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Article ; Online: Liver and spleen predominantly mediate calciprotein particle clearance in a rat model of chronic kidney disease.

Zeper, Lara W / Bos, Caro / Leermakers, Pieter A / Franssen, Gerben M / Raavé, René / Hoenderop, Joost G J / de Baaij, Jeroen H F

American journal of physiology. Renal physiology

2024 Volume 326, Issue 4, Page(s) F622–F634

Abstract: Calciprotein particles (CPPs) provide an efficient mineral buffering system to prevent the complexation of phosphate and calcium in the circulation. However, in chronic kidney disease (CKD), the phosphate load exceeds the mineral buffering capacity, ... ...

Abstract	Calciprotein particles (CPPs) provide an efficient mineral buffering system to prevent the complexation of phosphate and calcium in the circulation. However, in chronic kidney disease (CKD), the phosphate load exceeds the mineral buffering capacity, resulting in the formation of crystalline CPP2 particles. CPP2 have been associated with cardiovascular events and mortality. Moreover, CPP2 have been demonstrated to induce calcification in vitro. In this study, we examined the fate of CPP2 in a rat model of CKD. Calcification was induced in Sprague-Dawley rats by 5/6 nephrectomy (5/6-Nx) combined with a high-phosphate diet. Control rats received sham surgery and high-phosphate diet. Twelve weeks after surgery, kidney failure was significantly induced in 5/6-Nx rats as determined by enhanced creatinine and urea plasma levels and abnormal kidney histological architecture. Subsequently, radioactive and fluorescent (FITC)-labeled CPP2 ([
MeSH term(s)	Rats ; Animals ; Spleen/metabolism ; Calcium/metabolism ; Fluorescein-5-isothiocyanate ; Tissue Distribution ; Rats, Sprague-Dawley ; Vascular Calcification/diagnostic imaging ; Vascular Calcification/etiology ; Minerals ; Liver/metabolism ; Phosphates ; Renal Insufficiency, Chronic/pathology
Chemical Substances	Calcium (SY7Q814VUP) ; Fluorescein-5-isothiocyanate (I223NX31W9) ; Minerals ; Phosphates
Language	English
Publishing date	2024-02-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00239.2023
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Article ; Online: New Long-Acting [

Wilbs, Jonas / Raavé, René / Boswinkel, Milou / Glendorf, Tine / Rodríguez, David / Fernandes, Eduardo Felipe Alves / Heskamp, Sandra / Bjørnsdottir, Inga / Gustafsson, Magnus B F

Journal of medicinal chemistry

2023 Volume 66, Issue 12, Page(s) 7772–7784

Abstract: Positron emission tomography (PET) imaging is used in drug development to noninvasively measure biodistribution and receptor occupancy. Ideally, PET tracers retain target binding and biodistribution properties of the investigated drug. Previously, we ... ...

Abstract	Positron emission tomography (PET) imaging is used in drug development to noninvasively measure biodistribution and receptor occupancy. Ideally, PET tracers retain target binding and biodistribution properties of the investigated drug. Previously, we developed a zirconium-89 PET tracer based on a long-circulating glucagon-like peptide 1 receptor agonist (GLP-1RA) using desferrioxamine (DFO) as a chelator. Here, we aimed to develop an improved zirconium-89-labeled GLP-1RA with increased molar activity to increase the uptake in low receptor density tissues, such as brain. Furthermore, we aimed at reducing tracer accumulation in the kidneys. Introducing up to four additional Zr-DFOs resulted in higher molar activity and stability, while retaining potency. Branched placement of DFOs was especially beneficial. Tracers with either two or four DFOs had similar biodistribution as the tracer with one DFO in vivo, albeit increased kidney and liver uptake. Reduced kidney accumulation was achieved by introducing an enzymatically cleavable Met-Val-Lys (MVK) linker motif between the chelator and the peptide.
MeSH term(s)	Deferoxamine/chemistry ; Tissue Distribution ; Positron-Emission Tomography/methods ; Zirconium/chemistry ; Chelating Agents/chemistry ; Kidney/diagnostic imaging ; Cell Line, Tumor
Chemical Substances	Zirconium-89 (NTM296JU95) ; Deferoxamine (J06Y7MXW4D) ; Zirconium (C6V6S92N3C) ; Chelating Agents
Language	English
Publishing date	2023-03-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.2c02073
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Article ; Online: Chemotherapeutic drug delivery by tumoral extracellular matrix targeting.

