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01-02-2022 | Molecular Imaging | Brief Article

Examining the Feasibility of Quantifying Receptor Availability Using Cross-Modality Paired-Agent Imaging

Authors: Boyu Meng, Negar Sadeghipour, Margaret R. Folaron, Rendall R. Strawbridge, Kimberley S. Samkoe, Kenneth M. Tichauer, Scott C. Davis

Published in: Molecular Imaging and Biology | Issue 1/2022

Abstract

Purpose

The ability to noninvasively quantify receptor availability (RA) in solid tumors is an aspirational goal of molecular imaging, often challenged by the influence of non-specific accumulation of the contrast agent. Paired-agent imaging (PAI) techniques aim to compensate for this effect by imaging the kinetics of a targeted agent and an untargeted isotype, often simultaneously, and comparing the kinetics of the two agents to estimate RA. This is usually accomplished using two spectrally distinct fluorescent agents, limiting the technique to superficial tissues and/or preclinical applications. Applying the approach in humans using conventional imaging modalities is generally infeasible since most modalities are unable to routinely image multiple agents simultaneously. We examine the ability of PAI to be implemented in a cross-modality paradigm, in which the targeted and untargeted agent kinetics are imaged with different modalities and used to recover receptor availability.

Procedures

Eighteen mice bearing orthotopic brain tumors were administered a solution containing three contrast agents: (1) a fluorescent agent targeted to epidermal growth factor receptor (EGFR), (2) an untargeted fluorescent isotype, and (3) a gadolinium-based contrast agent (GBCA) for MRI imaging. The kinetics of all three agents were imaged for 1 h after administration using an MRI-coupled fluorescence tomography system. Paired-agent receptor availability was computed using (1) the conventional all-optical approach using the targeted and untargeted optical agent images and (2) the cross-modality approach using the targeted optical and untargeted MRI-GBCA images. Receptor availability estimates between the two methods were compared.

Results

Receptor availability values using the cross-modality approach were highly correlated to the conventional, single-modality approach (r = 0.94; p < 0.00001).

Conclusion

These results suggest that cross-modality paired-agent imaging for quantifying receptor availability is feasible. Ultimately, cross-modality paired-agent imaging could facilitate rapid, noninvasive receptor availability quantification in humans using hybrid clinical imaging modalities.

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Dubach JM, Kim E, Yang K, Cuccarese M, Giedt RJ, Meimetis LG, Vinegoni C, Weissleder R (2017) Quantitating drug-target engagement in single cells in vitro and in vivo. Nat Chem Biol 13:168–173. https://doi.org/10.1038/nchembio.2248CrossRefPubMed

Simon GM, Niphakis MJ, Cravatt BF (2013) Determining target engagement in living systems. Nat Chem Biol 9:200–205. https://doi.org/10.1038/nchembio.1211CrossRefPubMedPubMedCentral

Bunnage ME, Chekler ELP, Jones LH (2013) Target validation using chemical probes. Nat Chem Biol 9:195–199. https://doi.org/10.1038/nchembio.1197CrossRefPubMed

Fischman AJ, Alpert NM, Rubin RH (2002) Pharmacokinetic imaging. Clin Pharmacokinet 41:581–602. https://doi.org/10.2165/00003088-200241080-00003CrossRefPubMed

Mammatas LH, Verheul HMW, Hendrikse NH, Yaqub M, Lammertsma AA, Menke-van der Houven van Oordt CW (2015) Molecular imaging of targeted therapies with positron emission tomography: the visualization of personalized cancer care. Cell Oncol 38:49–64. https://doi.org/10.1007/s13402-014-0194-4CrossRef

Matthews PM, Rabiner EA, Passchier J, Gunn RN (2012) Positron emission tomography molecular imaging for drug development. Br J Clin Pharmacol 73:175–186. https://doi.org/10.1111/j.1365-2125.2011.04085.xCrossRefPubMedPubMedCentral

Pressman D, Day ED, Blau M (1957) The use of paired labeling in the determination of tumor-localizing antibodies. Cancer Res 17:845–850PubMed

