Retooling a Blood-Based Biomarker: Phase I Assessment of the High-Affinity CA19-9 Antibody HuMab-5B1 for Immuno-PET Imaging of Pancreatic Cancer.
Adenocarcinoma
/ blood
Aged
Antibodies, Monoclonal, Humanized
/ administration & dosage
Biomarkers, Tumor
/ blood
CA-19-9 Antigen
/ blood
Follow-Up Studies
Humans
Male
Middle Aged
Pancreatic Neoplasms
/ blood
Positron Emission Tomography Computed Tomography
/ methods
Prognosis
Radiopharmaceuticals
/ administration & dosage
Tissue Distribution
Zirconium
/ chemistry
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:
01 12 2019
01 12 2019
Historique:
received:
12
11
2018
revised:
14
05
2019
accepted:
06
09
2019
pubmed:
22
9
2019
medline:
22
9
2020
entrez:
22
9
2019
Statut:
ppublish
Résumé
In patients with cancer who have an abnormal biomarker finding, the source of the biomarker in the bloodstream must be located for confirmation of diagnosis, staging, and therapy planning. We evaluated if immuno-PET with the radiolabeled high-affinity antibody HuMab-5B1 (MVT-2163), binding to the cancer antigen CA19-9, can identify the source of elevated biomarkers in patients with pancreatic cancer. In this phase I dose-escalating study, 12 patients with CA19-9-positive metastatic malignancies were injected with MVT-2163. Within 7 days, all patients underwent a total of four whole-body PET/CT scans. A diagnostic CT scan was performed prior to injection of MVT-2163 to correlate findings on MVT-2163 PET/CT. Immuno-PET with MVT-2163 was safe and visualized known primary tumors and metastases with high contrast. In addition, radiotracer uptake was not only observed in metastases known from conventional CT, but also seen in subcentimeter lymph nodes located in typical metastatic sites of pancreatic cancer, which were not abnormal on routine clinical imaging studies. A significant fraction of the patients demonstrated very high and, over time, increased uptake of MVT-2163 in tumor tissue, suggesting that HuMab-5B1 labeled with beta-emitting radioisotopes may have the potential to deliver therapeutic doses of radiation to cancer cells. Our study shows that the tumor antigen CA19-9 secreted to the circulation can be used for sensitive detection of primary tumors and metastatic disease by immuno-PET. This significantly broadens the number of molecular targets that can be used for PET imaging and offers new opportunities for noninvasive characterization of tumors in patients.
Identifiants
pubmed: 31540979
pii: 1078-0432.CCR-18-3667
doi: 10.1158/1078-0432.CCR-18-3667
pmc: PMC7052809
mid: NIHMS1539942
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Biomarkers, Tumor
0
CA-19-9 Antigen
0
Radiopharmaceuticals
0
Zirconium
C6V6S92N3C
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7014-7023Subventions
Organisme : NCI NIH HHS
ID : HHSN261201300060C
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA222049
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA232130
Pays : United States
Informations de copyright
©2019 American Association for Cancer Research.
Références
Clin Cancer Res. 2011 Mar 1;17(5):1024-32
pubmed: 21343375
Eur J Nucl Med Mol Imaging. 2014 Nov;41(11):2093-105
pubmed: 25143071
Cancer Lett. 2016 Oct 10;381(1):217-36
pubmed: 26742462
Cancer Immunol Immunother. 2009 Sep;58(9):1397-405
pubmed: 19190907
PLoS One. 2015 Oct 02;10(10):e0139049
pubmed: 26431551
Nat Rev Drug Discov. 2007 May;6(5):349-56
pubmed: 17431406
CA Cancer J Clin. 2018 Jan;68(1):7-30
pubmed: 29313949
Int J Biol Markers. 1988 Jul-Sep;3(3):177-84
pubmed: 3230337
Mol Cancer Ther. 2017 Jan;16(1):124-133
pubmed: 28062708
Nucl Med Biol. 2009 Oct;36(7):729-39
pubmed: 19720285
N Engl J Med. 2017 Jan 12;376(2):125-135
pubmed: 28076709
J Nucl Med. 2013 Nov;54(11):1876-82
pubmed: 24029655
Nat Rev Gastroenterol Hepatol. 2018 Jun;15(6):333-348
pubmed: 29717230
Pancreas. 2016 Jul;45(6):789-95
pubmed: 26745859
Nat Protoc. 2010 Apr;5(4):739-43
pubmed: 20360768
Eur J Nucl Med. 1998 Jun;25(6):565-74
pubmed: 9618570
Cochrane Database Syst Rev. 2016 Jul 06;7:CD009323
pubmed: 27383694
N Engl J Med. 2014 Sep 11;371(11):1039-49
pubmed: 25207767
Mol Pharm. 2017 Mar 6;14(3):908-915
pubmed: 28191976
J Surg Res. 2011 Oct;170(2):169-78
pubmed: 21601881
Proc Natl Acad Sci U S A. 2015 Dec 29;112(52):15850-5
pubmed: 26668398
Ann Nucl Med. 1994 Aug;8(3):163-9
pubmed: 7811557
Adv Exp Med Biol. 2015;867:247-60
pubmed: 26530370
J Nucl Med. 2017 Sep;58(Suppl 2):83S-90S
pubmed: 28864618
Semin Nucl Med. 1999 Jan;29(1):41-8
pubmed: 9990682
J Nucl Med. 2018 Jan;59(1):3-12
pubmed: 28935835
Methods Enzymol. 1986;121:678-91
pubmed: 3523136
Lancet Oncol. 2018 Jun;19(6):825-833
pubmed: 29752180
J Nucl Med. 2018 Jan;59(1):161-166
pubmed: 28637800
J Nucl Med. 2018 Jun;59(6):900-906
pubmed: 29146695
Nat Rev Clin Oncol. 2019 Jan;16(1):11-26
pubmed: 30341417