First Demonstration of Leukemia Imaging with the Proliferation Marker <sup>18</sup>F-Fluorodeoxythymidine

Buck, Andreas K.; Bommer, Martin; Juweid, Malik E.; Glatting, Gerhard; Stilgenbauer, Stephan; Mottaghy, Felix M.; Schulz, Melanie; Kull, Thomas; Bunjes, Donald; Möller, Peter; Döhner, Hartmut; Reske, Sven N.

doi:10.2967/jnumed.108.055335

Cited by 66 publications

(60 citation statements)

References 26 publications

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“…20 This finding could be clinically relevant since EM-AML may respond differently to standard chemotherapy. By applying 18 F-FDG-PET/CT in our study, we were able to detect EM-AML in patients with de novo AML, as well as AML relapsed after chemotherapy and allogeneic HSCT.…”

Section: Resultsmentioning

confidence: 88%

18F-FDG-PET/CT for detection of extramedullary acute myeloid leukemia

Stölzel

Röllig²,

Radke³

et al. 2011

Haematologica

112

101

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Section: Resultsmentioning

confidence: 88%

18F-FDG-PET/CT for detection of extramedullary acute myeloid leukemia

Stölzel

Röllig²,

Radke³

et al. 2011

Haematologica

112

101

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“…Therefore, radiopharmaceuticals directly related to cell proliferation, such as 3′-deoxy-3′-[ 18 [2]. Prior studies have established that [ 18 F]FLT uptake correlates with Ki-67 immunostaining proliferation assay, in breast cancer [3], lung cancer [4], and leukemia [5], and with S phase fraction in lung tumors as measured by flow cytometry [6]. Tumor imaging with [ 18 F]FLT PET has been shown to be generally specific in cancer diagnosis [7].…”

Section: Introductionmentioning

confidence: 99%

Increase of [18F]FLT Tumor Uptake In Vivo Mediated by FdUrd: Toward Improving Cell Proliferation Positron Emission Tomography

et al. 2010

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“…There are very few imaging biomarkers approved for clinical use; however, AML imaging with 18 F-FLT 37,38 advocates a PET/CT-based multiplexed mAb imaging strategy with appropriate isotopic labeling of humanized mAbs. Such a strategy would necessitate extensive evaluation to determine clinically meaningful benefit over current flow cytometry-and PCR-based techniques.…”

mentioning

confidence: 99%

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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First Demonstration of Leukemia Imaging with the Proliferation Marker ¹⁸F-Fluorodeoxythymidine

Cited by 66 publications

References 26 publications

18F-FDG-PET/CT for detection of extramedullary acute myeloid leukemia

18F-FDG-PET/CT for detection of extramedullary acute myeloid leukemia

Increase of [18F]FLT Tumor Uptake In Vivo Mediated by FdUrd: Toward Improving Cell Proliferation Positron Emission Tomography

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

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First Demonstration of Leukemia Imaging with the Proliferation Marker 18F-Fluorodeoxythymidine

Cited by 66 publications

References 26 publications

18F-FDG-PET/CT for detection of extramedullary acute myeloid leukemia

18F-FDG-PET/CT for detection of extramedullary acute myeloid leukemia

Increase of [18F]FLT Tumor Uptake In Vivo Mediated by FdUrd: Toward Improving Cell Proliferation Positron Emission Tomography

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

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First Demonstration of Leukemia Imaging with the Proliferation Marker ¹⁸F-Fluorodeoxythymidine