[89Zr]ZrDFO-CR011 PET Correlates with Response to Glycoprotein Nonmetastatic Melanoma B–targeted Therapy in Triple-negative Breast Cancer

Lee, Supum; Cavaliere, Alessandra; Gallezot, Jean‐Dominique; Keler, Tibor; Michelhaugh, Sharon K.; Belitzky, Erika; Liu, Mengmeng; Mulnix, Tim; Bothwell, Alfred L.M.; Li, Fangyong; Phadke, Manali; Mittal, Sandeep; Marquez-Nostra, Bernadette

doi:10.1158/1535-7163.mct-21-0590

Cited by 4 publications

(5 citation statements)

References 32 publications

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“…For all these trials, there are only two main types of OS: soft and solid, as observed in the table. The following active pharmaceutical ingredients (API) are appropriate for OS: topotecan (Tpt) [45], pazopanib (Pzp) [46], placebo (Plb) [47], gemcitabine (Gct) [48], M6620 [49][50], regorafenib (Rgf) [51][52], glembatumumab vedotin (GV) [53][54], lenvatinib [55], etoposide and ifosfamide (EnI) [56], nab-rapamycin (Rpm) [57][58], cyclophosphamide (Cfa) [59], simvastatin (Sim) [60], myeloid growth factor (MGF) [61], nab-paclitaxel [62][63], methotrexate (Mtx) [64], and doxorubicin (Dox) [65]. Besides, the primary tests, such as laboratory biomarker analyses [66] and dose escalation studies [67], were conducted for these successful triumphs.…”

Section: Clinical Advancementmentioning

confidence: 99%

Relationship between Osteosarcoma Therapy and Tumorigenesis, Metastasis, Immune Evasion, and Chemoresistance

Zaidi¹,

Haque²,

Miskon³

2023

Preprint

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There has been no significant efficacy in treatment for osteosarcoma (OS) metastasis after nearly four decades of trials. This motivates us to elucidate OS therapies according to their four bidirectional mutation stages. To refresh the OS therapy status quo, the historical developments and clinical advancements are briefly described. However, the main issue of metastasis remains unresolved, accounting for 90% of pulmonary metastasis deaths. Thus, this metastasis problem is related to immune evasion and chemoresistance that are being induced after long-term treatment by the use of immunotherapy for tumorigenesis. Therefore, it is rationale to discuss the relationship cycles of mutation stages including tumorigenesis, metastasis, immune evasion, and chemoresistance. Even though many combinational and targeted therapies have been developed to intensify these mutation treatments, successful clinical translations with higher cure rates are still rare. Through this review, an in-depth understanding of the bidirectional relationship between the four OS mutation stages and their respective therapies is provided. Herein, we summarise the medicines used to treat tumorigenesis, including COLGALT2 inhibitors, Tra2B, and AGAP1, miR-148a and miR-21-5p EVs, and the lncRNA LIFR-AS1. Following the medicines used to treat metastasis are AXL, miR-135a-5p, mRNA BCL6, TGFβ1, Tim-3, SOCS5, CASC15, KLF3-AS1, PDCD4, ATG5, and Rab22a-NeoF1. Then the medicines used to treat immune evasion are N-cadherin, anti-IL-9, USP12 inhibitor, IgG-4+ B-cells, LAP inhibitor, anti-Wnt2 mAb, anti-αvβ8 integrin, HK2-mediated IκBα, IDO inhibitor with NO, and TGF-βRII with anti-IgG1. Finally, the medicines used to treat chemoresistance are DHFR, FPGS, HSP-90AA1, XCT-790, ATKI, and IGF1. As a result, this contribution is expected to serve as a reference and guide for scientists and clinicians.

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Section: Clinical Advancementmentioning

confidence: 99%

Relationship between Osteosarcoma Therapy and Tumorigenesis, Metastasis, Immune Evasion, and Chemoresistance

Zaidi¹,

Haque²,

Miskon³

2023

Preprint

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“…The cell line MDA-MA-468 was chosen due to its moderate expression of gpNMB; whereas, MDA-MB-231 was selected because it does not express gpNMB and was used as a negative control [18]. The IC50 value for dasatinib was first determined in vitro to select an appropriate dose for the treatment of cells, where the IC50 was determined to be 2.25 μM (Fig S1A).…”

Section: Dasatinib Treatment Upregulates Gpnmb Expression In Mda-mb-4...mentioning

confidence: 99%

“…Positron emission tomography (PET) imaging is a noninvasive imaging modality that has potential to predict which patients are likely to respond to treatment by determining relative expression of therapeutic targets prior to treatment [18][19][20]. ImmunoPET combines the specificity of antibodies with the sensitivity of PET imaging to detect antigen biomarkers.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, PET imaging could be used to monitor how expression of a therapeutic target changes with single agent or combination treatment [14,22]. In previous studies, we developed [ 89 Zr]Zr-DFO-CR011 to image gpNMB in vivo and predict response to CDX-011 therapy in preclinical models of TNBC [18,19].…”

Section: Introductionmentioning

confidence: 99%

“…Dasatinib has been approved for treatment of chronic myeloid leukemia (CML) and is under investigation for other cancers including breast cancer [13]. However, there is a need for prognostic markers to help select patients likely to benefit from combination therapy and to define the timepoint of combination treatment [18].…”

Section: Introductionmentioning

confidence: 99%

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ImmunoPET imaging identifies the optimal timepoint for combination therapy in preclinical models of triple negative breast cancer

