Imaging PARP with [18F]rucaparib in pancreatic cancer models.

PURPOSE: Rucaparib, an FDA-approved PARP inhibitor, is used as a single agent in maintenance therapy to provide promising treatment efficacy with an acceptable safety profile in various types of BRCA-mutated cancers. However, not all patients receive the same benefit from rucaparib-maintenance therapy. A predictive biomarker to help with patient selection for rucaparib treatment and predict clinical benefit is therefore warranted. With this aim, we developed [18F]rucaparib, an 18F-labelled isotopologue of rucaparib, and employed it as a PARP-targeting agent for cancer imaging with PET. Here, we report the in vitro and in vivo evaluation of [18F]rucaparib in human pancreatic cancer models. METHOD: We incorporated the positron-emitting 18F isotope into rucaparib, enabling its use as a PET imaging agent. [18F]rucaparib binds to the DNA damage repair enzyme, PARP, allowing direct visualisation and measurement of PARP in cancerous models before and after PARP inhibition or other genotoxic cancer therapies, providing critical information for cancer diagnosis and therapy. Proof-of-concept evaluations were determined in pancreatic cancer models. RESULTS: Uptake of [18F]rucaparib was found to be mainly dependent on PARP1 expression. Induction of DNA damage increased PARP expression, thereby increasing uptake of [18F]rucaparib. In vivo studies revealed relatively fast blood clearance of [18F]rucaparib in PSN1 tumour-bearing mice, with a tumour uptake of 5.5 ± 0.5%ID/g (1 h after i.v. administration). In vitro and in vivo studies showed significant reduction of [18F]rucaparib uptake by addition of different PARP inhibitors, indicating PARP-selective binding. CONCLUSION: Taken together, we demonstrate the potential of [18F]rucaparib as a non-invasive PARP-targeting imaging agent for pancreatic cancers.

18F-Trifluoromethanesulfinate Enables Direct C-H 18F-Trifluoromethylation of Native Aromatic Residues in Peptides.

18F labeling strategies for unmodified peptides with [18F]fluoride require 18F-labeled prosthetics for bioconjugation more often with cysteine thiols or lysine amines. Here we explore selective radical chemistry to target aromatic residues applying C-H 18F-trifluoromethylation. We report a one-step route to [18F]CF3SO2NH4 from [18F]fluoride and its application to direct [18F]CF3 incorporation at tryptophan or tyrosine residues using unmodified peptides as complex as recombinant human insulin. The fully automated radiosynthesis of octreotide[Trp(2-CF218F)] enables in vivo positron emission tomography imaging.

Vessel wall enhancement of intracranial aneurysms: fact or artifact?

OBJECTIVE: For patients with subarachnoid hemorrhage (SAH) and multiple intracranial aneurysms, it is often challenging to identify the ruptured aneurysm. Some investigators have asserted that vessel wall imaging (VWI) can be used to identify the ruptured aneurysm since wall enhancement after contrast agent injection is presumably related to inflammation in unstable and ruptured aneurysms. The aim of this study was to determine whether additional factors contribute to aneurysm wall enhancement by assessing imaging data in a series of patients. METHODS: Patients with symptoms of SAH who subsequently underwent VWI in the period between January 2017 and September 2018 were eligible for study inclusion. Three-dimensional turbo spin-echo sequences with motion-sensitized driven-equilibrium preparation pulses were acquired using a 3-T MRI scanner to visualize the aneurysm wall. Identification of the ruptured aneurysm was based on aneurysm characteristics and hemorrhage distributions on MRI. Complementary imaging data (CT, DSA, MRI) were used to assess potential underlying enhancement mechanisms. Additionally, aneurysm luminal diameter measurements on MRA were compared with those on contrast-enhanced VWI to assess the intraluminal contribution to aneurysm enhancement. RESULTS: Six patients with 14 aneurysms were included in this series. The mean aneurysm size was 5.8 mm (range 1.1-16.9 mm). A total of 10 aneurysms showed enhancement on VWI; 5 ruptured aneurysms showed enhancement, and 1 unruptured but symptomatic aneurysm showed enhancement on VWI and ruptured 1 day later. Four unruptured aneurysms showed enhancement. In 6 (60%) of the 10 enhanced aneurysms, intraluminal diameters appeared notably smaller (≥ 0.8 mm smaller) on contrast-enhanced VWI compared to their appearance on multiple overlapping thin slab acquisition time of flight (MOTSA-TOF) MRA and/or precontrast VWI, suggesting that enhancement was at least partially in the aneurysm lumen itself. CONCLUSIONS: Several factors other than the hypothesized inflammatory response contribute to aneurysm wall enhancement. In 60% of the cases in this study, enhancement was at least partially caused by slow intraaneurysmal flow, leading to pseudo-enhancement of the aneurysm wall. Notwithstanding, there seems to be clinical value in differentiating ruptured from unruptured aneurysms using VWI, but the hypothesis that we image the inflammatory cell infiltration in the aneurysm wall is not yet confirmed.

