Upregulated myocardial CXCR4-expression after myocardial infarction assessed by simultaneous GA-68 pentixafor PET/MRI

Rischpler, Christoph; Nekolla, Stephan G.; Kossmann, Hans; Dirschinger, Ralf J.; Schottelius, Margret; Hyafil, Fabien; Wester, Hans‐Jürgen; Laugwitz, Karl Ludwig; Schwaiger, Markus

doi:10.1007/s12350-015-0347-5

Cited by 42 publications

(27 citation statements)

References 6 publications

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“…Proof-of-concept visualization with this tracer could be demonstrated not only for several different hematologic and other neoplasms-including leukemia, lymphoma, multiple myeloma, adrenocortical carcinoma, and small cell lung cancer (Fig. 2) (72-77)-but also for other solid tumors and disease conditionssuch as splenosis, stroke, atherosclerosis, and myocardial infarction (78)(79)(80)(81)(82)(83)(84).…”

Section: Cxcr4 Receptor Imaging and Cxcr4-directed Radionuclide Therapymentioning

confidence: 95%

CXCR4 Ligands: The Next Big Hit?

et al. 2017

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Section: Cxcr4 Receptor Imaging and Cxcr4-directed Radionuclide Therapymentioning

confidence: 95%

CXCR4 Ligands: The Next Big Hit?

et al. 2017

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“…Besides its successful application in patients with lymphoma 12, multiple myeloma 13, AML 14, SCLC 15, glioblastoma 16 or other solid tumors 17 such as non-small cell lung cancer 18 or adrenocortical cancer 19, [ 68 Ga]pentixafor-PET has recently been shown to be a valuable tool for the in vivo detection of inflammatory processes e.g. after myocardial infarction 20-22 or ischemic stroke 23 as well as in atherosclerosis 24 or urinary tract infection 25. The possibility to non-invasively quantify CXCR4 expression using [ 68 Ga]pentixafor-PET is anticipated to further strengthen the emerging role of CXCR4 as a diagnostic marker, matching its already established importance as a therapeutic target.…”

Section: Introductionmentioning

confidence: 99%

[¹⁷⁷Lu]pentixather: Comprehensive Preclinical Characterization of a First CXCR4-directed Endoradiotherapeutic Agent

Schottelius¹,

Osl²,

Poschenrieder³

et al. 2017

Theranostics

107

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Purpose: Based on the clinical relevance of the chemokine receptor 4 (CXCR4) as a molecular target in cancer and on the success of [68Ga]pentixafor as an imaging probe for high-contrast visualization of CXCR4-expression, the spectrum of clinical CXCR4-targeting was expanded towards peptide receptor radionuclide therapy (PRRT) by the development of [177Lu]pentixather.Experimental design: CXCR4 affinity, binding specificity, hCXCR4 selectivity and internalization efficiency of [177Lu]pentixather were evaluated using different human and murine cancer cell lines. Biodistribution studies (1, 6, 48, 96h and 7d p.i.) and in vivo metabolite analyses were performed using Daudi-lymphoma bearing SCID mice. Extrapolated organ doses were cross-validated with human dosimetry (pre-therapeutic and during [177Lu]pentixather PRRT) in a patient with multiple myeloma (MM).Results: [177Lu]pentixather binds with high affinity, specificity and selectivity to hCXCR4 and shows excellent in vivo stability. Consequently, and supported by >96% plasma protein binding and a logP=-1.76, delaying whole-body clearance of [177Lu]pentixather, tumor accumulation was high and persistent, both in the Daudi model and the MM patient. Tumor/background ratios (7d p.i.) in mice were 499±202, 33±7, 4.0±0.8 and 116±22 for blood, intestine, kidney and muscle, respectively. In the patient, high tumor/kidney and tumor/liver dose ratios of 3.1 and 6.4 were observed during [177Lu]pentixather PRRT (7.8 GBq), with the kidneys being the dose-limiting organs.Conclusions: [177Lu]pentixather shows excellent in vivo CXCR4-targeting characteristics and a suitable pharmacokinetic profile, leading to high tumor uptake and retention and thus high radiation doses to tumor tissue during PRRT, suggesting high clinical potential of this [68Ga]pentixafor/[177Lu]pentixather based CXCR4-targeted theranostic concept.

