Two Patient Studies of a Companion Diagnostic Immuno-Positron Emission Tomography (PET) Tracer for Measuring Human CA6 Expression in Cancer for Antibody Drug Conjugate (ADC) Therapy

Natarajan, Arutselvan; Srinivas, Shyam; Azevedo, E. Carmen; Greene, Lacey; Bauchet, Anne-Laure; Jouannot, Erwan; Lacoste-Bourgeacq, Anne-Sophie; Guizon, Isabelle; Cohen, Patrick; Naneix, Anne-Laure; Ilovich, Ohad; Cisneros, Jordan; Rupanarayan, Krithika; Chin, Frederick T.; Iagaru, Andrei; Dirbas, Frederick M.; Karam, Amer; Gambhir, Sanjiv S.

doi:10.1177/1536012120939398

Cited by 5 publications

(2 citation statements)

References 24 publications

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“…Additionally, an 89 Zr-labeled anti-MUC1 or CA 15-3 also showed proper performance in vivo ( 37 ). The first clinical study on a Fab targeting carbonic anhydrase 6 (CA6) epitope of MUC1 reported the safety of this probe in an ovarian cancer patient, and the probe correctly reflected the low tumor expression of CA6 observed in IHC ( 370 ).…”

Section: Immunopet In Different Malignanciesmentioning

confidence: 99%

ImmunoPET: Antibody-Based PET Imaging in Solid Tumors

et al. 2022

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Immuno-positron emission tomography (immunoPET) is a molecular imaging modality combining the high sensitivity of PET with the specific targeting ability of monoclonal antibodies. Various radioimmunotracers have been successfully developed to target a broad spectrum of molecules expressed by malignant cells or tumor microenvironments. Only a few are translated into clinical studies and barely into clinical practices. Some drawbacks include slow radioimmunotracer kinetics, high physiologic uptake in lymphoid organs, and heterogeneous activity in tumoral lesions. Measures are taken to overcome the disadvantages, and new tracers are being developed. In this review, we aim to mention the fundamental components of immunoPET imaging, explore the groundbreaking success achieved using this new technique, and review different radioimmunotracers employed in various solid tumors to elaborate on this relatively new imaging modality.

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Section: Immunopet In Different Malignanciesmentioning

confidence: 99%

ImmunoPET: Antibody-Based PET Imaging in Solid Tumors

et al. 2022

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“…The species Cu-ATSM, with ATSM being diacetylbis(4-methyl-3-thiosemicarbazone), is not only under phase 2 of clinical trials for the treatment of rectal cancer (NCT03951337) [25], but has also progressed to phase 2/3 (NCT04082832) for its use against the neurodegenerative disease amyotrophic lateral sclerosis [31]. The complex 64 Cu-DOTA, where DOTA is 2,2 ′ ,2 ′′ ,2 ′′′ -(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetate, reached phase 1 (NCT02708511) for positron emission tomographycomputed tomography use in imaging patients with ovarian and breast cancer [32]. The species Cu-histidinato is at phase 1/2 of the trials for its employment in the treatment of Menkes disease (NCT00001262).…”

Section: Introductionmentioning

confidence: 99%

Experimental and Computational Studies on the Interaction of DNA with Hesperetin Schiff Base CuII Complexes

Pisanu,

Sykula,

Sciortino

et al. 2024

IJMS

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The interactions with calf thymus DNA (CT-DNA) of three Schiff bases formed by the condensation of hesperetin with benzohydrazide (HHSB or L1H3), isoniazid (HIN or L2H3), or thiosemicarbazide (HTSC or L3H3) and their CuII complexes (CuHHSB, CuHIN, and CuHTSC with the general formula [CuLnH2(AcO)]) were evaluated in aqueous solution both experimentally and theoretically. UV–Vis studies indicate that the ligands and complexes exhibit hypochromism, which suggests helical ordering in the DNA helix. The intrinsic binding constants (Kb) of the Cu compounds with CT-DNA, in the range (2.3–9.2) × 106, from CuHTSC to CuHHSB, were higher than other copper-based potential drugs, suggesting that π–π stacking interaction due to the presence of the aromatic rings favors the binding. Thiazole orange (TO) assays confirmed that ligands and Cu complexes displace TO from the DNA binding site, quenching the fluorescence emission. DFT calculations allow for an assessment of the equilibrium between [Cu(LnH2)(AcO)] and [Cu(LnH2)(H2O)]+, the tautomer that binds CuII, amido (am) and not imido (im), and the coordination mode of HTSC (O−, N, S), instead of (O−, N, NH2). The docking studies indicate that the intercalative is preferred over the minor groove binding to CT-DNA with the order [Cu(L1H2am)(AcO)] > [Cu(L2H2am)(AcO)] ≈ TO ≈ L1H3 > [Cu(L3H2am)(AcO)], in line with the experimental Kb constants, obtained from the UV–Vis spectroscopy. Moreover, dockings predict that the binding strength of [Cu(L1H2am)(AcO)] is larger than [Cu(L1H2am)(H2O)]+. Overall, the results suggest that when different enantiomers, tautomers, and donor sets are possible for a metal complex, a computational approach should be recommended to predict the type and strength of binding to DNA and, in general, to macromolecules.

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