Insufficient slow-flow suppression mimicking aneurysm wall enhancement in magnetic resonance vessel wall imaging: a phantom study.

OBJECTIVE: MR vessel wall imaging (VWI) is increasingly performed in clinical settings to support treatment decision-making regarding intracranial aneurysms. Aneurysm wall enhancement after contrast agent injection is expected to be related to aneurysm instability and rupture status. However, the authors hypothesize that slow-flow artifacts mimic aneurysm wall enhancement. Therefore, in this phantom study they assess the effect of slow flow on wall-like enhancement by using different MR VWI techniques. METHODS: The authors developed an MR-compatible aneurysm phantom model, which was connected to a pump to enable pulsatile inflow conditions. For VWI, 3D turbo spin echo sequences-both with and without motion-sensitized driven equilibrium (MSDE) and delay alternating with nutation for tailored excitation (DANTE) preparation pulses-were performed using a 3-T MR scanner. VWI was acquired both before and after Gd contrast agent administration by using two different pulsatile inflow conditions (2.5 ml/sec peak flow at 77 and 48 beats per minute). The intraluminal signal intensity along the aneurysm wall was analyzed to assess the performance of slow-flow suppression. RESULTS: The authors observed wall-like enhancement after contrast agent injection, especially in low pump rate settings. Preparation pulses, in particular the DANTE technique, improved the performance of slow-flow suppression. CONCLUSIONS: Near-wall slow flow mimics wall enhancement in VWI protocols. Therefore, VWI should be carefully interpreted. Preparation pulses improve slow-flow suppression, and therefore the authors encourage further development and clinical implementation of these techniques.

Intracranial aneurysm growth: consistency of morphological changes.

OBJECTIVE: Previous studies have shown a relation between growth and rupture of intracranial aneurysms. Additionally, several morphological characteristics are frequently measured to estimate rupture risk. Little is known about how the rupture risk is associated with morphological characteristic changes during growth. The aim of this study was to provide insights into how morphological characteristics, associated with rupture, change during an aneurysm's growth. METHODS: The authors retrospectively identified patients with longitudinal MRA images of unruptured growing aneurysms. The MRA images had an in-plane resolution of 0.2-0.5 mm and a slice thickness of 0.2-0.75 mm. Therefore, growth was defined as an increase of at least 0.5 mm in two directions or 1 mm in one direction. Using the MRA images, the authors semiautomatically segmented the aneurysm and the perianeurysmal vasculature. Twelve morphological characteristics were automatically measured. These characteristics were related to size (diameter, height, width, neck diameter, volume, surface area, aspect ratio, height-width ratio, and bottleneck factor) and shape (ellipticity index, nonsphericity index, and undulation index) of the aneurysm. Morphological characteristics before and after growth were compared using the Wilcoxon signed-rank test. RESULTS: The authors included 31 patients with 38 growing aneurysms. The aneurysms' growth was detected after a mean of 218 weeks (range 23-567 weeks). A significant increase was seen in all size-related characteristics, and the bottleneck factor also significantly increased (from a median of 1.00 [IQR 0.85-1.04] to 1.03 [IQR 0.93-1.18]), while the ellipticity index decreased (from a median of 0.26 [IQR 0.25-0.28] to 0.25 [IQR 0.24-0.26]). The changes in size ratios and shape indices varied largely among patients. Larger aneurysms more often showed an increase in shape ratios. CONCLUSIONS: Although aneurysm growth, size-related characteristics, bottleneck factor, and ellipticity index changed significantly during growth, most size ratios and shape indices showed inconsistent changes among aneurysms. This suggests that, for an accurate rupture prediction, morphological parameters need to be reassessed after growth.

