Rapid one-step 18F-radiolabeling of biomolecules in aqueous media by organophosphine fluoride acceptors

Hong, Huawei; Zhang, Lei; Xie, Fang; Zhuang, Rongqiang; Jiang, Donglang; Liu, Huanhuan; Li, Jindian; Yang, Hongzhang; Zhang, Xianzhong; Nie, Liming; Li, Zijing

doi:10.1038/s41467-019-08953-0

Cited by 36 publications

(41 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a completely noninvasive, fast imaging technique, it is also suitable for long-term monitoring. Our results demonstrate that PAI has the ability to monitor tumor volume changes and metastatic nodes, thus opening a new window for medical researchers to treat and diagnose patients without the danger of the ionizing radiation from CT or PET/CT (33). Alternatively, PAI might be used as a visualization tool for early stages of tumor formation in the liver.…”

Section: Discussionmentioning

confidence: 80%

Label-Free Visualization of Early Cancer Hepatic Micrometastasis and Intraoperative Image-Guided Surgery by Photoacoustic Imaging

Qian

Huang

et al. 2019

J Nucl Med

Self Cite

View full text Add to dashboard Cite

The detection of cancer micrometastasis for early diagnosis and treatment poses a great challenge for conventional imaging techniques. The aim of our study was to evaluate the performance of photoacoustic imaging (PAI) in detecting hepatic micrometastases from melanoma at a very early stage and in aiding tumor resection by intraoperative guidance. Methods: In vivo studies were performed by following protocols approved by the Ethical Committee for Animal Research at Xiamen University. First, a mouse model of B16 melanoma metastatic to the liver (n 5 10) was established to study the development of micrometastases in vivo. Next, the mice were imaged by a scalable PAI instrument, ultrasound, 9.4-T highresolution MRI, PET/CT, and bioluminescence imaging. PAI scans acquired with optical wavelengths of 680-850 nm were kept spectrally unmixed by using a linear least-squares method to differentiate various components. Differences in signal-to-background ratios among different modalities were determined with the 2-tailed paired t test. The diagnostic results were assessed with histologic examination. Excised liver samples from patients diagnosed with hepatic cancer were also examined to identify the tumor boundaries. Surgical removal of metastatic melanoma was precisely guided in vivo by the portable PAI system. Results: PAI was able to detect metastases as small as approximately 400 μm at a depth of up to 7 mm in vivo-a size that is smaller than can be detected with ultrasound and MRI. The tumor-to-liver ratio for PAI at 8 d (4.2 ± 0.2, n 5 6) and 14 d (9.2 ± 0.4, n 5 5) was significantly higher than for PET/CT (1.8 ± 0.1, n 5 5, and 4.5 ± 0.2, n 5 5, respectively; P , 0.001 for both). Functional PAI revealed dynamic oxygen saturation changes during tumor growth. The limit of detection was approximately 219 cells/μL in vitro. We successfully performed intraoperative PAI-guided surgery in vivo using the portable PAI system. Conclusion: Our findings offer a rapid and effective complementary clinical imaging application to noninvasively detect micrometastases and guide intraoperative resection.

show abstract

Section: Discussionmentioning

confidence: 80%

Label-Free Visualization of Early Cancer Hepatic Micrometastasis and Intraoperative Image-Guided Surgery by Photoacoustic Imaging

Qian

Huang

et al. 2019

J Nucl Med

Self Cite

View full text Add to dashboard Cite

show abstract

“…A futuristic view is to inject such a mixture, determine the boron concentration 3D map from the PET, qualify for therapy, plan the BNCT therapy, and execute it all within two h. PET image reconstruction needs a few minutes now, treatment planning needs much more time, but with the computer power increase and parallel and cloud computing, we may reach this level soon. NaBF 4 is a compound very specific for organs with natural NIS expression (thyroids, stomach, and pituitary gland), but the ease of labeling can be applied to any compound of the R-BF n type, which can sustain heating in a water solution to about 120 °C [ 21 ]. Such R-BF n -type compounds may be used in the future for BNCT theranostic treatments.…”

Section: Discussionmentioning

confidence: 99%

Quantification of Boron Compound Concentration for BNCT Using Positron Emission Tomography

