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Preclinical PET Imaging of Tumor Cell Death following Therapy Using Gallium-68-Labeled C2Am.

Published version
Peer-reviewed

Type

Article

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Authors

Bulat, Flaviu 
Attili, Bala 
Solanki, Chandra 
Mendichovszky, Iosif A  ORCID logo  https://orcid.org/0000-0002-3777-2827

Abstract

There is an unmet clinical need for imaging agents capable of detecting early evidence of tumor cell death, since the timing, extent, and distribution of cell death in tumors following treatment can give an indication of treatment outcome. We describe here 68Ga-labeled C2Am, which is a phosphatidylserine-binding protein, for imaging tumor cell death in vivo using positron emission tomography (PET). A one-pot synthesis of 68Ga-C2Am (20 min, 25 °C, >95% radiochemical purity) has been developed, using a NODAGA-maleimide chelator. The binding of 68Ga-C2Am to apoptotic and necrotic tumor cells was assessed in vitro using human breast and colorectal cancer cell lines, and in vivo, using dynamic PET measurements in mice implanted subcutaneously with the colorectal tumor cells and treated with a TRAIL-R2 agonist. 68Ga-C2Am showed predominantly renal clearance and low retention in the liver, spleen, small intestine, and bone and generated a tumor-to-muscle (T/m) ratio of 2.3 ± 0.4, at 2 h post probe administration and at 24 h following treatment. 68Ga-C2Am has the potential to be used in the clinic as a PET tracer for assessing early treatment response in tumors.

Description

Keywords

C2Am, TRAIL-R2, apoptosis, cell death, gallium-68, imaging, positron emission tomography (PET), tumor

Journal Title

Cancers (Basel)

Conference Name

Journal ISSN

2072-6694
2072-6694

Volume Title

15

Publisher

MDPI AG
Sponsorship
Cancer Research UK (C197/A16465)
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