Preclinical Evaluation of [ 11 C]YC-72-AB85 for In Vivo Visualization of Heat Shock Protein 90 in Brain and Cancer with Positron Emission Tomography

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Preclinical Evaluation of [ 11 C]YC-72-AB85 for In Vivo Visualization of Heat Shock Protein 90 in Brain and Cancer with Positron Emission Tomography. / Vermeulen, Koen; Cools, Romy ; Briard, Emmanuelle; Auberson, Yves; Schoepfer, Joseph; Koole, Michel; Cawthorne, Christopher; Bormans, Guy.

In: ACS Chemical Neuroscience, Vol. 12, No. 20, 1c00508, 20.10.2021, p. 3915-3927.

Research output: Contribution to journalArticlepeer-review

Harvard

Vermeulen, K, Cools, R, Briard, E, Auberson, Y, Schoepfer, J, Koole, M, Cawthorne, C & Bormans, G 2021, 'Preclinical Evaluation of [ 11 C]YC-72-AB85 for In Vivo Visualization of Heat Shock Protein 90 in Brain and Cancer with Positron Emission Tomography', ACS Chemical Neuroscience, vol. 12, no. 20, 1c00508, pp. 3915-3927. https://doi.org/10.1021/acschemneuro.1c00508

APA

Vermeulen, K., Cools, R., Briard, E., Auberson, Y., Schoepfer, J., Koole, M., Cawthorne, C., & Bormans, G. (2021). Preclinical Evaluation of [ 11 C]YC-72-AB85 for In Vivo Visualization of Heat Shock Protein 90 in Brain and Cancer with Positron Emission Tomography. ACS Chemical Neuroscience, 12(20), 3915-3927. [1c00508]. https://doi.org/10.1021/acschemneuro.1c00508

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Author

Vermeulen, Koen ; Cools, Romy ; Briard, Emmanuelle ; Auberson, Yves ; Schoepfer, Joseph ; Koole, Michel ; Cawthorne, Christopher ; Bormans, Guy. / Preclinical Evaluation of [ 11 C]YC-72-AB85 for In Vivo Visualization of Heat Shock Protein 90 in Brain and Cancer with Positron Emission Tomography. In: ACS Chemical Neuroscience. 2021 ; Vol. 12, No. 20. pp. 3915-3927.

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@article{7587ca9d9efc49b4a9d0b96f3070fc10,
title = "Preclinical Evaluation of [ 11 C]YC-72-AB85 for In Vivo Visualization of Heat Shock Protein 90 in Brain and Cancer with Positron Emission Tomography",
abstract = "Aberrant Hsp90 has been implied in cancer and neurodegenerative disorders. The development of a suitable Hsp90 Positron emission tomography (PET) probe can provide in vivo quantification of the expression levels of Hsp90 as a biomarker for diagnosis and follow-up of cancer and central nervous system (CNS) disease progression. In this respect, [11C]YC-72-AB85 was evaluated as an Hsp90 PET probe in B16.F10 melanoma bearing mice and its brain uptake was determined in rats and nonhuman primate. In vitro binding of [11C]YC-72-AB85 to tissue slices of mouse B16.F10 melanoma, PC3 prostate carcinoma, and rodent brain was evaluated using autoradiography. Biodistribution of [11C]YC-72-AB85 was evaluated in healthy and B16.F10 melanoma mice. In vivo brain uptake was assessed by μPET studies in rats and a rhesus monkey. In vitro binding was deemed Hsp90-specific by blocking studies with heterologous Hsp90 inhibitors onalespib and SNX-0723. Saturable Hsp90 binding was observed in brain, tumor, blood, and blood-rich organs in mice. In combined pretreatment and displacement studies, reversible and Hsp90-specific binding of [11C]YC-72-AB85 was observed in rat brain. Dynamic μPET brain scans in baseline and blocking conditions in a rhesus monkey indicated Hsp90-specific binding. [11C]YC-72-AB85 is a promising PET tracer for in vivo visualization of Hsp90 in tumor and brain. Clear differences of Hsp90 binding to blood and blood-rich organs were observed in tumor vs control mice. Further, we clearly demonstrate, for the first time, binding to a saturable Hsp90 pool in brain of rats and a rhesus monkey. ",
keywords = "Hsp90, PET, Brain, Neurodegenerative disorders, Nonhuman primate, B16.F10 melanoma",
author = "Koen Vermeulen and Romy Cools and Emmanuelle Briard and Yves Auberson and Joseph Schoepfer and Michel Koole and Christopher Cawthorne and Guy Bormans",
note = "Score=10",
year = "2021",
month = oct,
day = "20",
doi = "10.1021/acschemneuro.1c00508",
language = "English",
volume = "12",
pages = "3915--3927",
journal = "ACS Chemical Neuroscience",
issn = "1948-7193",
publisher = "ACS - American Chemical Society",
number = "20",

