Norepinephrine transporter and vesicular monoamine transporter 2 tumor expression as a predictor of response to 131 I-MIBG in patients with relapsed/refractory neuroblastoma
Prior studies suggest that norepinephrine transporter (NET) and vesicular monoamine transporter 2 (VMAT2) mediate meta-iodobenzylguanidine (MIBG) uptake and retention in neuroblastoma tumors. We evaluated the relationship between NET and VMAT2 tumor expression and clinical response to I-MIBG therapy...
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| Veröffentlicht in: | Pediatric blood & cancer 2024-01, Vol.71 (1), p.e30743 |
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| creator | Batra, Vandana Gikandi, Ajami Pawel, Bruce Martinez, Daniel Granger, M Meaghan Marachelian, Araz Park, Julie R Maris, John M Vo, Kieuhoa T Matthay, Katherine K DuBois, Steven G |
| description | Prior studies suggest that norepinephrine transporter (NET) and vesicular monoamine transporter 2 (VMAT2) mediate meta-iodobenzylguanidine (MIBG) uptake and retention in neuroblastoma tumors. We evaluated the relationship between NET and VMAT2 tumor expression and clinical response to
I-MIBG therapy in patients with neuroblastoma.
Immunohistochemistry (IHC) was used to evaluate NET and VMAT2 protein expression levels on archival tumor samples (obtained at diagnosis or relapse) from patients with relapsed or refractory neuroblastoma treated with
I-MIBG. A composite protein expression H-score was determined by multiplying a semi-quantitative intensity value (0-3+) by the percentage of tumor cells expressing the protein.
Tumor samples and clinical data were available for 106 patients, of whom 28.3% had partial response (PR) or higher. NET H-score was not significantly associated with response (≥PR), though the percentage of tumor cells expressing NET was lower among responders (median 80% for ≥PR vs. 90% for |
| doi_str_mv | 10.1002/pbc.30743 |
| format | Article |
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I-MIBG therapy in patients with neuroblastoma.
Immunohistochemistry (IHC) was used to evaluate NET and VMAT2 protein expression levels on archival tumor samples (obtained at diagnosis or relapse) from patients with relapsed or refractory neuroblastoma treated with
I-MIBG. A composite protein expression H-score was determined by multiplying a semi-quantitative intensity value (0-3+) by the percentage of tumor cells expressing the protein.
Tumor samples and clinical data were available for 106 patients, of whom 28.3% had partial response (PR) or higher. NET H-score was not significantly associated with response (≥PR), though the percentage of tumor cells expressing NET was lower among responders (median 80% for ≥PR vs. 90% for <PR; p = .0014). VMAT2 H-score was not significantly associated with PR or higher versus less than PR, though patients with PR or higher had lower VMAT2 staining intensity (p = .005). VMAT2 H-score was significantly lower in patients with complete response (median 40 vs. 210 for patients with <complete response; p = .0049). VMAT2 H-scores were significantly higher in ganglioneuroblastoma (vs. neuroblastoma; p = .037), differentiated/poorly differentiated tumors (vs. undifferentiated; p = .0047), and tumors lacking MYCN amplification (vs. MYCN amplified; p = .0011).