Raavé, René / van Kuppevelt, Toin H / Daamen, Willeke F

Journal of controlled release : official journal of the Controlled Release Society

2018 Volume 274, Page(s) 1–8

Abstract: Systemic chemotherapy is a primary strategy in the treatment of cancer, but comes with a number of limitations such as toxicity and unfavorable biodistribution. To overcome these issues, numerous targeting systems for specific delivery of ... ...

Abstract	Systemic chemotherapy is a primary strategy in the treatment of cancer, but comes with a number of limitations such as toxicity and unfavorable biodistribution. To overcome these issues, numerous targeting systems for specific delivery of chemotherapeutics to tumor cells have been designed and evaluated. Such strategies generally address subsets of tumor cells, still allowing the progressive growth of tumor cells not expressing the target. Moreover, tumor stem cells and tumor supportive cells, such as cancer associated fibroblasts and cancer associated macrophages, are left unaffected by this approach. In this review, we discuss an alternative targeting strategy aimed at delivery of anti-tumor drugs to the tumoral extracellular matrix with the potential to eliminate all cell types. The extracellular matrix of tumors is vastly different from that of healthy tissue and offers hooks for targeted drug delivery. It is concluded that matrix targeting is promising, but that clinical studies are required to evaluate translation.
MeSH term(s)	Animals ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Drug Carriers ; Drug Delivery Systems ; Drug Liberation ; Humans ; Molecular Targeted Therapy ; Tumor Microenvironment/drug effects
Chemical Substances	Antineoplastic Agents ; Drug Carriers
Language	English
Publishing date	2018-01-31
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2018.01.029
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Article: Chemotherapeutic drug delivery by tumoral extracellular matrix targeting

Raavé, René / Toin H. van Kuppevelt / Willeke F. Daamen

Journal of controlled release. 2018 Mar. 28, v. 274

2018

Abstract	Systemic chemotherapy is a primary strategy in the treatment of cancer, but comes with a number of limitations such as toxicity and unfavorable biodistribution. To overcome these issues, numerous targeting systems for specific delivery of chemotherapeutics to tumor cells have been designed and evaluated. Such strategies generally address subsets of tumor cells, still allowing the progressive growth of tumor cells not expressing the target. Moreover, tumor stem cells and tumor supportive cells, such as cancer associated fibroblasts and cancer associated macrophages, are left unaffected by this approach. In this review, we discuss an alternative targeting strategy aimed at delivery of anti-tumor drugs to the tumoral extracellular matrix with the potential to eliminate all cell types. The extracellular matrix of tumors is vastly different from that of healthy tissue and offers hooks for targeted drug delivery. It is concluded that matrix targeting is promising, but that clinical studies are required to evaluate translation.
Keywords	antineoplastic agents ; clinical trials ; drug therapy ; extracellular matrix ; fibroblasts ; macrophages ; neoplasm cells ; neoplasms ; stem cells ; toxicity
Language	English
Dates of publication	2018-0328
Size	p. 1-8.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2018.01.029
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Comparison of the Tissue Distribution of a Long-Circulating Glucagon-like Peptide-1 Agonist Determined by Positron Emission Tomography and Quantitative Whole-Body Autoradiography.

Fernandes, Eduardo Felipe Alves / Wilbs, Jonas / Raavé, Rene / Jacobsen, Christian Borch / Toftelund, Hanne / Helleberg, Hans / Boswinkel, Milou / Heskamp, Sandra / Gustafsson, Magnus Bernt Frederik / Bjørnsdottir, Inga

ACS pharmacology & translational science

2022 Volume 5, Issue 8, Page(s) 616–624

Abstract: Positron emission tomography (PET) is a molecular imaging modality that enables non-invasive visualization of tracer distribution and pharmacology. Recently, peptides with long half-lives allowed once-a-week dosing of glucagon-like peptide-1 receptor ( ... ...