Translational molecular imaging in exocrine pancreatic cancer.

Effective treatment for pancreatic cancer remains challenging, particularly the treatment of pancreatic ductal adenocarcinoma (PDAC), which makes up more than 95% of all pancreatic cancers. Late diagnosis and failure of chemotherapy and radiotherapy are all too common, and many patients die soon after diagnosis. Here, we make the case for the increased use of molecular imaging in PDAC preclinical research and in patient management.

Imaging the DNA damage response with PET and SPECT.

DNA integrity is constantly challenged by endogenous and exogenous factors that can alter the DNA sequence, leading to mutagenesis, aberrant transcriptional activity, and cytotoxicity. Left unrepaired, damaged DNA can ultimately lead to the development of cancer. To overcome this threat, a series of complex mechanisms collectively known as the DNA damage response (DDR) are able to detect the various types of DNA damage that can occur and stimulate the appropriate repair process. Each DNA damage repair pathway leads to the recruitment, upregulation, or activation of specific proteins within the nucleus, which, in some cases, can represent attractive targets for molecular imaging. Given the well-established involvement of DDR during tumorigenesis and cancer therapy, the ability to monitor these repair processes non-invasively using nuclear imaging techniques may facilitate the earlier detection of cancer and may also assist in monitoring response to DNA damaging treatment. This review article aims to provide an overview of recent efforts to develop PET and SPECT radiotracers for imaging of DNA damage repair proteins.

In Vivo Pretargeted Imaging of HER2 and TAG-72 Expression Using the HaloTag Enzyme.

A novel pretargeted SPECT imaging strategy based on the HaloTag enzyme has been evaluated for the first time in a living system. To determine the efficacy of this approach, two clinically relevant cancer biomarkers, HER2 and TAG-72, were selected to represent models of internalizing and noninternalizing antigens, respectively. In MDA-MB-231/H2N (HER2-expressing) and LS174T (TAG-72-expressing) xenograft tumors in mice, pretargeting experiments were performed in which HaloTag-conjugated derivatives of the antibodies trastuzumab (anti-HER2) or CC49 (anti-TAG-72) were utilized as primary agents, and the small molecule HaloTag ligands 111In-HTL-1, -2, and -3 were evaluated as secondary agents. While this approach was not sufficiently sensitive to detect the internalizing HER2 antigen, pretargeting experiments involving the most optimal secondary agent, 111In-HTL-3, were successful in detecting the noninternalizing antigen TAG-72 and provided high-contrast SPECT images at 4 and 24 h postinjection.

PET imaging of DNA damage using (89)Zr-labelled anti-γH2AX-TAT immunoconjugates.

