Multimodal Bioluminescent and Positronic-emission Tomography/Computational Tomography Imaging of Multiple Myeloma Bone Marrow Xenografts in NOG Mice

Gastelum, Gilberto; Chang, Eric Y.; Shackleford, David M.; Bernthal, Nicholas M.; Kraut, Jeffery; Francis, Kevin P.; Smutko, Victoria; Frost, Patrick

doi:10.3791/58056

Cited by 3 publications

(5 citation statements)

References 16 publications

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“…RPMI-8226-Luc human multiple myeloma cells were successfully engrafted at the left femur and pelvis or lower lumbar bone of test animals, as demonstrated by intense bioluminescence from these sites post injection (Figure B). The pattern of RPMI-8226-Luc human multiple myeloma cell engraftment in NSG/BLT mice was highly consistent with the well-established model using NOG immunodeficient mice. , …”

Section: Resultssupporting

confidence: 83%

“…It has been reported that the human multiple myeloma cells (RPMI-8226-Luc) require several weeks for the orthotropic grafting after injection in mice. 39 There was a bioluminescent signal near the tail vein injection site until 4 weeks suggesting the presence of RPMI-8226-Luc cells. However, this bioluminescent signal near the tail vein injection site disappeared at 5 weeks, while a new bioluminescent signal was detected at the cervical/ thoracic bone (arrow in Figure 7C).…”

Section: ■ Results and Discussionmentioning

confidence: 97%

“…After 7 days, 100 μL of 50 μM OFS-1 was injected retro-orbitally, and the animals were examined by in vivo fluorescence imaging at 3, 4, and 5 weeks after RPMI-8226-Luc multiple myeloma cell injection (Figure C). It has been reported that the human multiple myeloma cells (RPMI-8226-Luc) require several weeks for the orthotropic grafting after injection in mice . There was a bioluminescent signal near the tail vein injection site until 4 weeks suggesting the presence of RPMI-8226-Luc cells.…”

Section: Resultsmentioning

confidence: 99%

“…The pattern of RPMI-8226-Luc human multiple myeloma cell engraftment in NSG/BLT mice was highly consistent with the well-established model using NOG immunodeficient mice. 39,40 After 7 days, 100 μL of 50 μM OFS-1 was injected retroorbitally, and the animals were examined by in vivo fluorescence imaging at 3, 4, and 5 weeks after RPMI-8226-Luc multiple myeloma cell injection (Figure 7C). It has been reported that the human multiple myeloma cells (RPMI-8226-Luc) require several weeks for the orthotropic grafting after injection in mice.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Design and Synthesis of Cathepsin-K-Activated Osteoadsorptive Fluorogenic Sentinel (OFS) Probes for Detecting Early Osteoclastic Bone Resorption in a Multiple Myeloma Mouse Model

Richard

Morinaga²,

Zheng

et al. 2021

Bioconjugate Chem.

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We describe the design and synthesis of OFS-1, an Osteoadsorptive Fluorogenic Sentinel imaging probe that is adsorbed by hydroxyapatite (HAp) and bone mineral surfaces, where it generates an external fluorescent signal in response to osteoclastsecreted cathepsin K (Ctsk). The probe consists of a bone-anchoring bisphosphonate moiety connected to a Forster resonance energy transfer (FRET) internally quenched fluorescent (IQF) dye pair, linked by a Ctsk peptide substrate, GHPGGPQG. Key structural features contributing to the effectiveness of OFS-1 were defined by structure−activity relationship (SAR) and modeling studies comparing OFS-1 with two cognates, OFS-2 and OFS-3. In solution or when preadsorbed on HAp, OFS-1 exhibited strong fluorescence when exposed to Ctsk (2.5−20 nM). Time-lapse photomicrographs obtained after seeding human osteoclasts onto HAp-coated well plates containing preadsorbed OFS-1 revealed bright fluorescence at the periphery of resorbing cells. OFS-1 administered systemically detected early osteolysis colocalized with orthotopic engraftment of RPMI-8226-Luc human multiple myeloma cells at a metastatic skeletal site in a humanized mouse model. OFS-1 is thus a promising new imaging tool for detecting abnormal bone resorption.

