Dynamic contrast enhanced MRI with clinical hepatospecific MRI contrast agents in pigs: initial experience

Hix, Jeremy M.L.; Mallett, Christiane L.; Latourette, Matthew T.; Muñoz, Kirk A.; Shapiro, Erik M.

doi:10.1101/2020.02.18.946541

Cited by 3 publications

(3 citation statements)

References 26 publications

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“…As it relates to the use of OATPs as MRI reporter proteins, OATPs with reported e cient transport of Gd-EOB-DTPA include human/primate OATP1B1 and OATP1B3 14 , rat OATP1A1 8, 11 , and rat OATP1B2 17 . Many other species, including mouse 18-20 , rabbit 21 , dog [22][23][24] and pig 25 , exhibit hepatic accumulation of Gd-EOB-DTPA and Gd-BOPTA, as evidenced by liver MRI, so it is likely that there are other members of the hepatic OATP1B family (dog OATP1B4, e.g.) that transport these agents as well.…”

Section: Introductionmentioning

confidence: 99%

MRI-Based Cell Tracking of OATP-Expressing Cell Transplants by Pre-Labeling with Gd-EOB-DTPA

Bhattacharyya,

Mallett,

Shapiro

2024

Mol Imaging Biol

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A critical step in cell-based therapies is determining the exact position of transplanted cells immediately post-transplant. Here, we devised a method to detect cell transplants immediately post-transplant, using a clinical gadolinium-based contrast agent. These cells were detected as hyperintense signals using a clinically familiar T1-weighted MRI protocol. Procedures:HEK293 cells were stably transduced to express human OATP1B3, a hepatic organic anion transporting polypeptide that transports Gd-EOB-DTPA into cells that express the transporters, the intracellular accumulation of which cells causes signal enhancement on T1-weighted MRI. Cells were pre-labeled prior to injection in media containing Gd-EOB-DTPA for MRI evaluation and indocyanine green for cryo uorescence tomography validation. Labeled cells were injected into chicken hearts, in vitro, after which MRI and cryo uorescence tomography were performed in sequence. ResultsOATP1B3-expressing cells had substantially reduced T1 following labeling with Gd-EOB-DTPA in culture.Following their implantation into chicken heart, these cells were robustly identi ed in T1-weighted MRI, with image-derived injection volumes of cells commensurate with intended injection volumes. Cryo uorescence tomography showed that the areas of signal enhancement in MRI overlapped with areas of indocyanine green signal, indicating that MRI signal enhancement was due to the transplanted cells. ConclusionsOATP1B3-expressing cells can be pre-labeled with Gd-EOB-DTPA prior to injection into tissue, affording the use of clinically familiar T1-weighted MRI to robustly detect cell transplants immediately after transplant. This procedure is easily generalizable and has potential advantages over the use of iron oxide based cell labeling agents and imaging procedures.

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Section: Introductionmentioning

confidence: 99%

MRI-Based Cell Tracking of OATP-Expressing Cell Transplants by Pre-Labeling with Gd-EOB-DTPA

Bhattacharyya,

Mallett,

Shapiro

2024

Mol Imaging Biol

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show abstract

“…As it relates to the use of OATPs as MRI reporter proteins, OATPs with reported efficient transport of Gd-EOB-DTPA include human/primate OATP1B1 and OATP1B3 14 , rat OATP1A1 8 , 11 , and rat OATP1B2 17 . Many other species, including mouse 18 – 20 , rabbit 21 , dog 22 – 24 and pig 25 , exhibit hepatic accumulation of Gd-EOB-DTPA and Gd-BOPTA, as evidenced by liver MRI, so it is likely that there are other members of the hepatic OATP1B family (dog OATP1B4, e.g.) that transport these agents as well.…”

Section: Introductionmentioning

confidence: 99%

MRI-based cell tracking of OATP-expressing cell transplants by pre-labeling with Gd-EOB-DTPA