Balcerzyk

Miguel

Guerrero

et al. 2020

Cells

View full text Add to dashboard Cite

Background: Boron neutron capture therapy requires a 2 mM 10B concentration in the tumor. The well-known BNCT patient treatment method using boronophenylalanine (BPA) as a boron-carrying agent utilizes [18F]fluoroBPA ([18F]FBPA) as an agent to qualify for treatment. Precisely, [18F]FBPA must have at least a 3:1 tumor to background tissue ratio to qualify the patient for BNCT treatment. Normal, hyperplasia, and cancer thyroids capture iodine and several other large ions, including BF4−, through a sodium-iodine symporter (NIS) expressed on the cell surface in normal conditions. In cancer, NIS is also expressed within the thyroid cell and is not functional. Methods: To visualize the thyroids and NIS, we have used a [18F]NaBF4 positron emission tomography (PET) tracer. It was injected into the tail veins of rats. The [18F]NaBF4 PET tracer was produced from NaBF4 by the isotopic exchange of natural 19F with radioactive 18F. Rats were subject to hyperplasia and tumor-inducing treatment. The NIS in thyroids was visualized by immunofluorescence staining. The boron concentration was calculated from Standard Uptake Values (SUV) in the PET/CT images and from the production data. Results: 41 MBq, 0.64 pmol of [18F]NaBF4 PET tracer that contained 0.351 mM, 53 nmol of NaBF4 was injected into the tail vein. After 17 min, the peak activity in the thyroid reached 2.3 MBq/mL (9 SUVmax). The natB concentration in the thyroid with hyperplasia reached 381 nM. Conclusions: Such an incorporation would require an additional 110 mg/kg dose of [10B]NaBF4 to reach the necessary 2 mM 10B concentration in the tumor. For future BNCT treatments of thyroid cancer, contrary to the 131I used now, there is no post-treatment radioactive decay, the patient can be immediately discharged from hospital, and there is no six-month moratorium for pregnancy. This method can be used for BNCT treatment compounds of the type R-BFn, where 1 <= n <= 3, labeled with 18F relatively easily, as in our example. A patient may undergo injection of a mixture of nonradioactive R-BFn to reach the necessary 10B concentration for BNCT treatment in the tumor together, with [18F]R-BFn for boron mapping.

show abstract

“…Recently, the radiolabeling of proteins through phosphorus fluorine bond formation was reported ( Hong et al, 2019 ). As with the other inorganic elements we have discussed, phosphorus readily forms bonds with fluorine.…”

Section: Strategies For Directly Radiolabeling Peptides and Proteins With Through Heteroatom-and Metal-[ 18 F]fluoridementioning

confidence: 99%

Reaction of [18F]Fluoride at Heteroatoms and Metals for Imaging of Peptides and Proteins by Positron Emission Tomography

2021

View full text Add to dashboard Cite

The ability to radiolabel proteins with [18F]fluoride enables the use of positron emission tomography (PET) for the early detection, staging and diagnosis of disease. The direct fluorination of native proteins through C-F bond formation is, however, a difficult task. The aqueous environments required by proteins severely hampers fluorination yields while the dry, organic solvents that promote nucleophilic fluorination can denature proteins. To circumvent these issues, indirect fluorination methods making use of prosthetic groups that are first fluorinated and then conjugated to a protein have become commonplace. But, when it comes to the radiofluorination of proteins, these indirect methods are not always suited to the short half-life of the fluorine-18 radionuclide (110 min). This review explores radiofluorination through bond formation with fluoride at boron, metal complexes, silicon, phosphorus and sulfur. The potential for these techniques to be used for the direct, aqueous radiolabeling of proteins with [18F]fluoride is discussed.

show abstract

Rapid one-step 18F-radiolabeling of biomolecules in aqueous media by organophosphine fluoride acceptors

Cited by 36 publications

References 49 publications

Label-Free Visualization of Early Cancer Hepatic Micrometastasis and Intraoperative Image-Guided Surgery by Photoacoustic Imaging

Label-Free Visualization of Early Cancer Hepatic Micrometastasis and Intraoperative Image-Guided Surgery by Photoacoustic Imaging

Quantification of Boron Compound Concentration for BNCT Using Positron Emission Tomography

Reaction of [18F]Fluoride at Heteroatoms and Metals for Imaging of Peptides and Proteins by Positron Emission Tomography

Contact Info

Product

Resources

About