The efficiency of 18F labelling of a prostate specific membrane antigen ligand via strain-promoted azide–alkyne reaction: reaction speed versus hydrophilicity

Wang, Mengzhe; McNitt, Christopher D.; Wang, Hui; Ma, Xiaofen; Scarry, Sarah M.; Wu, Zhanhong; Popik, Vladimir V.; Li, Zibo

doi:10.1039/c8cc03999b

Cited by 9 publications

(22 citation statements)

References 30 publications

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“…Starting materials 2a and 2b are commercially available. Starting materials 2c , 3 , 5 , 9 , 12 , and reagent B 10 H 12 (MeCN) 2 were obtained following known literature procedures. Briefly, compound 3 was reacted with B 10 H 12 (MeCN) 2 followed by deprotection to generate intermediate 2d.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Initial Biological Evaluation of Boron-Containing Prostate-Specific Membrane Antigen Ligands for Treatment of Prostate Cancer Using Boron Neutron Capture Therapy

et al. 2019

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Boron neutron capture therapy (BNCT) is a therapeutic modality which has been used for the treatment of cancers, including brain and head and neck tumors. For effective treatment via BNCT, efficient and selective delivery of a high boron dose to cancer cells is needed. Prostate-specific membrane antigen (PSMA) is a target for prostate cancer imaging and drug delivery. In this study, we conjugated boronic acid or carborane functional groups to a well-established PSMA inhibitor scaffold to deliver boron to prostate cancer cells and prostate tumor xenograft models. Eight boron-containing PSMA inhibitors were synthesized. All of these compounds showed a strong binding affinity to PSMA in a competition radioligand binding assay (IC50 from 555.7 to 20.3 nM). Three selected compounds 1a, 1d, and 1f were administered to mice, and their in vivo blocking of 68Ga-PSMA-11 uptake was demonstrated through a positron emission tomography (PET) imaging and biodistribution experiment. Biodistribution analysis demonstrated boron uptake of 4–7 μg/g in 22Rv1 prostate xenograft tumors and similar tumor/muscle ratios compared to the ratio for the most commonly used BNCT compound, 4-borono-l-phenylalanine (BPA). Taken together, these data suggest a potential role for PSMA targeted BNCT agents in prostate cancer therapy following suitable optimization.

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Section: Resultsmentioning

confidence: 99%

Synthesis and Initial Biological Evaluation of Boron-Containing Prostate-Specific Membrane Antigen Ligands for Treatment of Prostate Cancer Using Boron Neutron Capture Therapy

et al. 2019

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“…F-BCN-PSMA, on the other hand, showed visible uptake in LnCap tumors but undetectable uptake in NTR1_positive/ PSMA_negative PC-3 tumors (Figure 5) similar to a previous report. 28 18 F-BCN-NT-PSMA was mainly cleared through the renal pathway, similar to the two monomers. However, the absolute kidney uptake number was significantly reduced for the heterodimer, compared with PSMA monomer in both tumor models, which could be partially caused by the decreased water solubility (the logP value of 18 F-BCN-NT-PSMA and 18 F-BCN-PSMA was −1.06 ± 0.02 and −1.90 ± 0.01, respectively).…”

Section: ■ Resultsmentioning

confidence: 85%

“…In brief, 18 F-BCN was synthesized in 8% isolation yield based on our previous report. 28 Through strain-promoted azide alkyne click reaction, the radiolabeling of the N 3 -NT-PSMA heterodimer and N 3 -NT monomers is performed and the decay-corrected isolation yield was 39.5% and 34.1%, respectively, with radiochemical purity over 99% (Figure 1). The purity was double confirmed by isocratic HPLC using 32% acetonitrile/ water 0.1% TFA as mobile phase (Figures S4 and S5).…”

Section: ■ Resultsmentioning

confidence: 93%

“…The 18 F-BCN-N3-PSMA was prepared as previously reported. 28 The logP value of 18 F-BCN-NT-PSMA and 18 F-BCN-NT was −1.06 ± 0.02 and −0.30 ± 0.02, respectively. The logP of 18 F-BCN-PSMA was −1.90 ± 0.01, which was consistent with the previously reported value.…”

