Islet Transplantation Imaging in vivo

Figures & data

Figure 1 Islets transplantation imaging of MRI, SPECT and PET. (A) In vivo MR imaging of recipients having transplanted islets. In vivo spin echo T2-weighted axial MR images of heparin-SPIO-conjugated islets 30 days after xenotransplantation under the renal subcapsular membrane of left kidney in nude mice (300 islet equivalent/mouse). The dark area in the left kidney represents a labeled islet graft. Arrow: transplantation site. Reprinted from Biomaterials. 32(35). Jung MJ, Lee SS, Hwang YH, et al.MRI of transplanted surface-labeled pancreatic islets with heparinized superparamagnetic iron oxide nanoparticles. 9391–9400, Copyright (2011), with permission from Elsevier.²¹ (B) Transplanted islets under the left kidney capsule of CD1 mice labeled by 111In-tropolone was imaged by three-dimensional reconstructions SPECT/CT. This research was originally published in J Nucl Med. Tai JH, Nguyen B, Wells RG, et al. Imaging of gene expression in live pancreatic islet cell lines using dual-isotope SPECT. J Nucl Med. 2007;49(1):94–102. ©SNMMI. http://jnm.snmjournals.org/content/49/1/94.short.³⁹ (C) PET images were obtained after the [⁶⁸Ga]DO3A-VS-Cys40-Exendin-4 intravenous injections via the tail in NOD/SCID mice with human-transplanted islets in the liver. The liver with transplanted islets demonstrate prominent tracer uptake (arrow). Reproduced from Junfeng L, Rawson J, et al. Evaluation of [68Ga]DO3A-VSCys40- exendin-4 as a PET probe for imaging human transplanted islets in the liver. Sci Rep. 2019;9:5705. Creative Commons license and disclaimer available from: http://creativecommons.org/licenses/by/4.0/legalcode.⁵⁶

Figure 2 Islets transplantation imaging of FI, BLI and US. (A) Transplanted rat islets were detected by PiF fluorescence imaging. Reprinted with permission from Kang NY, Lee JY, Lee SH, et al. Multimodal imaging probe development for pancreatic β cells: from fluorescence to PET. J Am Chem Soc. 2020;142(7):3430–3439. Copyright (2020) American Chemical Society.⁷⁹ (B) 500 human islets were transduced with Adeno-CMV-Luc and implanted under the left kidney capsule of NOD-SCID mice. A representative CCD image 3 days postimplantation is shown. Reprinted from Mol Ther. 9(3). Lu Y, Dang H, Middleton B, et al. Bioluminescent monitoring of islet graft survival after transplantation.  428–435, Copyright 2004, with permission from Elsevier.⁶⁵ (C) Intraoperative ultrasound findings of the portal vein. The transplanted islets appeared as hyperechoic clusters in the portal vein (arrows). Reproduced from Sakata N, Goto M, Gumpei Y, et al. Intraoperative ultrasound examination is useful for monitoring transplanted islets: a case report. Islets. 2012;4(5):339–342, reprinted by permission of the publisher (Taylor & Francis Ltd, hhtp://www.tandfonline.com).⁷⁰

Figure 3 Trimodal imaging of transplanted pancreatic islets in scaffolds. Representative (A) bioluminescence, (B) fluorescence, and (C) axial F-19/H-1 MR images of 3000 and 1000 pancreatic islets transplanted into scaffolds on days 4. Reproduced from Gálisová A, Herynek V, Swider E, et al. A trimodal imaging platform for tracking viable transplanted pancreatic islets in vivo: F-19 MR, fluorescence, and bioluminescence imaging. Mol Imaging Biol. 2019;21(3):454Y464. Creative Commons license and disclaimer available from: http://creativecommons.org/licenses/by/4.0/legalcode.¹¹

Table 1 Advantages and Disadvantages of Imaging Modalities of Islets

	Advantages	Disadvantages	Contrast Agent
MRI	High spatial resolution, Deep tissue penetration, Tomographic capability, No radiation, Repeatability	Low sensitivity, Toxicity of contrast agent, Difficulty of distinguishing between live and dead islets, Pre-labeling islets before transplantation	SPIO, Gd, Mn^2+, Zn^2+,19F
SPECT	High resolution, Deep tissue penetration, High sensitivity, Functional evaluation of islets	Low spatial and anatomical resolution, Ionizing radiation	^99mTc, ^111In, ^123I, ^131I
PET	High resolution, Deep tissue penetration, Higher sensitivity, Functional evaluation of islets	Low spatial and anatomical resolution, Ionizing radiation	^11C, ^18F, ^68Ga, ^64Cu
FI	High sensitivity, Quantitative evaluation of islets, No radiation	Short period of cancellation, Poor tissue penetration, Low spatial resolution	GFP, RFP, FITC, Cy-5.5
BLI	Long-term observation, High sensitivity, Quantitative evaluation of islets, No radiation	Susceptible to internal environment, Weak signal, Low spatial resolution	Luciferin
US	Simple operation, No radiation, Repeatability, No adverse effects	Operator dependency, Low sensitivity, Weak signal, cannot visualize single islets
MPI	No radiation, high temporal resolution, high spatial resolution and high sensitivity	No anatomical background.	Magnetic particle
PAI	High resolution, Deep tissue penetration, No ionizing radiation Diverse endogenous and exogenous contrast,	Reproducibility and standardization of the images
Multimodality imaging	Combining the advantages of various imaging modalities	High costs, Complexity design of Contrast agent, The long-term effects on the human body need further study	Nanoparticles

Jung MJ, Lee SS, Hwang YH, et al. MRI of transplanted surface-labeled pancreatic islets with heparinized superparamagnetic iron oxide nanoparticles. Biomaterials. 2011;32(35):9391e9400. doi:10.1016/j.biomaterials.2011.08.070

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Tai JH, Nguyen B, Wells RG, et al. Imaging of gene expression in live pancreatic islet cell lines using dual-isotope SPECT. J Nucl Med. 2007;49(1):94–102. doi:10.2967/jnumed.107.043430

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Junfeng L, Rawson J, Chea J, et al. Evaluation of [68Ga]DO3A-VSCys40- exendin-4 as a PET probe for imaging human transplanted islets in the liver. Sci Rep. 2019;9:5705. doi:10.1038/s41598-019-42172-3

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Kang N-Y, Lee JY, Lee SH, et al. Multimodal imaging probe development for pancreatic β cells: from fluorescence to PET. J Am Chem Soc. 2020;142(7):3430–3439. doi:10.1021/jacs.9b11173

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Lu Y, Dang H, Middleton B, et al. Bioluminescent monitoring of islet graft survival after transplantation. Mol Ther. 2004;9(3):428–435. doi:10.1016/j.ymthe.2004.01.008

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Sakata N, Goto M, Gumpei Y, et al. Intraoperative ultrasound examination is useful for monitoring transplanted islets: a case report. Islets. 2012;4(5):339–342. doi:10.4161/isl.22384

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Gálisová A, Herynek V, Swider E, et al. A trimodal imaging platform for tracking viable transplanted pancreatic islets in vivo: F-19 MR, fluorescence, and bioluminescence imaging. Mol Imaging Biol. 2019;21(3):454Y464. doi:10.1007/s11307-018-1270-3

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