Tichauer KM, Samkoe KS, Sexton KJ, Hextrum SK, Yang HH, Klubben WS, Gunn JR, Hasan T, Pogue BW (2012) In vivo quantification of tumor receptor binding potential with dual-reporter molecular imaging. Mol Imaging Biol MIB Off Publ Acad Mol Imaging 14:584–592. https://doi.org/10.1007/s11307-011-0534-yCrossRef

Tichauer KM, Wang Y, Pogue BW, Liu JTC (2015) Quantitative in vivo cell-surface receptor imaging in oncology: kinetic modeling & paired-agent principles from nuclear medicine and optical imaging. Phys Med Biol 60:R239–R269. https://doi.org/10.1088/0031-9155/60/14/R239CrossRefPubMedPubMedCentral

10.

Davis SC, Samkoe KS, Tichauer KM, Sexton KJ, Gunn JR, Deharvengt SJ, Hasan T, Pogue BW (2013) Dynamic dual-tracer MRI-guided fluorescence tomography to quantify receptor density in vivo. Proc Natl Acad Sci U S A 110:9025–9030. https://doi.org/10.1073/pnas.1213490110CrossRefPubMedPubMedCentral

11.

Meng B, Folaron MR, Strawbridge RR, Sadeghipour N, Samkoe KS, Tichauer K, Davis SC (2020) Noninvasive quantification of target availability during therapy using paired-agent fluorescence tomography. Theranostics 10:11230–11243. https://doi.org/10.7150/thno.45273CrossRefPubMedPubMedCentral

12.

Samkoe KS, Tichauer KM, Gunn JR, Wells WA, Hasan T, Pogue BW (2014) Quantitative in vivo immunohistochemistry of epidermal growth factor receptor using a receptor concentration imaging approach. Cancer Res 74:7465–7474. https://doi.org/10.1158/0008-5472.CAN-14-0141CrossRefPubMedPubMedCentral

13.

Tichauer KM, Samkoe KS, Klubben WS, Hasan T, Pogue BW (2012) Advantages of a dual-tracer model over reference tissue models for binding potential measurement in tumors. Phys Med Biol 57:6647–6659. https://doi.org/10.1088/0031-9155/57/20/6647CrossRefPubMedPubMedCentral

14.

Wagner A, Mahrholdt H, Holly TA, Elliott MD, Regenfus M, Parker M, Klocke FJ, Bonow RO, Kim RJ, Judd RM (2003) Contrast-enhanced MRI and routine single photon emission computed tomography (SPECT) perfusion imaging for detection of subendocardial myocardial infarcts: an imaging study. Lancet 361:374–379. https://doi.org/10.1016/S0140-6736(03)12389-6CrossRefPubMed

15.

Holly TA, Abbott BG, Al-Mallah M et al (2010) Single photon-emission computed tomography. J Nucl Cardiol 17:941–973. https://doi.org/10.1007/s12350-010-9246-yCrossRefPubMed

16.

Chugani HT, Phelps ME, Mazziotta JC (1987) Positron emission tomography study of human brain functional development. Ann Neurol 22:487–497. https://doi.org/10.1002/ana.410220408CrossRefPubMed

17.

Cohade C, Wahl RL (2003) Applications of positron emission tomography/computed tomography image fusion in clinical positron emission tomography—clinical use, interpretation methods, diagnostic improvements. Semin Nucl Med 33:228–237. https://doi.org/10.1053/snuc.2003.127312CrossRefPubMed

18.

Rudkouskaya A, Sinsuebphon N, Ward J, Tubbesing K, Intes X, Barroso M (2018) Quantitative imaging of receptor-ligand engagement in intact live animals. J Control Release Off J Control Release Soc 286:451–459. https://doi.org/10.1016/j.jconrel.2018.07.032CrossRef

19.