PURPOSE: The efficacy of most anticancer treatments, including radiotherapy, depends on an ability to cause DNA double-strand breaks (DSBs). Very early during the DNA damage signalling process, the histone isoform H2AX is phosphorylated to form γH2AX. With the aim of positron emission tomography (PET) imaging of DSBs, we synthesized a (89)Zr-labelled anti-γH2AX antibody, modified with the cell-penetrating peptide, TAT, which includes a nuclear localization sequence. METHODS: (89)Zr-anti-γH2AX-TAT was synthesized using EDC/NHS chemistry for TAT peptide linkage. Desferrioxamine conjugation allowed labelling with (89)Zr. Uptake and retention of (89)Zr-anti-γH2AX-TAT was evaluated in the breast adenocarcinoma cell line MDA-MB-468 in vitro or as xenografts in athymic mice. External beam irradiation was used to induce DSBs and expression of γH2AX. Since (89)Zr emits ionizing radiation, detailed radiobiological measurements were included to ensure (89)Zr-anti-γH2AX-TAT itself does not cause any additional DSBs. RESULTS: Uptake of (89)Zr-anti-γH2AX-TAT was similar to previous results using (111)In-anti-γH2AX-TAT. Retention of (89)Zr-anti-γH2AX-TAT was eightfold higher at 1 h post irradiation, in cells expressing γH2AX, compared to non-irradiated cells or to non-specific IgG control. PET imaging of mice showed higher uptake of (89)Zr-anti-γH2AX-TAT in irradiated xenografts, compared to non-irradiated or non-specific controls (12.1 ± 1.6 vs 5.2 ± 1.9 and 5.1 ± 0.8%ID/g, respectively; p < 0.0001). The mean absorbed dose to the nucleus of cells taking up (89)Zr-anti-γH2AX-TAT was twofold lower compared to (111)In-anti-γH2AX-TAT. Additional exposure of neither irradiated nor non-irradiated cells nor tissues to (89)Zr-anti-γH2AX-TAT resulted in any significant changes in the number of observable DNA DSBs, γH2AX foci or clonogenic survival. CONCLUSION: (89)Zr-anti-γH2AX-TAT allows PET imaging of DNA DSBs in a tumour xenograft mouse model.

Green light may improve diagnostic accuracy of nailfold capillaroscopy with a simple digital videomicroscope.

Nailfold capillaroscopy is a non-invasive and safe technique for the analysis of microangiopathologies. Imaging quality of widely used simple videomicroscopes is poor. The use of green illumination instead of the commonly used white light may improve contrast. The aim of the study was to compare the effect of green illumination with white illumination, regarding capillary density, the number of microangiopathologies, and sensitivity and specificity for systemic sclerosis. Five rheumatologists have evaluated 80 images; 40 images acquired with green light, and 40 images acquired with white light. A larger number of microangiopathologies were found in images acquired with green light than in images acquired with white light. This results in slightly higher sensitivity with green light in comparison with white light, without reducing the specificity. These findings suggest that green instead of white illumination may facilitate evaluation of capillaroscopic images obtained with a low-cost digital videomicroscope.

Imaging the inside of a tumour: a review of radionuclide imaging and theranostics targeting intracellular epitopes.

Molecular imaging of tumour tissue focusses mainly on extracellular epitopes such as tumour angiogenesis or signal transduction receptors expressed on the cell membrane. However, most biological processes that define tumour phenotype occur within the cell. In this mini-review, an overview is given of the various techniques to interrogate intracellular events using molecular imaging with radiolabelled compounds. Additionally, similar targeting techniques can be employed for radionuclide therapy using Auger electron emitters, and recent advances in Auger electron therapy are discussed.

A novel method to perform morphological measurements on three-dimensional (3D) models of the calcaneus based on computed tomography (CT)-imaging.

Background: While current preoperative and postoperative assessment of the fractured and surgically reconstructed calcaneus relies on computed tomography (CT)-imaging, there are no established methods to quantify calcaneus morphology on CT-images. This study aims to develop a semi-automated method for morphological measurements of the calcaneus on three-dimensional (3D) models derived from CT-imaging. Methods: Using CT data, 3D models were created from healthy, fractured, and surgically reconstructed calcanei. Böhler's angle (BA) and Critical angle of Gissane (CAG) were measured on conventional lateral radiographs and corresponding 3D CT reconstructions using a novel point-based method with semi-automatic landmark placement by three observers. Intraobserver and interobserver reliability scores were calculated using intra-class correlation coefficient (ICC). In addition, consensus among observers was calculated for a maximal allowable discrepancy of 5 and 10 degrees for both methods. Results: Imaging data from 119 feet were obtained (40 healthy, 39 fractured, 40 reconstructed). Semi-automated measurements on 3D models of BA and CAG showed excellent reliability (ICC: 0.87-1.00). The manual measurements on conventional radiographs had a poor-to-excellent reliability (ICC: 0.22-0.96). In addition, the percentage of consensus among observers was much higher for the 3D method when compared to conventional two-dimensional (2D) measurements. Conclusions: The proposed method enables reliable and reproducible quantification of calcaneus morphology in 3D models of healthy, fractured and reconstructed calcanei.