Abstract	Positron emission tomography (PET) is a molecular imaging modality that enables non-invasive visualization of tracer distribution and pharmacology. Recently, peptides with long half-lives allowed once-a-week dosing of glucagon-like peptide-1 receptor (GLP-1R) agonists with therapeutic applications in diabetes and obesity. PET imaging for such long-lived peptides is hindered by the typically used short-lived radionuclides. Zirconium-89 (
Language	English
Publishing date	2022-06-30
Publishing country	United States
Document type	Journal Article
ISSN	2575-9108
ISSN (online)	2575-9108
DOI	10.1021/acsptsci.2c00075
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Article ; Online: Site-Specific, Platform-Based Conjugation Strategy for the Synthesis of Dual-Labeled Immunoconjugates for Bimodal PET/NIRF Imaging of HER2-Positive Tumors.

Adumeau, Pierre / Raavé, René / Boswinkel, Milou / Heskamp, Sandra / Wessels, Hans J C T / van Gool, Alain J / Moreau, Mathieu / Bernhard, Claire / Da Costa, Laurène / Goncalves, Victor / Denat, Franck

Bioconjugate chemistry

2022 Volume 33, Issue 3, Page(s) 530–540

Abstract: Because positron emission tomography (PET) and optical imaging are very complementary, the combination of these two imaging modalities is very enticing in the oncology field. Such bimodal imaging generally relies on imaging agents bearing two different ... ...

Abstract	Because positron emission tomography (PET) and optical imaging are very complementary, the combination of these two imaging modalities is very enticing in the oncology field. Such bimodal imaging generally relies on imaging agents bearing two different imaging reporters. In the bioconjugation field, this is mainly performed by successive random conjugations of the two reporters on the protein vector, but these random conjugations can alter the vector properties. In this study, we aimed at abrogating the heterogeneity of the bimodal imaging immunoconjugate and mitigating the impact of multiple random conjugations. A trivalent platform bearing a DFO chelator for
MeSH term(s)	Cell Line, Tumor ; Fluorescent Dyes/chemistry ; Humans ; Immunoconjugates/chemistry ; Neoplasms ; Positron-Emission Tomography/methods ; Radioisotopes/chemistry ; Tissue Distribution ; Zirconium/chemistry
Chemical Substances	Fluorescent Dyes ; Immunoconjugates ; Radioisotopes ; Zirconium (C6V6S92N3C)
Language	English
Publishing date	2022-03-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1024041-x
ISSN	1520-4812 ; 1043-1802
ISSN (online)	1520-4812
ISSN	1043-1802
DOI	10.1021/acs.bioconjchem.2c00049
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Article: Elucidating the Influence of Tumor Presence on the Polymersome Circulation Time in Mice.

de Kruijff, Robin M / Raavé, René / Kip, Annemarie / Molkenboer-Kuenen, Janneke / Roobol, Stefan J / Essers, Jeroen / Heskamp, Sandra / Denkova, Antonia G

Pharmaceutics

2019 Volume 11, Issue 5

Abstract: The use of nanoparticles as tumor-targeting agents is steadily increasing, and the influence of nanoparticle characteristics such as size and stealthiness have been established for a large number of nanocarrier systems. However, not much is known about ... ...

Abstract	The use of nanoparticles as tumor-targeting agents is steadily increasing, and the influence of nanoparticle characteristics such as size and stealthiness have been established for a large number of nanocarrier systems. However, not much is known about the impact of tumor presence on nanocarrier circulation times. This paper reports on the influence of tumor presence on the in vivo circulation time and biodistribution of polybutadiene-polyethylene oxide (PBd-PEO) polymersomes. For this purpose, polymersomes were loaded with the gamma-emitter
Keywords	covid19
Language	English
Publishing date	2019-05-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics11050241
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Article ; Online: Direct In Vivo Activation of T Cells with Nanosized Immunofilaments Inhibits Tumor Growth and Metastasis.

ACS nano

2023 Volume 17, Issue 13, Page(s) 12101–12117

Abstract: Adoptive T cell therapy has successfully been implemented for the treatment of cancer. Nevertheless, ex vivo expansion of T cells by artificial antigen-presenting cells (aAPCs) remains cumbersome and can compromise T cell functionality, thereby limiting ... ...

