Optical Imaging of Disseminated Leukemia Models in Mice with Near-Infrared Probe Conjugated to a Monoclonal Antibody

Pesnel, Sabrina; Pillon, Arnaud; Créancier, Laurent; Lerondel, Stéphanie; Pape, Alain Le; Récher, Christian; Demur, Cécile; Guilbaud, Nicolas; Kruczynski, Anna

doi:10.1371/journal.pone.0030690

Cited by 7 publications

(5 citation statements)

References 20 publications

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“…Similar observations have been reported by other groups examining different models of solid tumors and leukemia [21]. That a convenient, reliable and sensitive tracking of myeloma cells is indeed valuable with whole body imaging techniques in living animals has been demonstrated by various groups [22,23].…”

Section: Discussionsupporting

confidence: 82%

Intratibial Injection of Human Multiple Myeloma Cells in NOD/SCID IL-2Rγ(Null) Mice Mimics Human Myeloma and Serves as a Valuable Tool for the Development of Anticancer Strategies

Schueler

Wider

Klingner³

et al. 2013

PLoS ONE

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BackgroundWe systematically analyzed multiple myeloma (MM) cell lines and patient bone marrow cells for their engraftment capacity in immunodeficient mice and validated the response of the resulting xenografts to antimyeloma agents.Design and MethodsUsing flow cytometry and near infrared fluorescence in-vivo-imaging, growth kinetics of MM cell lines L363 and RPMI8226 and patient bone marrow cells were investigated with use of a murine subcutaneous bone implant, intratibial and intravenous approach in NOD/SCID, NOD/SCID treated with CD122 antibody and NOD/SCID IL-2Rγ(null) mice (NSG).ResultsMyeloma growth was significantly increased in the absence of natural killer cell activity (NSG or αCD122-treated NOD/SCID). Comparison of NSG and αCD122-treated NOD/SCID revealed enhanced growth kinetics in the former, especially with respect to metastatic tumor sites which were exclusively observed therein. In NSG, MM cells were more tumorigenic when injected intratibially than intravenously. In NOD/SCID in contrast, the use of juvenile long bone implants was superior to intratibial or intravenous cancer cell injection. Using the intratibial NSG model, mice developed typical disease symptoms exclusively when implanted with human MM cell lines or patient-derived bone marrow cells, but not with healthy bone marrow cells nor in mock-injected animals. Bortezomib and dexamethasone delayed myeloma progression in L363- as well as patient-derived MM cell bearing NSG. Antitumor activity could be quantified via flow cytometry and in vivo imaging analyses.ConclusionsOur results suggest that the intratibial NSG MM model mimics the clinical situation of the disseminated disease and serves as a valuable tool in the development of novel anticancer strategies.

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Section: Discussionsupporting

confidence: 82%

Intratibial Injection of Human Multiple Myeloma Cells in NOD/SCID IL-2Rγ(Null) Mice Mimics Human Myeloma and Serves as a Valuable Tool for the Development of Anticancer Strategies

Schueler

Wider

Klingner³

et al. 2013

PLoS ONE

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“…However, the use of PET scanners in biosafety level 3 animal facilities is limited and we wanted to prove this approach was successful using fluorescent imaging and a well-established anatomical site of infection before embarking on these resource intensive experiments. Previous work in mice has shown that signal from fluorescently labeled probes correlates well to signal from identical probes imaged using bioluminescence imaging (BLI) or PET (31,34). The promising results reported here have given confidence in adopting this antibody-based fluorescent probe system to PET imaging.…”

Section: Discussionsupporting

confidence: 58%

“…Therefore, we hypothesize that the probe was interfering with the establishment and spread of infection in those macaques given probe 1-or 2-days p.i. Similar interference with the biological process under study has been seen with other antibody probes (34). This underscores the need to carefully choose antibodies to be developed as probes, as those that interfere with the natural progression of infections will be less useful in studying pathogenesis.…”

Section: Discussionmentioning

confidence: 72%

“…Antibodybased probes can be labeled with radioisotopes detected using positron emission tomography (PET) or with fluorescent dyes detected through optical imaging. These techniques have been used for many years to image cancerous cells and biological processes, but only more recently have they been applied to study pathogens (25)(26)(27)(28)(29)(30)(31)(32)(33)(34). Studies of fungi, bacteria, and even parasites have been undertaken using pathogen specific antibodies as probes to study the distribution and kinetics of infection (35)(36)(37)(38)(39).…”