Markers of lower NET and VMAT2 protein expression are associated with higher likelihood of response to
I-MIBG therapy in patients with relapsed/refractory neuroblastoma. Increased VMAT2 protein expression is associated with a more differentiated disease phenotype.</description><identifier>ISSN: 1545-5009</identifier><identifier>ISSN: 1545-5017</identifier><identifier>EISSN: 1545-5017</identifier><identifier>DOI: 10.1002/pbc.30743</identifier><identifier>PMID: 37885116</identifier><language>eng</language><publisher>United States</publisher><subject>3-Iodobenzylguanidine - therapeutic use ; Chronic Disease ; Humans ; N-Myc Proto-Oncogene Protein ; Neoplasm Recurrence, Local - drug therapy ; Neuroblastoma - drug therapy ; Norepinephrine Plasma Membrane Transport Proteins - metabolism ; Radiopharmaceuticals ; Vesicular Monoamine Transport Proteins - metabolism</subject><ispartof>Pediatric blood & cancer, 2024-01, Vol.71 (1), p.e30743</ispartof><rights>2023 Wiley Periodicals LLC.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c906-74b660fd4db721658d88c158846177ae222376711634209cd2b99fc2484bdf853</cites><orcidid>0000-0001-9556-106X ; 0000-0002-0146-2499 ; 0000-0003-3857-4782 ; 0000-0002-8088-7929 ; 0000-0002-9281-7485 ; 0000-0003-0882-738X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37885116$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Batra, Vandana</creatorcontrib><creatorcontrib>Gikandi, Ajami</creatorcontrib><creatorcontrib>Pawel, Bruce</creatorcontrib><creatorcontrib>Martinez, Daniel</creatorcontrib><creatorcontrib>Granger, M Meaghan</creatorcontrib><creatorcontrib>Marachelian, Araz</creatorcontrib><creatorcontrib>Park, Julie R</creatorcontrib><creatorcontrib>Maris, John M</creatorcontrib><creatorcontrib>Vo, Kieuhoa T</creatorcontrib><creatorcontrib>Matthay, Katherine K</creatorcontrib><creatorcontrib>DuBois, Steven G</creatorcontrib><title>Norepinephrine transporter and vesicular monoamine transporter 2 tumor expression as a predictor of response to 131 I-MIBG in patients with relapsed/refractory neuroblastoma</title><title>Pediatric blood & cancer</title><addtitle>Pediatr Blood Cancer</addtitle><description>Prior studies suggest that norepinephrine transporter (NET) and vesicular monoamine transporter 2 (VMAT2) mediate meta-iodobenzylguanidine (MIBG) uptake and retention in neuroblastoma tumors. We evaluated the relationship between NET and VMAT2 tumor expression and clinical response to
I-MIBG therapy in patients with neuroblastoma.
Immunohistochemistry (IHC) was used to evaluate NET and VMAT2 protein expression levels on archival tumor samples (obtained at diagnosis or relapse) from patients with relapsed or refractory neuroblastoma treated with
I-MIBG. A composite protein expression H-score was determined by multiplying a semi-quantitative intensity value (0-3+) by the percentage of tumor cells expressing the protein.
Tumor samples and clinical data were available for 106 patients, of whom 28.3% had partial response (PR) or higher. NET H-score was not significantly associated with response (≥PR), though the percentage of tumor cells expressing NET was lower among responders (median 80% for ≥PR vs. 90% for <PR; p = .0014). VMAT2 H-score was not significantly associated with PR or higher versus less than PR, though patients with PR or higher had lower VMAT2 staining intensity (p = .005). VMAT2 H-score was significantly lower in patients with complete response (median 40 vs. 210 for patients with <complete response; p = .0049). VMAT2 H-scores were significantly higher in ganglioneuroblastoma (vs. neuroblastoma; p = .037), differentiated/poorly differentiated tumors (vs. undifferentiated; p = .0047), and tumors lacking MYCN amplification (vs. MYCN amplified; p = .0011).
