Initial evaluation of Cu-64 labeled PARPi-DOTA PET imaging in mice with mesothelioma

Huang, Tao; Hu, Pengcheng; Banizs, Anna B.; He, Jiang

doi:10.1016/j.bmcl.2017.05.077

Cited by 19 publications

(17 citation statements)

References 21 publications

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“…BAP1 modulates double‐strand DNA damage repair . Cells with BAP1 mutations are more sensitive to both radiation and treatment with olaparib, a PARP inhibitor . There is an ongoing phase 2 study of olaparib in mesothelioma (ClinicalTrials.gov identifier NCT03531840).…”

Section: Treatmentmentioning

confidence: 99%

Mesothelioma: Scientific clues for prevention, diagnosis, and therapy

Carbone

Adusumilli

Alexander

et al. 2019

CA A Cancer J Clinicians

378

488

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Mesothelioma affects mostly older individuals who have been occupationally exposed to asbestos. The global mesothelioma incidence and mortality rates are unknown, because data are not available from developing countries that continue to use large amounts of asbestos. The incidence rate of mesothelioma has decreased in Australia, the United States, and Western Europe, where the use of asbestos was banned or strictly regulated in the 1970s and 1980s, demonstrating the value of these preventive measures. However, in these same countries, the overall number of deaths from mesothelioma has not decreased as the size of the population and the percentage of old people have increased. Moreover, hotspots of mesothelioma may occur when carcinogenic fibers that are present in the environment are disturbed as rural areas are being developed. Novel immunohistochemical and molecular markers have improved the accuracy of diagnosis; however, about 14% (high-resource countries) to 50% (developing countries) of mesothelioma diagnoses are incorrect, resulting in inadequate treatment and complicating epidemiological studies. The discovery that germline BRCA1-asssociated protein 1 (BAP1) mutations cause mesothelioma and other cancers (BAP1 cancer syndrome) elucidated some of the key pathogenic mechanisms, and treatments targeting these molecular mechanisms and/or modulating the immune response are being tested. The role of surgery in pleural mesothelioma is controversial as it is difficult to predict who will benefit from aggressive management, even when local therapies are added to existing or novel systemic treatments. Treatment outcomes are improving, however, for peritoneal mesothelioma. Multidisciplinary international collaboration will be necessary to improve prevention, early detection, and treatment. CA Cancer J Clin 2019;69:402-429.

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Section: Treatmentmentioning

confidence: 99%

Mesothelioma: Scientific clues for prevention, diagnosis, and therapy

Carbone

Adusumilli

Alexander

et al. 2019

CA A Cancer J Clinicians

378

488

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“…A variety of radiolabeled PARP inhibitors has been developed in recent years, all based on either olaparib-like structures (Reiner’s group (17,18,20,42,43), Zmuda et al (48), Huang et al (49), this study) or rucaparib-like structures (Makvandi’s group, Reilly et al (19,23–25)). An excellent review on the subject has been previously published (16).…”

Section: Discussionmentioning

confidence: 97%

PET Imaging of PARP Expression Using ¹⁸F-Olaparib

et al. 2018

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Poly(ADP-ribose) polymerase (PARP) inhibitors are increasingly being studied as cancer drugs, as single agents, or as a part of combination therapies. Imaging of PARP using a radiolabeled inhibitor has been proposed for patient selection, outcome prediction, dose optimization, genotoxic therapy evaluation, and target engagement imaging of novel PARP-targeting agents. Methods: Here, via the copper-mediated 18 F-radiofluorination of aryl boronic esters, we accessed, for the first time (to our knowledge), the 18 F-radiolabeled isotopolog of the Food and Drug Administration–approved PARP inhibitor olaparib. The use of the 18 F-labeled equivalent of olaparib allows direct prediction of the distribution of olaparib, given its exact structural likeness to the native, nonradiolabeled drug. Results: 18 F-olaparib was taken up selectively in vitro in PARP-1–expressing cells. Irradiation increased PARP-1 expression and 18 F-olaparib uptake in a radiation-dose–dependent fashion. PET imaging in mice showed specific uptake of 18 F-olaparib in tumors expressing PARP-1 (3.2% ± 0.36% of the injected dose per gram of tissue in PSN-1 xenografts), correlating linearly with PARP-1 expression. Two hours after irradiation of the tumor (10 Gy), uptake of 18 F-olaparib increased by 70% ( P = 0.025). Conclusion: Taken together, we show that 18 F-olaparib has great potential for noninvasive tumor imaging and monitoring of radiation damage.