Ali MM, Liu G, Shah T, Flask CA, Pagel MD (2009) Using two chemical exchange saturation transfer magnetic resonance imaging contrast agents for molecular imaging studies. Acc Chem Res 42:915–924. https://doi.org/10.1021/ar8002738CrossRefPubMedPubMedCentral

20.

Liu G, Banerjee SR, Yang X, Yadav N, Lisok A, Jablonska A, Xu J, Li Y, Pomper MG, van Zijl P (2017) A dextran-based probe for the targeted magnetic resonance imaging of tumours expressing prostate-specific membrane antigen. Nat Biomed Eng 1:977–982. https://doi.org/10.1038/s41551-017-0168-8CrossRefPubMedPubMedCentral

21.

Knight JC, Mosley MJ, Kersemans V, Dias GM, Allen PD, Smart S, Cornelissen B (2019) Dual-isotope imaging allows in vivo immunohistochemistry using radiolabelled antibodies in tumours. Nucl Med Biol 70:14–22. https://doi.org/10.1016/j.nucmedbio.2019.01.010CrossRefPubMedPubMedCentral

22.

Gibbs-Strauss SL, Samkoe KS, O’Hara JA et al (2010) Detecting epidermal growth factor receptor tumor activity in vivo during cetuximab therapy of murine gliomas. Acad Radiol 17:7–17. https://doi.org/10.1016/j.acra.2009.07.027CrossRefPubMed

23.

Samkoe KS, Gibbs-Strauss SL, Yang HH, Khan Hekmatyar S, Jack Hoopes P, O’Hara JA, Kauppinen RA, Pogue BW (2011) Protoporphyrin IX fluorescence contrast in invasive glioblastomas is linearly correlated with Gd enhanced magnetic resonance image contrast but has higher diagnostic accuracy. J Biomed Opt 16:096008. https://doi.org/10.1117/1.3622754CrossRefPubMedPubMedCentral

24.

Elliott JT, Marra K, Evans LT, Davis SC, Samkoe KS, Feldwisch J, Paulsen KD, Roberts DW, Pogue BW (2017) Simultaneous in vivo fluorescent markers for perfusion, protoporphyrin metabolism, and EGFR expression for optically guided identification of orthotopic glioma. Clin Cancer Res Off J Am Assoc Cancer Res 23:2203–2212. https://doi.org/10.1158/1078-0432.CCR-16-1400CrossRef

25.

Davis SC, Dehghani H, Wang J, Jiang S, Pogue BW, Paulsen KD (2007) Image-guided diffuse optical fluorescence tomography implemented with Laplacian-type regularization. Opt Express 15:4066–4082. https://doi.org/10.1364/OE.15.004066CrossRefPubMed

26.

Davis SC, Samkoe KS, O’Hara JA, Gibbs-Strauss SL, Paulsen KD, Pogue BW (2010) Comparing implementations of magnetic-resonance-guided fluorescence molecular tomography for diagnostic classification of brain tumors. J Biomed Opt 15:051602. https://doi.org/10.1117/1.3483902CrossRefPubMedPubMedCentral

27.

Davis SC, Pogue BW, Springett R, Leussler C, Mazurkewitz P, Tuttle SB, Gibbs-Strauss SL, Jiang SS, Dehghani H, Paulsen KD (2008) Magnetic resonance–coupled fluorescence tomography scanner for molecular imaging of tissue. Rev Sci Instrum 79:064302. https://doi.org/10.1063/1.2919131CrossRefPubMedPubMedCentral

28.

Davis SC, Samkoe KS, O’Hara JA et al (2010) MRI-coupled fluorescence tomography quantifies EGFR activity in brain tumors. Acad Radiol 17:271–276. https://doi.org/10.1016/j.acra.2009.11.001CrossRefPubMedPubMedCentral

29.

Holt RW, Demers J-LH, Sexton KJ, Gunn JR, Davis SC, Samkoe KS, Pogue BW (2015) Tomography of epidermal growth factor receptor binding to fluorescent Affibody in vivo studied with magnetic resonance guided fluorescence recovery in varying orthotopic glioma sizes. J Biomed Opt 20:20. https://doi.org/10.1117/1.JBO.20.2.026001CrossRef

30.