Belitzky

Bláha

et al. 2022

Preprint

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Purpose To quantify the degree and identify the timeframe of glycoprotein nonmetastatic melanoma B (gpNMB) upregulation in vivo after treatment with the Src tyrosine kinase inhibitor, dasatinib, by longitudinal PET imaging with the 89Zr-labeled anti-gpNMB antibody ([89Zr]Zr-DFO-CR011). The goal is to identify the timepoint at which to administer the corresponding antibody drug conjugate, CDX-011 following treatment with dasatinib to enhance therapeutic efficacy of sequential targeted treatments using noninvasive imaging to guide therapy. Methods First, TNBC cell lines that either express gpNMB (MDA-MB-468) or do not express gpNMB (MDA-MB-231) were treated with dasatinib in vitro for 48 h followed by western blot analysis to determine differences in gpNMB expression. MDA-MB-468 xenografted mice were treated with dasatinib. Subgroups of mice were euthanized at 0-, 7-, 14-, and 21-days post treatment, and tumors were harvested for western blot analysis of gpNMB. In a different cohort of MDA-MB-468 xenograft models, longitudinal PET imaging with [89Zr]Zr-DFO-CR011 was performed before treatment at 0- (baseline), and at 14- and 28-days after treatment with dasatinib, CDX-011, or their combination, to determine changes in gpNMB expression in vivo relative to baseline. As a gpNMB-negative control, MDA-MB-231 xenograft models were imaged at 21 days after treatment with dasatinib, combination of CDX-011 and dasatinib, and vehicle control. Results Western blot analysis of MDA-MB-468 cell and tumor lysates validated that dasatinib increased expression of gpNMB in vitro and in vivo at 14 days post treatment initiation. In PET imaging studies of different cohorts of MDA-MB-468 xenografted mice, [89Zr]Zr-DFO-CR011 uptake in tumors (SUVmean = 3.2 ± 0.3) was greatest at 14 days after treatment with dasatinib (SUVmean = 4.9 ± 0.6) or combination of dasatinib and CDX-011 (SUVmean= 4.6 ± 0.2) compared with that at baseline (SUVmean = 3.2 ± 0.3). The highest tumor regression after treatment was observed in the combination-treated group with a percent change in tumor volume relative to baseline (%CTV) of -54 ± 13 compared with the vehicle control-treated group (%CTV = +102 ± 27), CDX-011 group (%CTV = -25 ± 9.8), and dasatinib group (%CTV = -23 ± 11). In contrast, the PET imaging of MDA-MB-231 xenografted mice indicated no significant difference in the tumor uptake of [89Zr]Zr-DFO-CR011 between treated (dasatinib alone or in combination with CDX-011) and vehicle-control groups. Conclusions Dasatinib upregulated gpNMB expression in gpNMB-positive MDA-MB-468 xenografted tumors at 14 days post treatment initiation, which can be quantified by PET imaging with [89Zr]Zr-DFO-CR011. Furthermore, combination therapy with dasatinib and CDX-011 appears to be a promising therapeutic strategy for TNBC and warrants further investigation.

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Non-specific irreversible 89Zr-mAb uptake in tumours: evidence from biopsy-proven target-negative tumours using 89Zr-immuno-PET

Wijngaarden,

Jauw,

Zwezerijnen

et al. 2024

EJNMMI Res

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Background Distribution of mAbs into tumour tissue may occur via different processes contributing differently to the 89Zr-mAb uptake on PET. Target-specific binding in tumours is of main interest; however, non-specific irreversible uptake may also be present, which influences quantification. The aim was to investigate the presence of non-specific irreversible uptake in tumour tissue using Patlak linearization on 89Zr-immuno-PET data of biopsy-proven target-negative tumours. Data of two studies, including target status obtained from biopsies, were retrospectively analysed, and Patlak linearization provided the net rate of irreversible uptake (Ki). Results Two tumours were classified as CD20-negative and two as CD20-positive. Four tumours were classified as CEA-negative and nine as CEA-positive. Ki values of CD20-negative (0.43 µL/g/h and 0.92 µL/g/h) and CEA-negative tumours (mdn = 1.97 µL/g/h, interquartile range (IQR) = 1.50–2.39) were higher than zero. Median Ki values of target-negative tumours were lower than CD20-positive (1.87 µL/g/h and 1.90 µL/g/h) and CEA-positive tumours (mdn = 2.77 µL/g/h, IQR = 2.11–3.65). Conclusion Biopsy-proven target-negative tumours showed irreversible uptake of 89Zr-mAbs measured in vivo using 89Zr-immuno-PET data, which suggests the presence of non-specific irreversible uptake in tumours. Consequently, for 89Zr-immuno-PET, even if the target is absent, a tumour-to-plasma ratio always increases over time.

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[89Zr]ZrDFO-CR011 PET Correlates with Response to Glycoprotein Nonmetastatic Melanoma B–targeted Therapy in Triple-negative Breast Cancer

Cited by 4 publications

References 32 publications

Relationship between Osteosarcoma Therapy and Tumorigenesis, Metastasis, Immune Evasion, and Chemoresistance

Relationship between Osteosarcoma Therapy and Tumorigenesis, Metastasis, Immune Evasion, and Chemoresistance

ImmunoPET imaging identifies the optimal timepoint for combination therapy in preclinical models of triple negative breast cancer

Non-specific irreversible 89Zr-mAb uptake in tumours: evidence from biopsy-proven target-negative tumours using 89Zr-immuno-PET

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