Section: ■ Resultsmentioning

confidence: 98%

“…The logP of 18 F-BCN-PSMA was −1.90 ± 0.01, which was consistent with the previously reported value. 28 In Vitro Cell Binding Assay. The NTR1 binding affinity of 19 F-BCN-NT-PSMA and 19 F-BCN-NT was evaluated in PC-3 cells and compared with the parent peptide NT (8−13).…”

Section: ■ Resultsmentioning

confidence: 99%

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Development of Bispecific NT-PSMA Heterodimer for Prostate Cancer Imaging: A Potential Approach to Address Tumor Heterogeneity

Wang

et al. 2019

Bioconjugate Chem.

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Prostate cancer is a heterogeneous disease with a poor survival rate at late stage. In this report, a dual targeting PET agent was developed to partially address the tumor heterogeneity issue. The heterodimer F-BCN-PSMA-NT was designed to target PSMA and neurotensin receptor1 (NTR1), both of which have demonstrated great potential in prostate cancer management. The heterodimer was synthesized through the conjugation of Glu-urea-lys(Ahx) (PSMA targeting motif) and NT20.3 (NTR1 targeting motif) to a symmetric trifunctional linker, bearing an azide group for further modification. Radio-labeling was performed using strain promoted azide−alkyne click reaction with high yield. Cell based assays suggested that F-BCN-PSMA-NT has comparable or only slightly reduced binding affinity with the corresponding monomers. Small animal PET clearly demonstrated that the heterodimer probe has prominent uptake not only in NTR1 positive/PSMA negative PC-3 tumors (1.4 ± 0.3%ID/g), but also in the PSMA positive/NTR1 negative LnCap tumors (1.3 ± 0.2% ID/g). The tracer showed comparable tumor to background ratio with each monomer. In summary, prostate cancer is a heterogeneous disease in need of improved diagnostics and treatments. The PSMA-NT heterodimer represents a new class of molecules that can be used to target two distinct antigens related to prostate cancer. In addition to the imaging applications demonstrated in this study, the agent also holds great potential on the treatment of heterogeneous prostate cancer.

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Prostate‐Specific Membrane Antigen (PSMA)‐Targeted Radionuclide Probes for Imaging and Therapy of Prostate Cancer

2019

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Prostate cancer (PCa) is one of the common cancers among men. Despite the prevalence of PCa, there are still unmet medical needs in the diagnosis and treatment of metastatic prostate cancer. Prostate‐specific membrane antigen (PSMA) is a type II zinc‐dependent metalloprotease which is highly overexpressed in metastatic PCa. In the last several years, PCa imaging probes targeting PSMA have been developed in academia as well as in industry. Among them, low molecular weight PSMA‐targeted ligands based on the Glu‐urea‐Lys scaffold have been evaluated in preclinical and clinical studies. This review provides an overview of the recent development in PSMA‐targeted imaging or therapeutic probes for metastatic PCa.

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The efficiency of ¹⁸F labelling of a prostate specific membrane antigen ligand via strain-promoted azide–alkyne reaction: reaction speed versus hydrophilicity

Cited by 9 publications

References 30 publications

Synthesis and Initial Biological Evaluation of Boron-Containing Prostate-Specific Membrane Antigen Ligands for Treatment of Prostate Cancer Using Boron Neutron Capture Therapy

Synthesis and Initial Biological Evaluation of Boron-Containing Prostate-Specific Membrane Antigen Ligands for Treatment of Prostate Cancer Using Boron Neutron Capture Therapy

Development of Bispecific NT-PSMA Heterodimer for Prostate Cancer Imaging: A Potential Approach to Address Tumor Heterogeneity

Prostate‐Specific Membrane Antigen (PSMA)‐Targeted Radionuclide Probes for Imaging and Therapy of Prostate Cancer

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