Innis RB, Cunningham VJ, Delforge J, Fujita M, Gjedde A, Gunn RN, Holden J, Houle S, Huang SC, Ichise M, Iida H, Ito H, Kimura Y, Koeppe RA, Knudsen GM, Knuuti J, Lammertsma AA, Laruelle M, Logan J, Maguire RP, Mintun MA, Morris ED, Parsey R, Price JC, Slifstein M, Sossi V, Suhara T, Votaw JR, Wong DF, Carson RE (2007) Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab 27:1533–1539. https://doi.org/10.1038/sj.jcbfm.9600493CrossRefPubMed

31.

Bland JM, Altman DG (1995) Statistics notes: calculating correlation coefficients with repeated observations: Part 1--correlation within subjects. BMJ 310:446–446. https://doi.org/10.1136/bmj.310.6977.446CrossRefPubMedPubMedCentral

32.

Bland JM, Altman DG (1995) Calculating correlation coefficients with repeated observations: Part 2--Correlation between subjects. BMJ 310:633CrossRef

33.

Bakdash JZ, Marusich LR (2017) Repeated measures correlation. Front Psychol 8:456. https://doi.org/10.3389/fpsyg.2017.00456CrossRefPubMedPubMedCentral

34.

Lockhart AC, Liu Y, Dehdashti F, Laforest R, Picus J, Frye J, Trull L, Belanger S, Desai M, Mahmood S, Mendell J, Welch MJ, Siegel BA (2016) Phase 1 evaluation of [64Cu]DOTA-patritumab to assess dosimetry, apparent receptor occupancy, and safety in subjects with advanced solid tumors. Mol Imaging Biol 18:446–453. https://doi.org/10.1007/s11307-015-0912-yCrossRefPubMedPubMedCentral

35.

Menke-van der Houven van Oordt CW, McGeoch A, Bergstrom M et al (2019) Immuno-PET imaging to assess target engagement: experience from ⁸⁹ Zr-anti-HER3 mAb (GSK2849330) in patients with solid tumors. J Nucl Med 60:902–909. https://doi.org/10.2967/jnumed.118.214726CrossRefPubMedPubMedCentral

36.

Hijnen NM, de Vries A, Nicolay K, Grüll H (2012) Dual-isotope 111In/177Lu SPECT imaging as a tool in molecular imaging tracer design. Contrast Media Mol Imaging 7:214–222. https://doi.org/10.1002/cmmi.485CrossRefPubMed

37.

Hsieh PC, Lee IH, Yeh TL, Chen KC, Huang HC, Chen PS, Yang YK, Yao WJ, Lu RB, Chiu NT (2010) Distribution volume ratio of serotonin and dopamine transporters in euthymic patients with a history of major depression — a dual-isotope SPECT study. Psychiatry Res Neuroimaging 184:157–161. https://doi.org/10.1016/j.pscychresns.2010.09.004CrossRef

38.

Ceccarelli C, Bianchi F, Trippi D, Brozzi F, di Martino F, Santini P, Elisei R, Pinchera A (2004) Location of functioning metastases from differentiated thyroid carcinoma by simultaneous double isotope acquisition of I-131 whole body scan and bone scan. J Endocrinol Investig 27:866–869. https://doi.org/10.1007/BF03346282CrossRef

Title: Examining the Feasibility of Quantifying Receptor Availability Using Cross-Modality Paired-Agent Imaging
Authors: Boyu Meng
Negar Sadeghipour
Margaret R. Folaron
Rendall R. Strawbridge
Kimberley S. Samkoe
Kenneth M. Tichauer
Scott C. Davis
Publication date: 01-02-2022
Publisher: Springer International Publishing
Keyword: Molecular Imaging
Published in: Molecular Imaging and Biology / Issue 1/2022
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-021-01629-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Examining the Feasibility of Quantifying Receptor Availability Using Cross-Modality Paired-Agent Imaging

Abstract

Purpose

Procedures

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusion

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