Take-Away Points
■ Major Focus: To develop a poly(adenosine diphosphate ribose) polymerase (PARP)–targeting radiopharmaceutical for cancer theranostics.
■ Key Result: Single intravenous administration of iodine 123–labeled CC1 ([123I]-CC1, 3 MBq) led to significant tumor growth delay in high PARP1-expressing cancer xenografts without significant toxicity to normal tissues.
■ Impact: [123I]-CC1 shows great potential as an Auger electron–emitting radiopharmaceutical to treat PARP-expressing cancers.
Inhibitors of PARP, a family of enzymes regulating DNA structure and repair, show promise against cancers with defects in homologous recombination of DNA. PARP inhibitors become trapped near DNA, making these inhibitors potential carriers for targeted delivery of ionizing radiation. When labeled with a radionuclide such as 123I, the high ionizing potential and short range of emitted Auger electrons can cause severe DNA damage, effectively killing cancer cells while minimizing harm to surrounding tissues.
In vitro studies showed selective uptake of [123I]-CC1, a radiolabeled PARP inhibitor, in PARP1-expressing models of glioblastoma and breast and pancreatic cancers. Treatment with only 10 Bq of [123I]-CC1 significantly reduced proliferation of cancer cells. SPECT/CT imaging and biodistribution of [123I]-CC1 in a mouse model of pancreatic cancer revealed an optimal tumor-to-muscle signal at 1 hour after injection and hepatobiliary clearance like other fluorine 18–based PARP inhibitors. A single intravenous injection of [123I]-CC1 (3 MBq) significantly inhibited growth of a pancreatic cancer model with high levels of PARP1 without notable toxicity to healthy organs.
This study by Chan et al demonstrates the potential of [123I]-CC1 as a new theranostic agent for cancers with high levels of PARP. Lower doses of [123I]-CC1 could be used for diagnostic SPECT/CT imaging with higher doses for radioligand therapy.
Highlighted Article
Chan CY, Chen Z, Guibbal F, et al. [123I]CC1: A PARP-Targeting, Auger Electron–Emitting Radiopharmaceutical for Radionuclide Therapy of Cancer. J Nucl Med 2023; jnumed.123.265429. doi: https://doi.org/10.2967/jnumed.123.265429
Highlighted Article
- Chan CY , Chen Z , Guibbal F , et al . [123I]CC1: A PARP-Targeting, Auger Electron–Emitting Radiopharmaceutical for Radionuclide Therapy of Cancer . J Nucl Med 2023. ; jnumed.123.265429. doi: 10.2967/jnumed.123.265429 [DOI] [PMC free article] [PubMed] [Google Scholar]