Subcutaneous tumor volume measurement in the awake, manually restrained mouse using MRI.

PURPOSE: To describe a combination of techniques using the excellent volumetric capacities of magnetic resonance imaging (MRI) while avoiding anesthesia and maintaining high-throughput capability for tumor volume measurement in the awake mouse. This approach presents an alternative to calipers which, although cheap, fast, and easy to use, introduce many biases for tumor volume estimation. MATERIALS AND METHODS: The murine CaNT subcutaneous xenograft model was used. A quiet and modestly T2-weighted spin-echo scan was acquired at 4.7T (TE = 15 msec, TR = 1100 msec, 0.5 mm isotropic resolution) while the awake mouse was held by hand in the magnet. This method was compared to standard MR in the anesthetized mouse and caliper measurements. RESULTS: The combination of techniques used allows rapid, accurate, and reproducible measurement of subcutaneous tumor volumes in awake mice. It is less sensitive to both intra- and interoperator-derived biases and avoids confounds from the compliance of the fat and skin around the tumor, as well as from the tumor itself. Moreover, the data remain available for retrieval and scrutiny and reanalysis. CONCLUSION: Rapid, accurate, and precise tumor volumetry can be performed in the awake mouse by handheld positioned MR.

Second Symposium of the European Working Group on the Radiobiology of Molecular Radionuclide Therapy.

Molecular radionuclide therapy is a relatively novel anticancer treatment option using radiolabeled, tumor-specific vectors. On binding of these vectors to cancer cells, radioactive decay induces DNA damage and other effects, leading to cancer cell death. Treatments, such as with [177Lu]Lu-octreotate for neuroendocrine tumors and [177Lu]Lu-PSMA for prostate cancer, are now being implemented into routine clinical practice around the world. Nonetheless, research into the underlying radiobiologic effects of these treatments is essential to further improve them or formulate new ones. The purpose of the European Working Group on the Radiobiology of Molecular Radiotherapy is to promote knowledge, investment, and networking in this area. This report summarizes recent research and insights presented at the second International Workshop on Radiobiology of Molecular Radiotherapy, held in London, U.K., on March 13 and 14, 2023. The symposium was organized by members of the Cancer Research U.K. RadNet City of London and the European Working Group on the Radiobiology of Molecular Radiotherapy.

Imaging DNA damage response by γH2AX in vivo predicts treatment response to Lutetium-177 radioligand therapy and suggests senescence as a therapeutically desirable outcome.

Rationale: An effective absorbed dose response relationship is yet to be established for Lutetium-177 based radionuclide therapies such as 177Lu-DOTATATE and 177Lu-PSMA. The inherent biological heterogeneity of neuroendocrine and prostate cancers may make the prospect of establishing cohort-based dose-response relationships unobtainable. Instead, an individual-based approach, monitoring the dose-response within each tumor could provide the necessary metric to monitor treatment efficacy. Methods: We developed a dual isotope SPECT imaging strategy to monitor the change over time in the relationship between 177Lu-DOTATATE and 111In-anti-γH2AX-TAT, a modified radiolabelled antibody that allows imaging of DNA double strand breaks, in mice bearing rat pancreatic cancer xenografts. The dynamics of γH2AX foci, apoptosis and senescence following exposure to 177Lu-DOTATATE was further investigated in vitro and in ex vivo tumor sections. Results: The change in slope of the 111In-anti-γH2AX-TAT to 177Lu signal between days 5 and 7 was found to be highly predictive of survival (r = 0.955, P < 0.0001). This pivotal timeframe was investigated further in vitro: clonogenic survival correlated with the number of γH2AX foci at day 6 (r = -0.995, P < 0.0005). While there was evidence of continuously low levels of apoptosis, delayed induction of senescence in vitro appeared to better account for the γH2AX response to 177Lu. The induction of senescence was further investigated by ex vivo analysis and corresponded with sustained retention of 177Lu within tumor regions. Conclusions: Dual isotope SPECT imaging can provide individualized tumor dose-responses that can be used to predict lutetium-177 treatment efficacy. This bio-dosimeter metric appears to be dependent upon the extent of senescence induction and suggests an integral role that senescence plays in lutetium-177 treatment efficacy.

