scholarly journals Fluorine-18 Labeled Fluorofuranylnorprogesterone ([18F]FFNP) and Dihydrotestosterone ([18F]FDHT) Prepared by “Fluorination on Sep-Pak” Method

Molecules ◽  
2019 ◽  
Vol 24 (13) ◽  
pp. 2389 ◽  
Author(s):  
Falguni Basuli ◽  
Xiang Zhang ◽  
Burchelle Blackman ◽  
Margaret E. White ◽  
Elaine M. Jagoda ◽  
...  
Keyword(s):  
Androgen Receptors ◽  
Quantitative Measure ◽  
Emission Tomography ◽  
In Vitro Assays ◽  
Affinity Binding ◽  
Synthesis Time ◽  
High Affinity ◽  
Molar Activity ◽  
Positron Emission

To further explore the scope of our recently developed “fluorination on Sep-Pak” method, we prepared two well-known positron emission tomography (PET) tracers 21-[18F]fluoro-16α,17α-[(R)-(1′-α-furylmethylidene)dioxy]-19-norpregn-4-ene-3,20-dione furanyl norprogesterone ([18F]FFNP) and 16β-[18F]fluoro-5α-dihydrotestosterone ([18F]FDHT). Following the “fluorination on Sep-Pak” method, over 70% elution efficiency was observed with 3 mg of triflate precursor of [18F]FFNP. The overall yield of [18F]FFNP was 64–72% (decay corrected) in 40 min synthesis time with a molar activity of 37–81 GBq/µmol (1000–2200 Ci/mmol). Slightly lower elution efficiency (~55%) was observed with the triflate precursor of [18F]FDHT. Fluorine-18 labeling, reduction, and deprotection to prepare [18F]FDHT were performed on Sep-Pak cartridges (PS-HCO3 and Sep-Pak plus C-18). The overall yield of [18F]FDHT was 25–32% (decay corrected) in 70 min. The molar activity determined by using mass spectrometry was 63–148 GBq/µmol (1700–4000 Ci/mmol). Applying this quantitative measure of molar activity to in vitro assays [18F]FDHT exhibited high-affinity binding to androgen receptors (Kd~2.5 nM) providing biological validation of this method.

scholarly journals 3D-printed automation for optimized PET radiochemistry

2019 ◽  
Vol 5 (9) ◽  
pp. eaax4762
Author(s):  
Alejandro Amor-Coarasa ◽  
James M. Kelly ◽  
John W. Babich
Keyword(s):  
Three Dimensional ◽  
Emission Tomography ◽  
Reaction Conditions ◽  
Synthesis Time ◽  
Reduce Radiation Exposure ◽  
Molar Activity ◽  
Positron Emission ◽  
3D Printed ◽  
Fit For Purpose ◽  
The Cost

Reproducible batch synthesis of radioligands for imaging by positron emission tomography (PET) in a manner that maximizes ligand yield, purity, and molar activity, and minimizes cost and exposure to radiation, remains a challenge, as new and synthetically complex radioligands become available. Commercially available automated synthesis units (ASUs) solve many of these challenges but are costly to install and cannot always accommodate diverse chemistries. Through a reiterative design process, we exploit the proliferation of three-dimensional (3D) printing technologies to translate optimized reaction conditions into ASUs composed of 3D-printed, electronic, and robotic parts. Our units are portable and robust and reduce radiation exposure, shorten synthesis time, and improve the yield of the final radiopharmaceutical for a fraction of the cost of a commercial ASU. These 3D-printed ASUs highlight the gains that can be made by designing a fit-for-purpose ASU to accommodate a synthesis over accommodating a synthesis to an unfit ASU.

scholarly journals Evaluation of 2-[18F]-Fluorodeoxysorbitol PET Imaging in Preclinical Models of Aspergillus Infection

2021 ◽  
Vol 8 (1) ◽  
pp. 25
Author(s):  
Jianhao Lai ◽  
Swati Shah ◽  
Rekeya Knight ◽  
Neysha Martinez-Orengo ◽  
Reema Patel ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Fungal Infections ◽  
Emission Tomography ◽  
In Vitro Assays ◽  
Preclinical Models ◽  
Mortality And Morbidity ◽  
E Coli ◽  
Positron Emission ◽  
Infection Models