Bhattacharyya,

Mallett,

Shapiro

2023

Preprint

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Purpose A critical step in cell-based therapies is determining the exact position of transplanted cells immediately post-transplant. Here, we devised a method to detect cell transplants immediately post-transplant, using a clinical gadolinium-based contrast agent. These cells were detected as hyperintense signals using a clinically familiar T1-weighted MRI protocol. Procedures: HEK293 cells were stably transduced to express human OATP1B3, a hepatic organic anion transporting polypeptide that transports Gd-EOB-DTPA into cells that express the transporters, the intracellular accumulation of which cells causes signal enhancement on T1-weighted MRI. Cells were pre-labeled prior to injection in media containing Gd-EOB-DTPA for MRI evaluation and indocyanine green for cryofluorescence tomography validation. Labeled cells were injected into chicken hearts, in vitro, after which MRI and cryofluorescence tomography were performed in sequence. Results OATP1B3-expressing cells had substantially reduced T1 following labeling with Gd-EOB-DTPA in culture. Following their implantation into chicken heart, these cells were robustly identified in T1-weighted MRI, with image-derived injection volumes of cells commensurate with intended injection volumes. Cryofluorescence tomography showed that the areas of signal enhancement in MRI overlapped with areas of indocyanine green signal, indicating that MRI signal enhancement was due to the transplanted cells. Conclusions OATP1B3-expressing cells can be pre-labeled with Gd-EOB-DTPA prior to injection into tissue, affording the use of clinically familiar T1-weighted MRI to robustly detect cell transplants immediately after transplant. This procedure is easily generalizable and has potential advantages over the use of iron oxide based cell labeling agents and imaging procedures.

show abstract

“…As it relates to the use of OATPs as MRI reporter proteins, OATPs with reported efficient transport of Gd-EOB-DTPA include human/primate OATP1B1 and OATP1B3 14 , rat OATP1A1 8,11 , and rat OATP1B2 17 . Many other species, including mouse [18][19][20] , rabbit 21 , dog [22][23][24] and pig 25 , exhibit hepatic accumulation of Gd-EOB-DTPA and Gd-BOPTA, as evidenced by liver MRI, so it is likely that there are other members of the hepatic OATP1B family (dog OATP1B4, e.g.) that transport these agents as well.…”

mentioning

confidence: 99%

MRI-based cell tracking of OATP-expressing cell transplants by pre-labeling with Gd-EOB-DTPA

Bhattacharyya

Mallett

Shapiro

2023

Preprint

Self Cite

View full text Add to dashboard Cite

MRI-based cell tracking can play a key role in clinical cell therapies and is most useful when the high-resolution and spatial discrimination capabilities of MRI are used for determining the precise locations of transplanted cells. Traditionally, iron oxide nanoparticles are used for magnetic cell labeling with detection of labeled cells via T2/T2*-weighted MRI, however, the dark contrast obscures the underlying anatomy, and making quantification of cell number difficult. Bright contrast methods have been sparingly used for MRI-based cell tracking employing Gd-chelates and Mn2+, accumulated intracellularly by disruptive (photoporation, transfection, etc) methods or by simple incubation, respectively. Further, 19F agents have been used for MRI-based cell tracking. Yet, MRI-based cell tracking has not made significant clinical impact, partly due to the complications of cell labeling and detection. Hepatic organic anion transporting polypeptides (OATPs) transport off-the-shelf, FDA-approved, hepatospecific Gd-based MRI contrast agents into cells that express the transporters, the intracellular accumulation of which cells causes signal enhancement on clinically familiar T1-weighted MRI. We show that OATP-expressing cells can be pre-labeled with Gd-EOB-DTPA prior to injection affording the use of clinically familiar T1-weighted MRI to robustly detect cell transplants. This straightforward approach to labeling and MRI detection may facilitate the incorporation of MRI-based cell tracking in clinical trials and cell therapies.

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Dynamic contrast enhanced MRI with clinical hepatospecific MRI contrast agents in pigs: initial experience

Cited by 3 publications

References 26 publications

MRI-Based Cell Tracking of OATP-Expressing Cell Transplants by Pre-Labeling with Gd-EOB-DTPA

MRI-Based Cell Tracking of OATP-Expressing Cell Transplants by Pre-Labeling with Gd-EOB-DTPA

MRI-based cell tracking of OATP-expressing cell transplants by pre-labeling with Gd-EOB-DTPA

MRI-based cell tracking of OATP-expressing cell transplants by pre-labeling with Gd-EOB-DTPA

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