Marshalling the Potential of Auger Electron Radiopharmaceutical Therapy.

Auger electron (AE) radiopharmaceutical therapy (RPT) may have the same therapeutic efficacy as α-particles for oncologic small disease, with lower risks of normal-tissue toxicity. The seeds of using AE emitters for RPT were planted several decades ago. Much knowledge has been gathered about the potency of the biologic effects caused by the intense shower of these low-energy AEs. Given their short range, AEs deposit much of their energy in the immediate vicinity of their site of decay. However, the promise of AE RPT has not yet been realized, with few agents evaluated in clinical trials and none becoming part of routine treatment so far. Instigated by the 2022 "Technical Meeting on Auger Electron Emitters for Radiopharmaceutical Developments" at the International Atomic Energy Agency, this review presents the current status of AE RPT based on the discussions by experts in the field. A scoring system was applied to illustrate hurdles in the development of AE RPT, and we present a selected list of well-studied and emerging AE-emitting radionuclides. Based on the number of AEs and other emissions, physical half-life, radionuclide production, radiochemical approaches, dosimetry, and vector availability, recommendations are put forward to enhance and impact future efforts in AE RPT research.

A radioiodinated rucaparib analogue as an Auger electron emitter for cancer therapy.

INTRODUCTION: Radioligand therapy (RLT) is an expanding field that has shown great potential in the fight against cancer. Radionuclides that can be carried by selective ligands such as antibodies, peptides, and small molecules targeting cancerous cells have demonstrated a clear improvement in the move towards precision medicine. Poly (ADP-ribose) polymerase (PARP) is a family of enzymes involved in DNA damage repair signalling pathway, with PARP inhibitors olaparib, talazoparib, niraparib, veliparib, and rucaparib having FDA approval for cancer therapy in routine clinical use. Based on our previous work with the radiolabelled PARP inhibitor [18F]rucaparib, we replaced the fluorine-18 moiety, used for PET imaging, with iodine-123, a radionuclide used for SPECT imaging and Auger electron therapy, resulting in 8-[123I]iodo-5-(4-((methylamino)methyl)phenyl)-2,3,4,6-tetrahydro-1H-azepino[5,4,3-cd]indol-1-one, ([123I]GD1), as a potential radiopharmaceutical for RLT. METHODS: [123I]GD1 was synthesized via copper-mediated radioiodination from a selected boronic esters precursor. In vitro uptake, retention, blocking, and effects on clonogenic survival with [123I]GD1 treatment were tested in a panel of cancer cell lines. Enzymatic inhibition of PARP by GD1 was also tested in a cell-free system. The biodistribution of [123I]GD1 was investigated by SPECT/CT in mice following intravenous administration. RESULTS: Cell-free enzymatic inhibition and in vitro blocking experiments confirmed a modest ability of GD1 to inhibit PARP-1, IC50 = 239 nM. In vitro uptake of [123I]GD1 in different cell lines was dose dependent, and radiolabelled compound was retained in cells for >2 h. Significantly reduced clonogenic survival was observed in vitro after exposure of cells for 1 h with as low as 50 kBq of [123I]GD1. The biodistribution of [123I]GD1 was further characterized in vivo showing both renal and hepatobiliary clearance pathways with a biphasic blood clearance. CONCLUSION: We present the development of a new theragnostic agent based on the rucaparib scaffold and its evaluation in in vitro and in vivo models. The data reported show that [123I]GD1 may have potential to be used as a theragnostic agent.

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

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 10 Bq [123I]CC1. Biodistribution at 1 h after intravenous administration showed PSN1 tumor xenograft uptake of 0.9 ± 0.06 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.