Markers of lower NET and VMAT2 protein expression are associated with higher likelihood of response to
I-MIBG therapy in patients with relapsed/refractory neuroblastoma. Increased VMAT2 protein expression is associated with a more differentiated disease phenotype.</description><subject>3-Iodobenzylguanidine - therapeutic use</subject><subject>Chronic Disease</subject><subject>Humans</subject><subject>N-Myc Proto-Oncogene Protein</subject><subject>Neoplasm Recurrence, Local - drug therapy</subject><subject>Neuroblastoma - drug therapy</subject><subject>Norepinephrine Plasma Membrane Transport Proteins - metabolism</subject><subject>Radiopharmaceuticals</subject><subject>Vesicular Monoamine Transport Proteins - metabolism</subject><issn>1545-5009</issn><issn>1545-5017</issn><issn>1545-5017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU1PFzEQxhuDEUQPfgHSIx4W-rrtHoEo_hPUC_dNt-2Gkt22dLogH8rvaBHk4GVeMr95MpMHoU-UnFBC2Gme7AknSvA36IBKITtJqNp7rcmwj94D3Da0J1K_Q_tcaS0p7Q_Q7x-p-ByizzelRVyLiZBTqb5gEx2-9xDstpiC1xSTWf9nGK7bmgr2v3LxACFFbAAb3DoXbG2TNOM2ySlC20yYcop33ffd-SUOEWdTg48V8EOoN41bTAbvToufi3nafsTRbyVNi4GaVvMBvZ3NAv7jSz5E11-_XF98665-Xu4uzq46O5C-U2LqezI74SbFaC-109pSqbXoqVLGM8a46lX7nwtGBuvYNAyzZUKLyc1a8kN0_CybS7rbPNRxDWD9spjo0wYj05pLRSQTDf38jNqSANrdYy5hNeVxpGR8Mmds5ox_zWns0YvsNq3evZL_3OB_AOCEjQU</recordid><startdate>202401</startdate><enddate>202401</enddate><creator>Batra, Vandana</creator><creator>Gikandi, Ajami</creator><creator>Pawel, Bruce</creator><creator>Martinez, Daniel</creator><creator>Granger, M Meaghan</creator><creator>Marachelian, Araz</creator><creator>Park, Julie R</creator><creator>Maris, John M</creator><creator>Vo, Kieuhoa T</creator><creator>Matthay, Katherine K</creator><creator>DuBois, Steven G</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9556-106X</orcidid><orcidid>https://orcid.org/0000-0002-0146-2499</orcidid><orcidid>https://orcid.org/0000-0003-3857-4782</orcidid><orcidid>https://orcid.org/0000-0002-8088-7929</orcidid><orcidid>https://orcid.org/0000-0002-9281-7485</orcidid><orcidid>https://orcid.org/0000-0003-0882-738X</orcidid></search><sort><creationdate>202401</creationdate><title>Norepinephrine transporter and vesicular monoamine transporter 2 tumor expression as a predictor of response to 131 I-MIBG in patients with relapsed/refractory neuroblastoma</title><author>Batra, Vandana ; Gikandi, Ajami ; Pawel, Bruce ; Martinez, Daniel ; Granger, M Meaghan ; Marachelian, Araz ; Park, Julie R ; Maris, John M ; Vo, Kieuhoa T ; Matthay, Katherine K ; DuBois, Steven G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c906-74b660fd4db721658d88c158846177ae222376711634209cd2b99fc2484bdf853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>3-Iodobenzylguanidine - therapeutic use</topic><topic>Chronic Disease</topic><topic>Humans</topic><topic>N-Myc Proto-Oncogene Protein</topic><topic>Neoplasm Recurrence, Local - drug therapy</topic><topic>Neuroblastoma - drug therapy</topic><topic>Norepinephrine Plasma Membrane Transport Proteins - metabolism</topic><topic>Radiopharmaceuticals</topic><topic>Vesicular Monoamine Transport Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Batra, Vandana</creatorcontrib><creatorcontrib>Gikandi, Ajami</creatorcontrib><creatorcontrib>Pawel, Bruce</creatorcontrib><creatorcontrib>Martinez, Daniel</creatorcontrib><creatorcontrib>Granger, M Meaghan</creatorcontrib><creatorcontrib>Marachelian, Araz</creatorcontrib><creatorcontrib>Park, Julie R</creatorcontrib><creatorcontrib>Maris, John M</creatorcontrib><creatorcontrib>Vo, Kieuhoa T</creatorcontrib><creatorcontrib>Matthay, Katherine K</creatorcontrib><creatorcontrib>DuBois, Steven G</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Pediatric