Abstract	Adoptive T cell therapy has successfully been implemented for the treatment of cancer. Nevertheless, ex vivo expansion of T cells by artificial antigen-presenting cells (aAPCs) remains cumbersome and can compromise T cell functionality, thereby limiting their therapeutic potential. We propose a radically different approach aimed at direct expansion of T cells in vivo, thereby omitting the need for large-scale ex vivo T cell production. We engineered nanosized immunofilaments (IFs), with a soluble semiflexible polyisocyanopeptide backbone that presents peptide-loaded major histocompatibility complexes and costimulatory molecules multivalently. IFs readily activated and expanded antigen-specific T cells like natural APCs, as evidenced by transcriptomic analyses of T cells. Upon intravenous injection, IFs reach the spleen and lymph nodes and induce antigen-specific T cell responses in vivo. Moreover, IFs display strong antitumor efficacy resulting in inhibition of the formation of melanoma metastases and reduction of primary tumor growth in synergy with immune checkpoint blockade. In conclusion, nanosized IFs represent a powerful modular platform for direct activation and expansion of antigen-specific T cells in vivo, which can greatly contribute to cancer immunotherapy.
MeSH term(s)	Humans ; T-Lymphocytes ; Antigen-Presenting Cells ; Melanoma/therapy ; Immunotherapy ; Immunotherapy, Adoptive
Language	English
Publishing date	2023-06-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1936-086X
ISSN (online)	1936-086X
DOI	10.1021/acsnano.2c11884
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Article ; Online: 89

Heskamp, Sandra / Raavé, René / Boerman, Otto / Rijpkema, Mark / Goncalves, Victor / Denat, Franck

Bioconjugate chemistry

2017 Volume 28, Issue 9, Page(s) 2211–2223

Abstract: Immuno-positron emission tomography (immunoPET) ... ...

Abstract	Immuno-positron emission tomography (immunoPET) with
MeSH term(s)	Animals ; Chelating Agents/chemistry ; Chelating Agents/pharmacokinetics ; Deferoxamine/chemistry ; Deferoxamine/pharmacokinetics ; Drug Delivery Systems/methods ; Drug Discovery/methods ; Humans ; Immunoconjugates/chemistry ; Immunoconjugates/pharmacokinetics ; Neoplasms/diagnosis ; Neoplasms/drug therapy ; Neoplasms/therapy ; Positron-Emission Tomography/methods ; Radiochemistry/methods ; Radioisotopes/chemistry ; Radioisotopes/pharmacokinetics ; Zirconium/chemistry ; Zirconium/pharmacokinetics
Chemical Substances	Chelating Agents ; Immunoconjugates ; Radioisotopes ; Zirconium (C6V6S92N3C) ; Deferoxamine (J06Y7MXW4D)
Language	English
Publishing date	2017-09-20
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1024041-x
ISSN	1520-4812 ; 1043-1802
ISSN (online)	1520-4812
ISSN	1043-1802
DOI	10.1021/acs.bioconjchem.7b00325
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Article ; Online: Tracers for non-invasive radionuclide imaging of immune checkpoint expression in cancer.

Wierstra, Peter / Sandker, Gerwin / Aarntzen, Erik / Gotthardt, Martin / Adema, Gosse / Bussink, Johan / Raavé, René / Heskamp, Sandra

EJNMMI radiopharmacy and chemistry

2019 Volume 4, Issue 1, Page(s) 29

Abstract: Immunotherapy with checkpoint inhibitors demonstrates impressive improvements in the treatment of several types of cancer. Unfortunately, not all patients respond to therapy while severe immune-related adverse effects are prevalent. Currently, patient ... ...

Abstract	Immunotherapy with checkpoint inhibitors demonstrates impressive improvements in the treatment of several types of cancer. Unfortunately, not all patients respond to therapy while severe immune-related adverse effects are prevalent. Currently, patient stratification is based on immunotherapy marker expression through immunohistochemical analysis on biopsied material. However, expression can be heterogeneous within and between tumor lesions, amplifying the sampling limitations of biopsies. Analysis of immunotherapy target expression by non-invasive quantitative molecular imaging with PET or SPECT may overcome this issue. In this review, an overview of tracers that have been developed for preclinical and clinical imaging of key immunotherapy targets, such as programmed cell death-1, programmed cell death ligand-1, IDO1 and cytotoxic T lymphocyte-associated antigen-4 is presented. We discuss important aspects to consider when developing such tracers and outline the future perspectives of molecular imaging of immunotherapy markers. Current techniques in immune checkpoint imaging and its potential for future applications.
Language	English
Publishing date	2019-11-06
Publishing country	England
Document type	Journal Article ; Review
ISSN	2365-421X
ISSN (online)	2365-421X
DOI	10.1186/s41181-019-0078-z
Database	MEDical Literature Analysis and Retrieval System OnLINE

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