using-16-18f-fluoro-17-estradiol-pet-to-visualize-estrogen-receptor

Using 16&#945;-[18F]-Fluoro-17&#946;-Estradiol PET to Visualize Estrogen Receptor &#945; Expression in Human Breast Cancer Xenografts in Female Ovariectomized Mice

To demonstrate how estrogen receptor alpha (ER&#945;) positive breast cancer xenografts may be visualized in BALB/c nude mice using ...

Olivia Newton-John Cancer Research Institute

Austin Health

Τhis study aimed to optimize the Zr-radiolabelling of bintrafusp alfa investigational drug product and controls, and perform the in vitro and in vivo characterization of Zr-Df-bintrafusp alfa and Zr-Df-control radioconjugates.

Radiolabelling and preclinical characterization of Zr-Df-radiolabelled bispecific anti-PD-L1/TGF-βRII fusion protein bintrafusp alfa.

Bromodomain and extraterminal (BET) proteins, a family of epigenetic regulators, have emerged as important oncology drug targets. BET proteins have not been targeted for molecular imaging of cancer. Here, we report the development of a novel molecule radiolabelled with positron emitting fluorine-18, [F]BiPET-2, and its  and preclinical evaluation in glioblastoma models.

Bromodomain and extraterminal protein-targeted probe enables tumour visualisation  using positron emission tomography.

Anti-ASCT2 antibody drug conjugate (ADC) MEDI7247 has been under development as a potential anti-cancer therapy for patients with selected relapsed/refractory hematological malignancies and advanced solid tumors by MedImmune. Although promising efficacy was observed in the clinic, pharmacokinetic (PK) analyses observed low exposure of MEDI7247 in phase I hematological patients. To investigate the biodistribution properties of MEDI7247, MEDI7247 and control antibodies were radiolabeled with zirconium-89 and in vitro and in vivo properties characterized.

Preclinical radiolabeling, in vivo biodistribution and positron emission tomography of a novel pyrrolobenzodiazepine (PBD)-based antibody drug conjugate targeting ASCT2.

CI-8993 is a fully human IgG1κ monoclonal antibody (mAb) that binds specifically to immune checkpoint molecule VISTA (V-domain Ig suppressor of T-cell activation). Phase I safety has been established in patients with advanced cancer (NCT02671955). To determine the pharmacokinetics and biodistribution of CI-8993 in patients, we aimed to develop Zr-labelled CI-8993 and validate PET imaging and quantitation in preclinical models prior to a planned human bioimaging trial.

Targeting of immune checkpoint regulator V-domain Ig suppressor of T-cell activation (VISTA) with Zr-labelled CI-8993.

Correction to: Targeting of immune checkpoint regulator V-domain Ig suppressor of T-cell activation (VISTA) with Zr-labelled CI-8993.

Novel radiation sensitizers, including inhibitors targeting DNA damage response, have been developed to enhance the efficacy of anticancer treatments that induce DNA damage in cancer cells. Peposertib, a potent, selective, and orally administered inhibitor of DNA-dependent protein kinase, impedes the nonhomologous end-joining mechanism for DNA double-strand break (DSB) repair. We investigated radioimmunotherapy alone or with peposertib in preclinical models of renal cell carcinoma (RCC) or prostate cancer.  Lu-DOTA-girentuximab (targeting carbonic anhydrase IX) or Lu-DOTA-rosopatamab (targeting prostate-specific membrane antigen) was used to deliver β-radiation to tumors via a single intravenous dose (3 or 6 MBq) in mice bearing SK-RC-52 RCC or LNCaP prostate cancer xenografts, respectively. Peposertib (50 mg/kg daily for 14 d) was administered via oral gavage. Biodistribution and in vivo imaging of Lu-based radioimmunotherapy were performed for both preclinical models. Tumor growth and body weight were monitored until the endpoint. Assessment of DNA damage was performed by measuring DSBs through analysis of γH2AX foci formation in tumor sections.  Ex vivo biodistribution and in vivo SPECT/MRI revealed excellent tumor uptake of each radiopharmaceutical. Mouse body weight was stable in all treatment arms. Peposertib alone did not show a significant antitumor effect. The addition of peposertib to Lu-DOTA-girentuximab showed enhanced antitumor efficacy compared with Lu-DOTA-girentuximab alone in the SK-RC-52 animal model, with a 4 of 4 complete response rate in the Lu-DOTA-girentuximab (6 MBq) plus peposertib arm. Peposertib combined with low-dose Lu-DOTA-girentuximab (3 MBq) demonstrated antitumor activity comparable to Lu-DOTA-girentuximab (6 MBq) monotherapy. In the LNCaP prostate cancer model, the combination of Lu-DOTA-rosopatamab (6 MBq) and peposertib achieved a 3 of 4 complete response rate. Increased DSBs were observed with the addition of peposertib to Lu-based radioimmunotherapy.  The combination of peposertib with Lu-based radioimmunotherapy was well tolerated in preclinical models of RCC and prostate cancer. Our findings suggest a synergistic effect between peposertib and Lu-based radioimmunotherapy, wherein peposertib enhanced the efficacy of radioimmunotherapy. This synergy indicates the potential to reduce the necessary dose of radioimmunotherapy for effective cancer treatment.

DNA-Dependent Protein Kinase Inhibitor Peposertib Enhances Efficacy of Lu-Based Radioimmunotherapy in Preclinical Models of Prostate and Renal Cell Carcinoma.

Article	Year
Radiolabelling and preclinical characterization of Zr-Df-radiolabelled bispecific anti-PD-L1/TGF-βRII fusion protein bintrafusp alfa. European journal of nuclear medicine and molecular imaging\| PubMed ID: 33608805	2021
Bromodomain and extraterminal protein-targeted probe enables tumour visualisation using positron emission tomography. Chemical communications (Cambridge, England)\| PubMed ID: 36809538	2023
Preclinical radiolabeling, in vivo biodistribution and positron emission tomography of a novel pyrrolobenzodiazepine (PBD)-based antibody drug conjugate targeting ASCT2. Nuclear medicine and biology\| PubMed ID: 37473513	2023
Targeting of immune checkpoint regulator V-domain Ig suppressor of T-cell activation (VISTA) with Zr-labelled CI-8993. European journal of nuclear medicine and molecular imaging\| PubMed ID: 39060374	2024
Correction to: Targeting of immune checkpoint regulator V-domain Ig suppressor of T-cell activation (VISTA) with Zr-labelled CI-8993. European journal of nuclear medicine and molecular imaging\| PubMed ID: 39186103	2024
DNA-Dependent Protein Kinase Inhibitor Peposertib Enhances Efficacy of Lu-Based Radioimmunotherapy in Preclinical Models of Prostate and Renal Cell Carcinoma. Journal of nuclear medicine : official publication, Society of Nuclear Medicine\| PubMed ID: 39884775	2025

Alexander McDonald

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