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“…18 F-BO Reiner et al, [22] PET, Optical Preclinical 64 Cu-DOTA-PARPi Huang et al, [23] PET, Therapy Preclinical 123 I-MAPI Pirovano et al, [24] SPECT, Therapy Preclinical Rucaparib 18 F-FTT Zhou et al, [25] PET, Optical Clinical Trials NCT03604315, NCT04221061, NCT03492164, NCT03846167, NCT03083288, NCT03334500, NCT02637934, NCT02469129. [28] SPECT, Therapy Preclinical 211 At-MM4 Makvandi et al, [29] Therapy SPECT Preclinical NAD+ 18 F-SUPAR Shuhendler et al, [30] PET, Optical Preclinical…”

Section: Tracer Modality Of Imaging Development Phasementioning

confidence: 99%

“…Moreover, the conjugation of DOTA moiety reduced the binding affinity and thereby the cytotoxicity by 40 times. This would require an increase in the therapeutic dosage, which will in-turn increase systemic toxicity, and consequently limit its theranostic ability [23].…”

Section: βEmitter Theranosticsmentioning

confidence: 99%

“…The radionuclide 64 Cu (T 1/2 = 12.7 h), which emits β - particles for therapy and positrons for PET imaging was conjugated to DOTA-PARPi, derived from olaparib [ 23 ]. This tracer was characterized in mesothelioma models, with biodistribution showing peak tumor uptake at 1 h p.i (3.45 ± 0.47%ID/g), however tumor retention was poor as the tumor-to-muscle ratio at 18 h was ~1.…”

Section: Imaging With Parp-addressing Tracersmentioning

confidence: 99%

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Advancements in PARP1 Targeted Nuclear Imaging and Theranostic Probes

Sankaranarayanan

Kossatz

Weber

et al. 2020

JCM

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The central paradigm of novel therapeutic approaches in cancer therapy is identifying and targeting molecular biomarkers. One such target is the nuclear DNA repair enzyme Poly-(ADP ribose) polymerase 1 (PARP1). Sensitivity to PARP inhibition in certain cancers such as gBRCAmut breast and ovarian cancers has led to its exploitation as a target. The overexpression of PARP1 in several types of cancer further evoked interest in its use as an imaging target. While PARP1-targeted inhibitors have fast developed and approved in this past decade, determination of PARP1 expression might help to predict the response to PARP inhibitor treatment. This has the potential of improving prognosis and moving towards tailored therapy options and/or dosages. This review summarizes the recent pre-clinical advancements in imaging and theranostic PARP1 targeted tracers. To assess PARP1 levels, several imaging probes with fluorescent or beta/gamma emitting radionuclides have been proposed and three have advanced to ongoing clinical evaluation. Apart from its diagnostic value in detection of primary tumors as well as metastases, this shall also help in delivering therapeutic radionuclides to PARP1 overexpressing tumors. Henceforth nuclear medicine has now advanced towards conjugating theranostic radionuclides to PARP1 inhibitors. This paves the way for a future of PARP1-targeted theranostics and personalized therapy.

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Initial evaluation of Cu-64 labeled PARPi-DOTA PET imaging in mice with mesothelioma

Cited by 19 publications

References 21 publications

Mesothelioma: Scientific clues for prevention, diagnosis, and therapy

Mesothelioma: Scientific clues for prevention, diagnosis, and therapy

PET Imaging of PARP Expression Using ¹⁸F-Olaparib

Advancements in PARP1 Targeted Nuclear Imaging and Theranostic Probes

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Initial evaluation of Cu-64 labeled PARPi-DOTA PET imaging in mice with mesothelioma

Cited by 19 publications

References 21 publications

Mesothelioma: Scientific clues for prevention, diagnosis, and therapy

Mesothelioma: Scientific clues for prevention, diagnosis, and therapy

PET Imaging of PARP Expression Using 18F-Olaparib

Advancements in PARP1 Targeted Nuclear Imaging and Theranostic Probes

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PET Imaging of PARP Expression Using ¹⁸F-Olaparib