2. Academic Validation
  3. Evaluation of a simplified radiolabeling method for a PARP inhibitor in an animal model of breast cancer

Evaluation of a simplified radiolabeling method for a PARP inhibitor in an animal model of breast cancer

  • EJNMMI Res. 2025 Apr 29;15(1):50. doi: 10.1186/s13550-025-01236-4.
Chi-Chang Weng 1 2 3,  Chao-Chih Chiang 4,  Yi-Hsiu Chung 5,  Yi-Pei Ho 6,  Yu-Chuan Chang 6 7,  Ing-Tsung Hsiao 6 7,  Robert H Mach 8
Affiliations

Affiliations

  • 1 Department of Medical Imaging and Radiological Sciences, College of Medicine & Healthy Aging Center, Chang Gung University, Taoyuan, Taiwan. ccweng@mail.cgu.edu.tw.
  • 2 Department of Medical Research and Development, Research Division, Chang Gung Memorial Hospital at Linkou, Taoyuan, 333, Taiwan. ccweng@mail.cgu.edu.tw.
  • 3 Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan. ccweng@mail.cgu.edu.tw.
  • 4 Department of Isotope Application Research, National Atomic Research Institute, Taoyuan, Taiwan.
  • 5 Department of Medical Research and Development, Research Division, Chang Gung Memorial Hospital at Linkou, Taoyuan, 333, Taiwan.
  • 6 Department of Medical Imaging and Radiological Sciences, College of Medicine & Healthy Aging Center, Chang Gung University, Taoyuan, Taiwan.
  • 7 Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
  • 8 Division of Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
PMID: 40301197 DOI: 10.1186/s13550-025-01236-4
Abstract

Background: Several poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors were recently approved by the US Food and Drug Administration for use in Cancer treatment. To facilitate the discovery of novel PARP-targeting ligands, a radioiodinated ligand, I-125-KX1, was developed and validated for its specificity to PARP-1; however, its preparation procedure is time-consuming. The present study employed a solid-phase extraction (SPE) method in the radiolabeling procedure of I-123/125-KX1 and evaluated its binding specificity by using receptor binding assays, autoradiography, and in vivo single photon emission computed tomography (SPECT) imaging technique.

Results: Through the incorporation of the SPE purification method as the final step in the radioiodination procedure, the resultant product I-123/125-KX1 exhibited high radiochemical purity (> 99%) and an acceptable radiochemical yield (58.6% for I-123-KX1, 73.3% for I-125-KX1). The binding characteristics of this radiotracer were validated through saturation binding assays conducted on MDA-MB-231 and MCF-7 cells. The Kd values obtained for the tracer (~ 1.0 nM) was consistent with values reported in the literature, and the Bmax values of these two cell lines (2017 ± 178 fmol/mg on MDA-MB-231 vs. 1393 ± 105 fmol/mg on MCF-7) were in line with the results from Western blot analyses. To demonstrate the in vivo imaging ability of I-123-KX1 prepared in this study, an MDA-MB-231 tumor animal model was used and the tracer displayed a suitable uptake on the tumor tissues (6.9 ± 0.8%ID/mL). The binding specificity of the SPE-purified I-125-KX1 was further verified using in vitro autoradiography in conjunction with various PARP inhibitors. Additionally, an anti-PARP-1 immunohistochemistry experiment was conducted, which revealed that the autoradiograms of the radiotracer displayed a similar pattern.

Conclusions: This suggests that the I-123/125-KX1 prepared using the SPE method showed some comparable properties to those from the traditional method, indicating its potential suitability for future radioligand preparation in PARP studies. However, further characterization studies may be needed to confirm its efficacy.

Keywords

Breast cancer; I-123/125-KX1; In vitro autoradiography; In vivo SPECT imaging; PARP; SPE; Saturation binding assay.

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