Synthesis of a benzoxazinthione derivative of tanaproget and pharmacological evaluation for PET imaging of PR expression

Allott, Louis; Miranda, C.S.; Hayes, Angela; Raynaud, Florence I.; Cawthorne, Christopher; Smith, Graham

doi:10.1186/s41181-018-0054-z

Cited by 21 publications

(30 citation statements)

References 28 publications

(40 reference statements)

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“…In all cases, tracers achieved good tumor visualization in PET images with excellent tumor-to-normal tissue ratios. Moreover, we recently evaluated 225 Ac labeled αMSH derivatives, which also exhibited excellent tumor-to-normal tissue ratios (Ramogida et al 2019 ; Yang et al 2020 ). Knowing the potential of tumor accumulation and internalization, and low uptake in normal tissues, we were interested in labeling an αMSH peptide with 64 Cu to assess the unique theranostic power of 64 Cu.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of DOTA-pyridine chelates for 64Cu coordination and radiolabeling of αMSH peptide

Yang

Gao

McNeil

et al. 2021

EJNMMI radiopharm. chem.

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Background 64Cu is one of the few radioisotopes that can be used for both imaging and therapy, enabling theranostics with identical chemical composition. Development of stable chelators is essential to harness the potential of this isotope, challenged by the presence of endogenous copper chelators. Pyridyl type chelators show good coordination ability with copper, prompting the present study of a series of chelates DOTA-xPy (x = 1–4) that sequentially substitute carboxyl moieties with pyridyl moieties on a DOTA backbone. Results We found that the presence of pyridyl groups significantly increases 64Cu labeling conversion yield, with DOTA-2Py, −3Py and -4Py quantitatively complexing 64Cu at room temperature within 5 min (1 × 10− 4 M). [64Cu]Cu-DOTA-xPy (x = 2–4) exhibited good stability in human serum up to 24 h. When challenged with 1000 eq. of NOTA, no transmetallation was observed for all three 64Cu complexes. DOTA-xPy (x = 1–3) were conjugated to a cyclized α-melanocyte-stimulating hormone (αMSH) peptide by using one of the pendant carboxyl groups as a bifunctional handle. [64Cu]Cu-DOTA-xPy-αMSH retained good serum stability (> 96% in 24 h) and showed high binding affinity (Ki = 2.1–3.7 nM) towards the melanocortin 1 receptor. Conclusion DOTA-xPy (x = 1–3) are promising chelators for 64Cu. Further in vivo evaluation is necessary to assess the full potential of these chelators as a tool to enable further theranostic radiopharmaceutical development.

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Section: Introductionmentioning

confidence: 99%

Synthesis of DOTA-pyridine chelates for 64Cu coordination and radiolabeling of αMSH peptide

Yang

Gao

McNeil

et al. 2021

EJNMMI radiopharm. chem.

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“…Several approaches have been applied on the targeting of CAF-related surface markers, such as FAP and α-SMA [ 71 ], since they are highly expressed in a number of tumour tissues, including pancreatic, lung, and breast cancer [ 72 ]. Some of these novel approaches include the use of monoclonal antibodies (mAb), small molecules [ 73 ], or chimeric antigen receptor (CAR) T-cells [ 74 ]; immunotherapy [ 75 ]; targeting of metabolism; conversion strategies.…”

Section: Targeting Cafs As An Approach To Anti-cancer Therapymentioning

confidence: 99%

Cancer-Associated Fibroblasts as Players in Cancer Development and Progression and Their Role in Targeted Radionuclide Imaging and Therapy

Koustoulidou

Hoorens

Dalm

et al. 2021

Cancers

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Cancer Associated Fibroblasts (CAFs) form a major component of the tumour microenvironment, they have a complex origin and execute diverse functions in tumour development and progression. As such, CAFs constitute an attractive target for novel therapeutic interventions that will aid both diagnosis and treatment of various cancers. There are, however, a few limitations in reaching successful translation of CAF targeted interventions from bench to bedside. Several approaches targeting CAFs have been investigated so far and a few CAF-targeting tracers have successfully been developed and applied. This includes tracers targeting Fibroblast Activation Protein (FAP) on CAFs. A number of FAP-targeting tracers have shown great promise in the clinic. In this review, we summarize our current knowledge of the functional heterogeneity and biology of CAFs in cancer. Moreover, we highlight the latest developments towards theranostic applications that will help tumour characterization, radioligand therapy and staging in cancers with a distinct CAF population.

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“…They can also kill cancer cells by damaging the cell membrane and kill non-directly targeted cells through a cross-dose or bystander effect [ 9 ]. Clinical studies with Auger electrons for cancer therapy have been limited; however, some encouraging results were obtained using [ 111 In]In-DTPA-octreotide in rats with pancreatic tumors, [ 125 I]I-IUdR where tumor remissions were achieved, and [ 125 I]I-mAb 425 where the survival of glioblastoma patients improved [ 5 , 10 , 11 ]. However, it has also been determined that some Auger electron emitting compounds, such as [ 123 I]I-IUdR and [ 125 I]I-IUdR only kill cells in the S-phase of the cell cycle, highlighting a potential treatment limitation [ 12 ].…”

Section: Selecting Radionuclides For Radiotherapymentioning

confidence: 99%

Targeted Alpha Therapy: Progress in Radionuclide Production, Radiochemistry, and Applications

2020

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This review outlines the accomplishments and potential developments of targeted alpha (α) particle therapy (TAT). It discusses the therapeutic advantages of the short and highly ionizing path of α-particle emissions; the ability of TAT to complement and provide superior efficacy over existing forms of radiotherapy; the physical decay properties and radiochemistry of common α-emitters, including 225Ac, 213Bi, 224Ra, 212Pb, 227Th, 223Ra, 211At, and 149Tb; the production techniques and proper handling of α-emitters in a radiopharmacy; recent preclinical developments; ongoing and completed clinical trials; and an outlook on the future of TAT.

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Synthesis of a benzoxazinthione derivative of tanaproget and pharmacological evaluation for PET imaging of PR expression

Cited by 21 publications

References 28 publications

Synthesis of DOTA-pyridine chelates for 64Cu coordination and radiolabeling of αMSH peptide

Synthesis of DOTA-pyridine chelates for 64Cu coordination and radiolabeling of αMSH peptide

Cancer-Associated Fibroblasts as Players in Cancer Development and Progression and Their Role in Targeted Radionuclide Imaging and Therapy

Targeted Alpha Therapy: Progress in Radionuclide Production, Radiochemistry, and Applications

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