[123I]CC1 - A PARP-Targeting, Auger Electron-Emitting Radiopharmaceutical for Radionuclide Therapy of Cancer

Sep 24, 2026

[123I]CC1 is presented as a PARP-targeting radioligand therapy for cancer, designed to bind near damaged DNA using an Auger electron–emitting radionuclide. PARP-targeted radiolabeled inhibitors exploit the short-range, high-local ionizing potential of Auger electrons to induce complex DNA damage and kill tumor cells while limiting injury to normal tissue. Copper-mediated synthesis was used, and uptake and efficacy were evaluated in multiple cancer cell lines and mouse xenografts, showing selective uptake, reduced clonogenicity, tumor growth inhibition, and minimal normal-tissue toxicity.

LanguageEnglish

CategoryHealthcare

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Pages7

Reading Time18 min

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PARP targeting and rationale

PARP inhibitors and DNA repair trapping

Auger electron properties for localized DNA damage

[123I]CC1 radiopharmaceutical and methods

Radiochemistry synthesis

Cellular uptake and in vitro efficacy

Mouse xenograft tumor uptake and growth inhibition

Results and conclusions

[ 123I]CC1: A PARP-Targeting, Auger Electron–Emitting Radiopharmaceutical for Radionuclide Therapy of Cancer Chung Ying Chan 1, Zijun Chen2, Florian Guibbal1, Gemma Dias 1, Gianluca Destro 1,2, Edward O’Neill 1, Mathew Veal1, Doreen Lau1, Michael Mosley1, Thomas C. Wilson2, Vronique Gouverneur2, and Bart Cornelissen1,3 1MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom; 2Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom; and 3Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands Poly(adenosine diphosphate ribose) polymerase (PARP) has emerged as an effective therapeutic strategy against cancer that targets the DNA damage repair enzyme. PARP-targeting compounds radiolabeled with an Auger electron–emitting radionuclide can be trapped close to damaged DNA in tumor tissue, where high ionizing potential and short range lead Auger electrons to kill cancer cells through the creation of complex DNA damage, with minimal damage to surrounding normal tissue. Here, we report on [123I]CC1, an 123I-labeled PARP inhibitor for radioligand therapy of cancer. Methods: Copper-mediated 123I iododeboronation of a boronic pinacol ester precursor afforded [123I]CC1 . The level and speciﬁcity of cell uptake and the therapeutic efﬁcacy of [123I]CC1 were determined in human breast carcinoma, pancreatic adenocarcinoma, and glioblastoma cells. Tumor uptake and tumor growth inhibition of [123I]CC1 were assessed in mice bearing human cancer xenografts (MDA-MB-231, PSN1, and U87MG). Results: In vitro and in vivo studies showed selective uptake of [123I]CC1 in all models. Signiﬁcantly reduced clonogenicity, a proxy for tumor growth inhibition by ionizing radiation in vivo, was observed in vitro after treatment with as little as 10Bq [123I]CC1 . Biodistribution at 1h after intravenous administration showed PSN1 tumor xenograft uptake of 0.9 60.06 percentage injected dose per gram of tissue. Intravenous administration of a relatively low amount of [123I]CC1 (3 MBq) was able to signiﬁcantly inhibit PSN1 xenograft tumor growth but was less effective in xenografts that expressed less PARP. [123I]CC1 did not cause signiﬁcant toxicity to normal tissues. Conclusion: Taken together, these results show the potential of [123I]CC1 as a radioligand therapy for PARP-expressing cancers. Key Words: PARP; radionuclide therapy; radiopharmaceuticals; 123I; Auger J Nucl Med 2023; 64:1965–1971 DOI: 10.2967/jnumed.123.265429 Poly(adenosine diphosphate ribose) polymerase (PARP) inhibi tors function as competitive inhibitors of the NAD 1 binding pocket of PARP enzymes, a class of DNA damage repair enzymes. They Received Jan. 13, 2023; revision accepted May 24, 2023 . For correspondence or reprints, contact Bart Cornelissen (bart.cornelissen@ [oncology.ox.ac.uk](oncology.ox.ac.uk)). Published online Sep. 28, 2023 . Immediate Open Access: Creative Commons Attribution 4.0 International License (CC BY) allows users to share and adapt with attribution, excluding materials credited to previous publications. License: [https://creativecommons](https://creativecommons). org/licenses/by/4.0/. Details: [http://jnm.snmjournals.org/site/misc/permission](http://jnm.snmjournals.org/site/misc/permission). xhtml. COPYRIGHT 􀀁 2023 by the Society of Nuclear Medicine and Molecular Imaging. inhibit the catalytic function of PARP1 (often called PARP), PARP2, and PARP3, as well as other members of that family of enzymes (1) . Of these, PARP1 is the most abundant and is a critical enzyme for the repair of single-strand DNA damage. PARP inhibitors prevent polyadenoribosylation of target proteins, also stopping autopolyadenoribosylation and thus preventing disengagement from the enzyme from the broken DNA, thereby trapping it (2) . PARP1 expression in tumor tissue tends to be s

FAQs

What is [123I]CC1 and what therapeutic mechanism does it target?

[123I]CC1 is an 123I-labeled PARP inhibitor for radioligand therapy. It targets PARP involved in DNA damage repair and traps near damaged DNA, enabling Auger electrons to generate complex, hard-to-repair DNA damage.

How was [123I]CC1 prepared for evaluation?

[123I]CC1 was produced via copper-mediated 123I iododeboronation of a boronic pinacol ester precursor, followed by determination of cell uptake and specificity in cancer models.

What were the key findings about tumor uptake, efficacy, and safety?

In vitro and in vivo studies showed selective uptake across tested models, with significant reduction in clonogenicity after low activities and tumor growth inhibition in mouse xenografts. [123I]CC1 did not cause significant toxicity to normal tissues.

Sep 24, 2026

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