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Section: Resultssupporting

confidence: 83%

Section: ■ Results and Discussionmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Design and Synthesis of Cathepsin-K-Activated Osteoadsorptive Fluorogenic Sentinel (OFS) Probes for Detecting Early Osteoclastic Bone Resorption in a Multiple Myeloma Mouse Model

Richard

Morinaga²,

Zheng

et al. 2021

Bioconjugate Chem.

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“…All cell lines have MM surface markers, secrete immunoglobulin or light chains, and are Epstein-Barr virus-negative ( 24 – 27 ). The luciferase-transfected MM cell line, RPMI-8226 (8226/Luc) was provided by Dr. Patrick Frost, UCLA ( 28 ). The melphalan-resistant MM cell line 8226/LR5 and bortezomib-resistant line, 8226/B25, were gifted by Dr. Kenneth Shain of the Moffitt Cancer Center ( 29 , 30 ).…”

Section: Methodsmentioning

confidence: 99%

Extracellular vesicles derived from immortalized human natural killer cell line NK3.3 as a novel therapeutic for multiple myeloma

Matchett,

Kornbluth

2023

Front. Immunol.

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IntroductionOver the last decade, there have been many advancements in the therapeutic treatment of multiple myeloma (MM), including the use of natural killer (NK) cells. However, despite promising results from clinical trials, there are concerns over the use of NK cell-based therapy. Cells often undergo growth arrest, limiting their experimental utility; donor cells are extremely heterogeneous, resulting in content variability; and patients receiving allogeneic cells are at risk for graft-versus-host disease and/or cytokine release syndrome. Extracellular vesicles (EVs) have emerged as a new natural therapeutic tool. EVs are known to carry cargo derived from the parent cell from which they originate. NK cells play an important role in the innate immune system, targeting and killing tumor cells. This has led many researchers to isolate EVs from NK cells for their cytotoxic potential.MethodsIn this study, we isolated EVs from the NK cell line, NK3.3, which was derived from the peripheral blood of a healthy donor. Currently, it is the only normal human NK cell line reported with all the functional characteristics of healthy NK cells. To address the issue of growth arrest, we immortalized NK3.3 cells with lentivirus encoding the catalytic subunit of human telomerase htert (NK3.3-LTV). EVs from these cells were isolated using a modified polyethylene glycol (PEG)-acetate precipitation protocol to simplify processing and increase EV yield.Results and conclusionsWe demonstrated that NK3.3-LTV EVs target both sensitive and drug-resistant MM cell lines as well as primary patient MM cells in vitro, decreasing proliferation and inducing apoptotic cell death as well as or better than EVs from non-immortalized cells with no toxicity towards normal cells. This study is the first step towards developing an immunotherapeutic product designed to treat patients with relapsed/refractory MM.

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AcidoCEST MRI Evaluates the Bone Microenvironment in Multiple Myeloma

et al. 2021

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Multimodal Bioluminescent and Positronic-emission Tomography/Computational Tomography Imaging of Multiple Myeloma Bone Marrow Xenografts in NOG Mice

Cited by 3 publications

References 16 publications

Design and Synthesis of Cathepsin-K-Activated Osteoadsorptive Fluorogenic Sentinel (OFS) Probes for Detecting Early Osteoclastic Bone Resorption in a Multiple Myeloma Mouse Model

Design and Synthesis of Cathepsin-K-Activated Osteoadsorptive Fluorogenic Sentinel (OFS) Probes for Detecting Early Osteoclastic Bone Resorption in a Multiple Myeloma Mouse Model

Extracellular vesicles derived from immortalized human natural killer cell line NK3.3 as a novel therapeutic for multiple myeloma

AcidoCEST MRI Evaluates the Bone Microenvironment in Multiple Myeloma

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