Despite increasing associated mortality and morbidity, the diagnosis of fungal infections, especially with Aspergillus fumigatus (A. fumigatus), remains challenging. Based on known ability of Aspergillus species to utilize sorbitol, we evaluated 2-[18F]-fluorodeoxysorbitol (FDS), a recently described Enterobacterales imaging ligand, in animal models of A. fumigatus infection, in comparison with 2-[18F]-fluorodeoxyglucose (FDG). In vitro assays showed slightly higher 3H-sorbitol uptake by live compared with heat-killed A. fumigatus. However, this was 10.6-fold lower than E. coli uptake. FDS positron emission tomography (PET) imaging of A. fumigatus pneumonia showed low uptake in infected lungs compared with FDG (0.290 ± 0.030 vs. 8.416 ± 0.964 %ID/mL). This uptake was higher than controls (0.098 ± 0.008 %ID/mL) and minimally higher than lung inflammation (0.167 ± 0.007 %ID/mL). In the myositis models, FDS uptake was highest in live E. coli infections. Uptake was low in A. fumigatus myositis model and only slightly higher in live compared with the heat-killed side. In conclusion, we found low uptake of 3H-sorbitol and FDS by A. fumigatus cultures and infection models compared with E. coli, likely due to the need for induction of sorbitol dehydrogenase by sorbitol. Our findings do not support FDS as an Aspergillus imaging agent. At this point, FDS remains more selective for imaging Gram-negative Enterobacterales.

scholarly journals Development of a blood sample detector for multi-tracer positron emission tomography using gamma spectroscopy

2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Carlos Velasco ◽  
Adriana Mota-Cobián ◽  
Jesús Mateo ◽  
Samuel España
Keyword(s):  
Positron Emission Tomography ◽  
Blood Sample ◽  
Pet Imaging ◽  
Spectroscopic Analysis ◽  
Gamma Spectroscopy ◽  
Emission Tomography ◽  
Blood Samples ◽  
Positron Emission

Abstract Background Multi-tracer positron emission tomography (PET) imaging can be accomplished by applying multi-tracer compartment modeling. Recently, a method has been proposed in which the arterial input functions (AIFs) of the multi-tracer PET scan are explicitly derived. For that purpose, a gamma spectroscopic analysis is performed on blood samples manually withdrawn from the patient when at least one of the co-injected tracers is based on a non-pure positron emitter. Alternatively, these blood samples required for the spectroscopic analysis may be obtained and analyzed on site by an automated detection device, thus minimizing analysis time and radiation exposure of the operating personnel. In this work, a new automated blood sample detector based on silicon photomultipliers (SiPMs) for single- and multi-tracer PET imaging is presented, characterized, and tested in vitro and in vivo. Results The detector presented in this work stores and analyzes on-the-fly single and coincidence detected events. A sensitivity of 22.6 cps/(kBq/mL) and 1.7 cps/(kBq/mL) was obtained for single and coincidence events respectively. An energy resolution of 35% full-width-half-maximum (FWHM) at 511 keV and a minimum detectable activity of 0.30 ± 0.08 kBq/mL in single mode were obtained. The in vivo AIFs obtained with the detector show an excellent Pearson’s correlation (r = 0.996, p < 0.0001) with the ones obtained from well counter analysis of discrete blood samples. Moreover, in vitro experiments demonstrate the capability of the detector to apply the gamma spectroscopic analysis on a mixture of 68Ga and 18F and separate the individual signal emitted from each one. Conclusions Characterization and in vivo evaluation under realistic experimental conditions showed that the detector proposed in this work offers excellent sensibility and stability. The device also showed to successfully separate individual signals emitted from a mixture of radioisotopes. Therefore, the blood sample detector presented in this study allows fully automatic AIFs measurements during single- and multi-tracer PET studies.