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“…In cases of specific tracers against certain imaging targets (like inflammatory cells) or poor myocardium to background ratio, polar plots cannot be created using these methods. In this respect, it is important to appreciate that some of the most promising applications of cardiac PET/MRI involve the imaging of myocardial inflammation, which currently is either performed using FDG with dietary suppression of myocardial glucose uptake [17] or with specific tracers against inflammatory cells that do not show significant uptake in myocardial cells [18]. In both cases it is not possible to create valid polar plots of the left ventricular tracer uptake using standard software.…”

Section: Discussionmentioning

confidence: 99%

Integrated Assessment of Cardiac PET/MRI: Co-Registered PET and MRI Polar Plots by Mutual MR-Based Segmentation of the Left Ventricular Myocardium

Nensa¹,

Poeppel²,

Tezgah³

et al. 2017

WJCD

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Background: In the present study, we sought to describe a procedure for the creation of co-registered positron emission tomography (PET) and magnetic resonance imaging (MRI) polar plots of cardiac PET/MRI examinations, validate the resulting plots against available standard methods in patients with myocardial infarction and provide examples that demonstrate the advantage of the novel approach over existing standards. Methods: Co-registered LGE and PET short-axis images were transformed into polar maps based on a radial sampling pattern. LGE was automatically detected using an automated thresholding algorithm (ATA). In 20 PET/MRI examinations in patients with acute myocardial infarction, agreement between manual LGE assessment and the ATA classification was calculated. Also agreement between MRI-segmentation based PET polar plots and standard PET polar plots (created with the Corridor4DM software package) was assessed. Results: No statistically significant difference in infarct sizes between manual and ATA segmentation was found (p = 0.12). Both methods were highly correlated (Pearson's r = 0.96, p < 0.01). Bland-Altman analysis revealed lower and upper limits of agreement of −4.7 g and 3.6 g. Agreement between MRI-segmentation based PET polar plots and standard PET polar plots was very high (mean kappa of 0.91 ± 0.10; p < 0.01 in all cases). In three additional patients with myocardial inflammation, the software successfully created polar plots that demonstrate How to cite this paper: Nensa, F., Poeppel, T.D., Tezgah, E., Heusch, P., Nassenstein, K., Forsting, M., Bockisch, A., Erbel, R. and 92the location and extent of pathologic tracer uptake in the left ventricular myocardium. Conclusion: A straightforward software approach for the creation of co-registered PET and MRI polar plots was described and successfully demonstrated in PET/MRI studies of myocardial infarction and inflammation.

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Upregulated myocardial CXCR4-expression after myocardial infarction assessed by simultaneous GA-68 pentixafor PET/MRI

Cited by 42 publications

References 6 publications

CXCR4 Ligands: The Next Big Hit?

CXCR4 Ligands: The Next Big Hit?

[¹⁷⁷Lu]pentixather: Comprehensive Preclinical Characterization of a First CXCR4-directed Endoradiotherapeutic Agent

Integrated Assessment of Cardiac PET/MRI: Co-Registered PET and MRI Polar Plots by Mutual MR-Based Segmentation of the Left Ventricular Myocardium

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Upregulated myocardial CXCR4-expression after myocardial infarction assessed by simultaneous GA-68 pentixafor PET/MRI

Cited by 42 publications

References 6 publications

CXCR4 Ligands: The Next Big Hit?

CXCR4 Ligands: The Next Big Hit?

[177Lu]pentixather: Comprehensive Preclinical Characterization of a First CXCR4-directed Endoradiotherapeutic Agent

Integrated Assessment of Cardiac PET/MRI: Co-Registered PET and MRI Polar Plots by Mutual MR-Based Segmentation of the Left Ventricular Myocardium

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Product

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[¹⁷⁷Lu]pentixather: Comprehensive Preclinical Characterization of a First CXCR4-directed Endoradiotherapeutic Agent