Section: Introductionmentioning

confidence: 99%

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Development of an In Vivo Probe to Track SARS-CoV-2 Infection in Rhesus Macaques

et al. 2021

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Infection with the novel coronavirus, SARS-CoV-2, results in pneumonia and other respiratory symptoms as well as pathologies at diverse anatomical sites. An outstanding question is whether these diverse pathologies are due to replication of the virus in these anatomical compartments and how and when the virus reaches those sites. To answer these outstanding questions and study the spatiotemporal dynamics of SARS-CoV-2 infection a method for tracking viral spread in vivo is needed. We developed a novel, fluorescently labeled, antibody-based in vivo probe system using the anti-spike monoclonal antibody CR3022 and demonstrated that it could successfully identify sites of SARS-CoV-2 infection in a rhesus macaque model of COVID-19. Our results showed that the fluorescent signal from our antibody-based probe could differentiate whole lungs of macaques infected for 9 days from those infected for 2 or 3 days. Additionally, the probe signal corroborated the frequency and density of infected cells in individual tissue blocks from infected macaques. These results provide proof of concept for the use of in vivo antibody-based probes to study SARS-CoV-2 infection dynamics in rhesus macaques.

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“…35 At no point in the present study did we experience any cellular deviations or changes in model pathogenesis in response to the pool of mAbs used. It was particularly encouraging that this imaging strategy gave better contrast than reporter gene imaging with GFP or bioluminescence in the time-domain configuration and could be used in multiple models of AML and in therapeutic settings.…”

Section: Discussionmentioning

confidence: 70%

Multiplexed mAbs: a new strategy in preclinical time-domain imaging of acute myeloid leukemia

McCormack

Mujić

Osdal

et al. 2013

Blood

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Key Points• Multiplexing antibodies against common human epitopes all labeled with the same fluorophore facilitates optical imaging of heterogenous AML.• Multiplexing fluorescently labeled monoclonal antibodies permits optical imaging of primary patient xenograft pathology/therapy response.Antibodies play a fundamental role in diagnostic immunophenotyping of leukemias and in cell-targeting therapy. However, this versatility is not reflected in imaging diagnostics. In the present study, we labeled anti-human mAbs monochromatically against selected human myeloid markers expressed on acute myeloid leukemia (AML) cells, all with the same near-infrared fluorochrome. In a novel "multiplexing" strategy, we then combined these mAbs to overcome the limiting target-to-background ratio to image multiple xenografts of AML. Time-domain imaging was used to discriminate autofluorescence from the distinct fluorophore-conjugated antibodies. Imaging with multiplexed mAbs demonstrated superior imaging of AML to green fluorescent protein or bioluminescence and permitted evaluation of therapeutic efficacy with the standard combination of anthracycline and cytarabine in primary patient xenografts. Multiplexing mAbs against CD11b and CD11c provided surrogate imaging biomarkers of differentiation therapy in an acute promyelocytic leukemia model treated with all-trans retinoic acid combined with the histone-deacetylase inhibitor valproic acid. We present herein an optimizedapplication of multiplexed immunolabeling in vivo for optical imaging of AML cellxenografts that provides reproducible, highly accurate disease staging and monitoring of therapeutic effects. (Blood. 2013;121(7):e34-e42) IntroductionDespite modern advances in therapeutics and improvement in the diagnosis of acute myeloid leukemia (AML) subtypes, the majority of patients die from their disease. 1,2 Thus, in the absence of definitive in vitro models of human AML and failure of significant numbers of new drugs late in clinical trials, 3,4 it is essential that murine AML models are further developed to exploit more specific, targeted therapeutics. Although preclinical development of therapeutics has previously exploited genetic and syngeneic models of AML, 5,6 subcutaneous xenografting of human cell lines in immunodeficient mice has been a popular screening tool. 7 However, the ease of measuring therapeutic efficacy with simple caliper measurements in subcutaneous tumors is offset by the recognition that these models do not typify clinical disease. 8,9 True evaluation of therapeutic potential in this disease necessitates preclinical screening in multiple, systemic, or orthotopic xenograft models of AML, increasingly with primary patient cells that reflect the heterogeneity of the disease. 10 To facilitate the use of humanized orthotopic AML models in therapeutic settings, investigators have increasingly turned to noninvasive preclinical imaging techniques to define efficacy. 11 Optical imaging of reporter gene expression 12,13 is the preferred modality owing to low cost an...

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Optical Imaging of Disseminated Leukemia Models in Mice with Near-Infrared Probe Conjugated to a Monoclonal Antibody

Cited by 7 publications

References 20 publications

Intratibial Injection of Human Multiple Myeloma Cells in NOD/SCID IL-2Rγ(Null) Mice Mimics Human Myeloma and Serves as a Valuable Tool for the Development of Anticancer Strategies

Intratibial Injection of Human Multiple Myeloma Cells in NOD/SCID IL-2Rγ(Null) Mice Mimics Human Myeloma and Serves as a Valuable Tool for the Development of Anticancer Strategies

Development of an In Vivo Probe to Track SARS-CoV-2 Infection in Rhesus Macaques

Multiplexed mAbs: a new strategy in preclinical time-domain imaging of acute myeloid leukemia

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