scholarly journals PET Imaging of GPR44 by Antagonist [11C]MK-7246 in Pigs

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 434
Author(s):  
Pierre Cheung ◽  
Bo Zhang ◽  
Emmi Puuvuori ◽  
Sergio Estrada ◽  
Mohammad A. Amin ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Emission Tomography ◽  
Pet Tracer ◽  
Positron Emission ◽  
In Vitro Cell Lines ◽  
Membrane Spanning ◽  
New Strategies

A validated imaging marker for beta-cell mass would improve understanding of diabetes etiology and enable new strategies in therapy development. We previously identified the membrane-spanning protein GPR44 as highly expressed and specific to the beta cells of the pancreas. The selective GPR44 antagonist MK-7246 was radiolabeled with carbon-11 and the resulting positron-emission tomography (PET) tracer [11C]MK-7246 was evaluated in a pig model and in vitro cell lines. The [11C]MK-7246 compound demonstrated mainly hepatobiliary excretion with a clearly defined pancreas, no spillover from adjacent tissues, and pancreatic binding similar in magnitude to the previously evaluated GPR44 radioligand [11C]AZ12204657. The binding could be blocked by preadministration of nonradioactive MK-7246, indicating a receptor-binding mechanism. [11C]MK-7246 showed strong potential as a PET ligand candidate for visualization of beta-cell mass (BCM) and clinical translation of this methodology is ongoing.

Shark Attack: High affinity binding proteins derived from shark vNAR domains by stepwise in vitro affinity maturation

2014 ◽  
Vol 191 ◽  
pp. 236-245 ◽  
Author(s):  
Stefan Zielonka ◽  
Niklas Weber ◽  
Stefan Becker ◽  
Achim Doerner ◽  
Andreas Christmann ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Affinity Maturation ◽  
Affinity Binding ◽  
High Affinity Binding ◽  
High Affinity

scholarly journals Anatomic and Biochemical Correlates of the Dopamine Transporter Ligand 11C-PE2I in Normal and Parkinsonian Primates: Comparison with 6-[18F]Fluoro-L-Dopa

2001 ◽  
Vol 21 (7) ◽  
pp. 782-792 ◽  
Author(s):  
Thomas Poyot ◽  
Françoise Condé ◽  
Marie-Claude Grégoire ◽  
Vincent Frouin ◽  
Christine Coulon ◽  
...  
Keyword(s):  
Gold Standard ◽  
Dopaminergic Neurons ◽  
Emission Tomography ◽  
Attractive Alternative ◽  
Input Rate ◽  
Nigrostriatal Pathway ◽  
Positron Emission ◽  
Neuroprotective Strategies

Positron emission tomography (PET) coupled to 6-[18F]Fluoro-L-Dopa (18F-Dopa) remains the gold standard for assessing dysfunctionality concerning the dopaminergic nigrostriatal pathway in Parkinson's disease and related disorders. The use of ligands of the dopamine transporters (DAT) is an attractive alternative target; consequently, the current aim was to validate one of them, 11C-PE2I, using a multiinjection modeling approach allowing accurate quantitation of DAT densities in the striatum. Experiments were performed in three controls, three MPTP-treated (parkinsonian) baboons, and one reserpine-treated baboon. 11C-PE2I B′max values obtained with this approach were compared with 18F-Dopa input rate constant values (Ki), in vitro Bmax binding of 125I-PE2I, and the number of dopaminergic neurons in the substantia nigra estimated postmortem by stereology. In the caudate nucleus and putamen, control values for 11C-PE2I B'max were 673 and 658 pmol/mL, respectively, whereas it was strongly reduced in the MPTP-treated (B′max = 26 and 36 pmol/mL) and reserpine-treated animals (B′max = 338 and 483 pmol/mL). In vivo11C-PE2I B′max values correlated with 18F-Dopa Ki values and in vitro125I-PE2I Bmax values in the striatum and with the number of nigral dopaminergic neurons. Altogether, these data support the use of 11C-PE2I for monitoring striatal dopaminergic disorders and the effect of potential neuroprotective strategies.

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