}

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TY - JOUR

T1 - Preclinical Evaluation of [ 11 C]YC-72-AB85 for In Vivo Visualization of Heat Shock Protein 90 in Brain and Cancer with Positron Emission Tomography

AU - Vermeulen, Koen

AU - Cools, Romy

AU - Briard, Emmanuelle

AU - Auberson, Yves

AU - Schoepfer, Joseph

AU - Koole, Michel

AU - Cawthorne, Christopher

AU - Bormans, Guy

N1 - Score=10

PY - 2021/10/20

Y1 - 2021/10/20

N2 - Aberrant Hsp90 has been implied in cancer and neurodegenerative disorders. The development of a suitable Hsp90 Positron emission tomography (PET) probe can provide in vivo quantification of the expression levels of Hsp90 as a biomarker for diagnosis and follow-up of cancer and central nervous system (CNS) disease progression. In this respect, [11C]YC-72-AB85 was evaluated as an Hsp90 PET probe in B16.F10 melanoma bearing mice and its brain uptake was determined in rats and nonhuman primate. In vitro binding of [11C]YC-72-AB85 to tissue slices of mouse B16.F10 melanoma, PC3 prostate carcinoma, and rodent brain was evaluated using autoradiography. Biodistribution of [11C]YC-72-AB85 was evaluated in healthy and B16.F10 melanoma mice. In vivo brain uptake was assessed by μPET studies in rats and a rhesus monkey. In vitro binding was deemed Hsp90-specific by blocking studies with heterologous Hsp90 inhibitors onalespib and SNX-0723. Saturable Hsp90 binding was observed in brain, tumor, blood, and blood-rich organs in mice. In combined pretreatment and displacement studies, reversible and Hsp90-specific binding of [11C]YC-72-AB85 was observed in rat brain. Dynamic μPET brain scans in baseline and blocking conditions in a rhesus monkey indicated Hsp90-specific binding. [11C]YC-72-AB85 is a promising PET tracer for in vivo visualization of Hsp90 in tumor and brain. Clear differences of Hsp90 binding to blood and blood-rich organs were observed in tumor vs control mice. Further, we clearly demonstrate, for the first time, binding to a saturable Hsp90 pool in brain of rats and a rhesus monkey.

AB - Aberrant Hsp90 has been implied in cancer and neurodegenerative disorders. The development of a suitable Hsp90 Positron emission tomography (PET) probe can provide in vivo quantification of the expression levels of Hsp90 as a biomarker for diagnosis and follow-up of cancer and central nervous system (CNS) disease progression. In this respect, [11C]YC-72-AB85 was evaluated as an Hsp90 PET probe in B16.F10 melanoma bearing mice and its brain uptake was determined in rats and nonhuman primate. In vitro binding of [11C]YC-72-AB85 to tissue slices of mouse B16.F10 melanoma, PC3 prostate carcinoma, and rodent brain was evaluated using autoradiography. Biodistribution of [11C]YC-72-AB85 was evaluated in healthy and B16.F10 melanoma mice. In vivo brain uptake was assessed by μPET studies in rats and a rhesus monkey. In vitro binding was deemed Hsp90-specific by blocking studies with heterologous Hsp90 inhibitors onalespib and SNX-0723. Saturable Hsp90 binding was observed in brain, tumor, blood, and blood-rich organs in mice. In combined pretreatment and displacement studies, reversible and Hsp90-specific binding of [11C]YC-72-AB85 was observed in rat brain. Dynamic μPET brain scans in baseline and blocking conditions in a rhesus monkey indicated Hsp90-specific binding. [11C]YC-72-AB85 is a promising PET tracer for in vivo visualization of Hsp90 in tumor and brain. Clear differences of Hsp90 binding to blood and blood-rich organs were observed in tumor vs control mice. Further, we clearly demonstrate, for the first time, binding to a saturable Hsp90 pool in brain of rats and a rhesus monkey.

KW - Hsp90

KW - PET

KW - Brain

KW - Neurodegenerative disorders

KW - Nonhuman primate

KW - B16.F10 melanoma

UR - https://ecm.sckcen.be/OTCS/llisapi.dll/overview/48337734

U2 - 10.1021/acschemneuro.1c00508

DO - 10.1021/acschemneuro.1c00508

M3 - Article

VL - 12

SP - 3915

EP - 3927

JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

SN - 1948-7193

IS - 20

M1 - 1c00508

ER -

ID: 7411006