blood & cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Batra, Vandana</au><au>Gikandi, Ajami</au><au>Pawel, Bruce</au><au>Martinez, Daniel</au><au>Granger, M Meaghan</au><au>Marachelian, Araz</au><au>Park, Julie R</au><au>Maris, John M</au><au>Vo, Kieuhoa T</au><au>Matthay, Katherine K</au><au>DuBois, Steven G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Norepinephrine transporter and vesicular monoamine transporter 2 tumor expression as a predictor of response to 131 I-MIBG in patients with relapsed/refractory neuroblastoma</atitle><jtitle>Pediatric blood & cancer</jtitle><addtitle>Pediatr Blood Cancer</addtitle><date>2024-01</date><risdate>2024</risdate><volume>71</volume><issue>1</issue><spage>e30743</spage><pages>e30743-</pages><issn>1545-5009</issn><issn>1545-5017</issn><eissn>1545-5017</eissn><abstract>Prior studies suggest that norepinephrine transporter (NET) and vesicular monoamine transporter 2 (VMAT2) mediate meta-iodobenzylguanidine (MIBG) uptake and retention in neuroblastoma tumors. We evaluated the relationship between NET and VMAT2 tumor expression and clinical response to
I-MIBG therapy in patients with neuroblastoma.
Immunohistochemistry (IHC) was used to evaluate NET and VMAT2 protein expression levels on archival tumor samples (obtained at diagnosis or relapse) from patients with relapsed or refractory neuroblastoma treated with
I-MIBG. A composite protein expression H-score was determined by multiplying a semi-quantitative intensity value (0-3+) by the percentage of tumor cells expressing the protein.
Tumor samples and clinical data were available for 106 patients, of whom 28.3% had partial response (PR) or higher. NET H-score was not significantly associated with response (≥PR), though the percentage of tumor cells expressing NET was lower among responders (median 80% for ≥PR vs. 90% for <PR; p = .0014). VMAT2 H-score was not significantly associated with PR or higher versus less than PR, though patients with PR or higher had lower VMAT2 staining intensity (p = .005). VMAT2 H-score was significantly lower in patients with complete response (median 40 vs. 210 for patients with <complete response; p = .0049). VMAT2 H-scores were significantly higher in ganglioneuroblastoma (vs. neuroblastoma; p = .037), differentiated/poorly differentiated tumors (vs. undifferentiated; p = .0047), and tumors lacking MYCN amplification (vs. MYCN amplified; p = .0011).
Markers of lower NET and VMAT2 protein expression are associated with higher likelihood of response to
I-MIBG therapy in patients with relapsed/refractory neuroblastoma. Increased VMAT2 protein expression is associated with a more differentiated disease phenotype.</abstract><cop>United States</cop><pmid>37885116</pmid><doi>10.1002/pbc.30743</doi><orcidid>https://orcid.org/0000-0001-9556-106X</orcidid><orcidid>https://orcid.org/0000-0002-0146-2499</orcidid><orcidid>https://orcid.org/0000-0003-3857-4782</orcidid><orcidid>https://orcid.org/0000-0002-8088-7929</orcidid><orcidid>https://orcid.org/0000-0002-9281-7485</orcidid><orcidid>https://orcid.org/0000-0003-0882-738X</orcidid></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | 3-Iodobenzylguanidine - therapeutic use Chronic Disease Humans N-Myc Proto-Oncogene Protein Neoplasm Recurrence, Local - drug therapy Neuroblastoma - drug therapy Norepinephrine Plasma Membrane Transport Proteins - metabolism Radiopharmaceuticals Vesicular Monoamine Transport Proteins - metabolism |
| title | Norepinephrine transporter and vesicular monoamine transporter 2 tumor expression as a predictor of response to 131 I-MIBG in patients with relapsed/refractory neuroblastoma |
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