15 09 2022
Historique:
received:
09
03
2022
revised:
09
06
2022
accepted:
19
07
2022
pubmed:
22
7
2022
medline:
17
9
2022
entrez:
21
7
2022
Statut:
ppublish
Résumé
[131I]meta-iodobenzylguanidine ([131I]MIBG) is a targeted radiotherapeutic administered systemically to deliver beta particle radiation in neuroblastoma. However, relapses in the bone marrow are common. [211At]meta-astatobenzylguanidine ([211At] MABG) is an alpha particle emitter with higher biological effectiveness and short path length which effectively sterilizes microscopic residual disease. Here we investigated the safety and antitumor activity [211At]MABG in preclinical models of neuroblastoma. We defined the maximum tolerated dose (MTD), biodistribution, and toxicity of [211At]MABG in immunodeficient mice in comparison with [131I]MIBG. We compared the antitumor efficacy of [211At]MABG with [131I]MIBG in three murine xenograft models. Finally, we explored the efficacy of [211At]MABG after tail vein xenografting designed to model disseminated neuroblastoma. The MTD of [211At]MABG was 66.7 MBq/kg (1.8 mCi/kg) in CB17SC scid-/- mice and 51.8 MBq/kg (1.4 mCi/kg) in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice. Biodistribution of [211At]MABG was similar to [131I]MIBG. Long-term toxicity studies on mice administered with doses up to 41.5 MBq/kg (1.12 mCi/kg) showed the radiotherapeutic to be well tolerated. Both 66.7 MBq/kg (1.8 mCi/kg) single dose and fractionated dosing 16.6 MBq/kg/fraction (0.45 mCi/kg) × 4 over 11 days induced marked tumor regression in two of the three models studied. Survival was significantly prolonged for mice treated with 12.9 MBq/kg/fraction (0.35 mCi/kg) × 4 doses over 11 days [211At]MABG in the disseminated disease (IMR-05NET/GFP/LUC) model (P = 0.003) suggesting eradication of microscopic disease. [211At]MABG has significant survival advantage in disseminated models of neuroblastoma. An alpha particle emitting radiopharmaceutical may be effective against microscopic disseminated disease, warranting clinical development.
Identifiants
pubmed: 35861867
pii: 707126
doi: 10.1158/1078-0432.CCR-22-0400
pmc: PMC9475242
mid: NIHMS1826704
doi:
Substances chimiques
Astatine-211
0
Guanidines
0
Iodine Radioisotopes
0
Iodine-131
0
Radiopharmaceuticals
0
3-Iodobenzylguanidine
35MRW7B4AD
Astatine
XI595HAL7H
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
4146-4157Subventions
Organisme : NCI NIH HHS
ID : R01 CA219006
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA220500
Pays : United States
Informations de copyright
©2022 The Authors; Published by the American Association for Cancer Research.
Références
Clin Cancer Res. 2013 Nov 15;19(22):6173-82
pubmed: 24045179
Cancer Res. 1994 Oct 15;54(20):5414-9
pubmed: 7923174
Pediatr Blood Cancer. 2011 Dec 15;57(7):1124-9
pubmed: 21495159
Curr Radiopharm. 2008 Sep 1;1(3):177
pubmed: 20150978
Nat Rev Drug Discov. 2020 Sep;19(9):589-608
pubmed: 32728208
Cancer Res. 2016 Aug 1;76(15):4516-24
pubmed: 27261505
Cell Rep. 2019 Nov 5;29(6):1675-1689.e9
pubmed: 31693904
Mol Imaging Biol. 2012 Dec;14(6):735-42
pubmed: 22382618
J Pediatr Surg. 2007 Jul;42(7):1172-9
pubmed: 17618876
N Engl J Med. 2010 Jun 10;362(23):2202-11
pubmed: 20558371
Target Oncol. 2018 Apr;13(2):189-203
pubmed: 29423595
Semin Nucl Med. 2011 Sep;41(5):334-44
pubmed: 21803183
Bioconjug Chem. 1992 Nov-Dec;3(6):499-503
pubmed: 1463779
J Pediatr Hematol Oncol. 2003 Oct;25(10):769-73
pubmed: 14528098
J Nucl Biol Med (1991). 1991 Oct-Dec;35(4):220-3
pubmed: 1823822
Front Med (Lausanne). 2021 Jul 27;8:692436
pubmed: 34386508
Nucl Med Biol. 2017 Mar;46:43-49
pubmed: 28013121
Eur J Nucl Med Mol Imaging. 2003 Sep;30(9):1246-50
pubmed: 12811531
Int J Radiat Oncol Biol Phys. 1996 Apr 1;35(1):69-80
pubmed: 8641929
Br J Cancer. 1998 Jun;77(12):2061-8
pubmed: 9649115
Pharmaceutics. 2021 Jun 18;13(6):
pubmed: 34207408
J Nucl Med. 2019 Aug;60(8):1073-1079
pubmed: 30683761
Pediatr Blood Cancer. 2015 Jan;62(1):5-11
pubmed: 25175627
J Nucl Med. 2009 Jul;50(7):1153-60
pubmed: 19525452
Nucl Med Biol. 2008 Aug;35 Suppl 1:S35-48
pubmed: 18707633
Molecules. 2019 Nov 26;24(23):
pubmed: 31779154
Sci Rep. 2017 Dec 4;7(1):16878
pubmed: 29203879
J Nucl Med. 2005 Jun;46(6):1023-7
pubmed: 15937315
Theranostics. 2019 Feb 27;9(6):1538-1549
pubmed: 31037122
J Nucl Med. 1986 Sep;27(9):1490-7
pubmed: 3528417
Nat Rev Dis Primers. 2016 Nov 10;2:16078
pubmed: 27830764
Int J Cancer. 2000 Aug 1;87(3):412-22
pubmed: 10897048
Eur J Nucl Med Mol Imaging. 2018 Jun;45(6):999-1010
pubmed: 29350258
Pediatr Blood Cancer. 2017 Apr;64(4):
pubmed: 27654664
Eur J Cancer. 2014 Mar;50(4):801-15
pubmed: 24333097
EJNMMI Phys. 2020 Sep 22;7(1):58
pubmed: 32960387
J Clin Oncol. 2007 Mar 20;25(9):1054-60
pubmed: 17369569
J Nucl Med. 2008 Jan;49(1):30-8
pubmed: 18077533
Pediatr Blood Cancer. 2007 Dec;49(7):928-40
pubmed: 17066459
Pediatr Blood Cancer. 2022 Feb;69(2):e29396
pubmed: 34662499
Semin Radiat Oncol. 2021 Jan;31(1):3-11
pubmed: 33246634
Nucl Med Biol. 1996 Aug;23(6):851-6
pubmed: 8940730
J Clin Oncol. 2006 Jan 20;24(3):500-6
pubmed: 16421427
Biol Blood Marrow Transplant. 2015 Apr;21(4):673-81
pubmed: 25639769
Pediatr Blood Cancer. 2012 Oct;59(4):749-52
pubmed: 22052829
Cancer Biother Radiopharm. 2020 Aug;35(6):425-436
pubmed: 32077749
J Nucl Med. 2010 Feb;51(2):311-28
pubmed: 20080889
Int J Mol Imaging. 2012;2012:250834
pubmed: 23050139
Bioorg Med Chem. 2007 May 15;15(10):3430-6
pubmed: 17387017