Radio-metal cross-linking of alginate hydrogels for non-invasive in vivo imaging

Patrick, P. Stephen; Bear, Joseph C.; Fitzke, H; Thin, May Zaw; Parkin, Ivan P.; Lythgoe, Mark F.; Kalber, Tammy L.; Stuckey, Daniel J.

doi:10.1016/j.biomaterials.2020.119930

Cited by 35 publications

(38 citation statements)

References 53 publications

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“…[27] Injection of an alginate hydrogel cross-linked with radio-metal 111 In showed a cardiac retention of 2%-4%, one week postinjection. [16] As a highly vascularized organ, it is likely this accumulation of 111 In signal reflects dissolved UPy-polymers that enter the lungs via the coronary veins or the central circulation. Previously, we have shown that the UPy-polymers do not affect biocompatibility or induce toxicity.…”

Section: In Vivo Injection In Pig Heart and Scintigraphymentioning

confidence: 99%

“…[11][12][13] Only a few studies examined the degree of hydrogel retention after injection and the potential off-target distribution of the gel, mainly in small animal models. [14][15][16] A collagen matrix delivery in a mouse model with MI was assessed on its retention and distribution by Positron Emission Tomography (PET) imaging, where the hydrogel was labeled with hexadecyl-4-[( 18)F]fluorobenzoate ((18)F-HFB). [17] A more recent study showed in vivo nuclear imaging of an alginate hydrogel in which the nuclear imaging radio-metal indium-111 ( 111 In) was incorporated.…”

Section: Introductionmentioning

confidence: 99%

“…[ 17 ] A more recent study showed in vivo nuclear imaging of an alginate hydrogel in which the nuclear imaging radio‐metal indium‐111 ( 111 In) was incorporated. [ 16 ] Intramyocardial injection in mice was performed, where a low retention was observed after 1 week (2–4%). To our knowledge, no study has provided quantitative numbers on the amount of cardiac retention and distribution of a supramolecular hydrogel in a large animal model.…”

Section: Introductionmentioning

confidence: 99%

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In Vivo Retention Quantification of Supramolecular Hydrogels Engineered for Cardiac Delivery

Schotman

Peters

Krijger

et al. 2021

Adv Healthcare Materials

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Recent advances in the field of cardiac regeneration show great potential in the use of injectable hydrogels to reduce immediate flush-out of injected factors, thereby increasing the effectiveness of the encapsulated drugs. To establish a relation between cardiac function and retention of the drug-encapsulating hydrogel, a quantitative in vivo imaging method is required. Here, the supramolecular ureido-pyrimidinone modified poly(ethylene glycol) (UPy-PEG) material is developed into a bioactive hydrogel for radioactive imaging in a large animal model. A radioactive label is synthesized, being a ureido-pyrimidinone moiety functionalized with a chelator (UPy-DOTA) complexed with the radioactive isotope indium-111 (UPy-DOTA-111 In) that is mixed with the hydrogel. Additionally, bioactive and adhesive properties of the UPy-PEG hydrogel are increased by supramolecular introduction of a UPy-functionalized recombinant collagen type 1-based material (UPy-PEG-RCPhC1). This method enables in vivo tracking of the nonbioactive and bioactive supramolecular hydrogels and quantification of hydrogel retention in a porcine heart. In a small pilot, cardiac retention values of 8% for UPy-PEG and 16% for UPy-PEG-RCPhC1 hydrogel are observed 4 h postinjection. This work highlights the importance of retention quantification of hydrogels in vivo, where elucidation of hydrogel quantity at the target site is proposed to strongly influence efficacy of the intended therapy.

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Section: In Vivo Injection In Pig Heart and Scintigraphymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In Vivo Retention Quantification of Supramolecular Hydrogels Engineered for Cardiac Delivery

Schotman

Peters

Krijger

et al. 2021

Adv Healthcare Materials

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“…However, by combining ultrasound contrast agents with 1 H or 19 F MRI, nuclear, CT or photoacoustic cell imaging approaches, quantitative data on whole-body distribution and long-term cell retention can be acquired [102À105]. This multimodal approach becomes more impactful when combined with non-invasive, ultrasound-guided delivery of cells directly to the specific target organ [106,107]. Using this method, both needle position and cell injection can be assessed in real time, informing upon the success of cell delivery.…”

Section: Ultrasoundmentioning

confidence: 99%

Options for imaging cellular therapeutics in vivo: a multi-stakeholder perspective

et al. 2021

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Cell-based therapies have been making great advances toward clinical reality. Despite the increase in trial activity, few therapies have successfully navigated late-phase clinical trials and received market authorization. One possible explanation for this is that additional tools and technologies to enable their development have only recently become available. To support the safety evaluation of cell therapies, the Health and Environmental Sciences Institute Cell Therapy-Tracking, Circulation and Safety Committee, a multisector collaborative committee, polled the attendees of the 2017 International Society for Cell & Gene Therapy conference in London, UK, to understand the gaps and needs that cell therapy developers have encountered regarding safety evaluations in vivo. The goal of the survey was to collect information to inform stakeholders of areas of interest that can help ensure the safe use of cellular therapeutics in the clinic. This review is a response to the cellular imaging interests of those respondents. The authors offer a brief overview of available technologies and then highlight the areas of interest from the survey by describing how imaging technologies can meet those needs. The areas of interest include imaging of cells over time, sensitivity of imaging modalities, ability to quantify cells, imaging cellular survival and differentiation and safety concerns around adding imaging agents to cellular therapy protocols. The Health and Environmental Sciences Institute Cell Therapy-Tracking, Circulation and Safety Committee believes that the ability to understand therapeutic cell fate is vital for determining and understanding cell therapy efficacy and safety and offers this review to aid in those needs. An aim of this article is to share the available imaging technologies with the cell therapy community to demonstrate how these technologies can accomplish unmet needs throughout the translational process and strengthen the understanding of cellular therapeutics.

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“…Radiolabeling small molecules, proteins, and biomaterials typically involves the use of covalent or electrostatic binding (64) or ionic cross-linking (65). Alternatively, nonspecific metabolic radiotracers can be taken up by cells and have been used to track the fate of administered peripheral blood CD34 + cells (66) and the engraftment of islet cells (67).…”

Section: In Vivo Monitoringmentioning

confidence: 99%

A blueprint for translational regenerative medicine

et al. 2020

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The past few decades have produced a large number of proof-of-concept studies in regenerative medicine. However, the route to clinical adoption is fraught with technical and translational obstacles that frequently consign promising academic solutions to the so-called “valley of death.” Here, we present a proposed blueprint for translational regenerative medicine. We offer principles to help guide the selection of cells and materials, present key in vivo imaging modalities, and argue that the host immune response should be considered throughout design and development. Last, we suggest a pathway to navigate the often complex regulatory and manufacturing landscape of translational regenerative medicine.

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Radio-metal cross-linking of alginate hydrogels for non-invasive in vivo imaging

Cited by 35 publications

References 53 publications

In Vivo Retention Quantification of Supramolecular Hydrogels Engineered for Cardiac Delivery

In Vivo Retention Quantification of Supramolecular Hydrogels Engineered for Cardiac Delivery

Options for imaging cellular therapeutics in vivo: a multi-stakeholder perspective

A blueprint for translational regenerative medicine

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