scholarly journals Development of Radiofluorinated Nicotinamide/Picolinamide Derivatives as Diagnostic Probes for the Detection of Melanoma

2021 ◽  
Vol 22 (12) ◽  
pp. 6432
Author(s):  
Yi-Hsuan Lo ◽  
Ting-Yu Chang ◽  
Chuan-Lin Chen ◽  
Ming-Hsien Lin ◽  
Hsin-Ell Wang ◽  
...  
Keyword(s):  
Experimental Period ◽  
Detection Methods ◽  
Log P ◽  
Tumor Bearing ◽  
B16f10 Cells ◽  
Biodistribution Studies ◽  
Positron Emission ◽  
B16f10 Tumor ◽  
Radiochemical Yields ◽  
A375 Cells

Regarding the increased incidence and high mortality rate of malignant melanoma, practical early-detection methods are essential to improve patients’ clinical outcomes. In this study, we successfully prepared novel picolinamide–benzamide (18F-FPABZA) and nicotinamide–benzamide (18F-FNABZA) conjugates and determined their biological characteristics. The radiochemical yields of 18F-FPABZA and 18F-FNABZA were 26 ± 5% and 1 ± 0.5%, respectively. 18F-FPABZA was more lipophilic (log P = 1.48) than 18F-FNABZA (log P = 0.68). The cellular uptake of 18F-FPABZA in melanotic B16F10 cells was relatively higher than that of 18F-FNABZA at 15 min post-incubation. However, both radiotracers did not retain in amelanotic A375 cells. The tumor-to-muscle ratios of 18F-FPABZA-injected B16F10 tumor-bearing mice increased from 7.6 ± 0.4 at 15 min post-injection (p.i.) to 27.5 ± 16.6 at 3 h p.i., while those administered with 18F-FNABZA did not show a similarly dramatic increase throughout the experimental period. The results obtained from biodistribution studies were consistent with those derived from microPET imaging. This study demonstrated that 18F-FPABZA is a promising melanin-targeting positron emission tomography (PET) probe for melanotic melanoma.

scholarly journals Simplified 89Zr-Labeling Protocol of Oxine (8-Hydroxyquinoline) Enabling Prolonged Tracking of Liposome-Based Nanomedicines and Cells

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1097
Author(s):  
Andras Polyak ◽  
Jens P. Bankstahl ◽  
Karen F. W. Besecke ◽  
Constantin Hozsa ◽  
Wiebke Triebert ◽  
...  
Keyword(s):  
Reaction Times ◽  
Extraction Methods ◽  
Cell Labeling ◽  
Size Exclusion ◽  
Cell Therapies ◽  
Biodistribution Studies ◽  
Positron Emission ◽  
Human Ipscs ◽  
Radiochemical Yields

In this work, a method for the preparation of the highly lipophilic labeling synthon [89Zr]Zr(oxinate)4 was optimized for the radiolabeling of liposomes and human induced pluripotent stem cells (hiPSCs). The aim was to establish a robust and reliable labeling protocol for enabling up to one week positron emission tomography (PET) tracing of lipid-based nanomedicines and transplanted or injected cells, respectively. [89Zr]Zr(oxinate)4 was prepared from oxine (8-hydroxyquinoline) and [89Zr]Zr(OH)2(C2O4). Earlier introduced liquid–liquid extraction methods were simplified by the optimization of buffering, pH, temperature and reaction times. For quality control, thin-layer chromatography (TLC), size-exclusion chromatography (SEC) and centrifugation were employed. Subsequently, the 89Zr-complex was incorporated into liposome formulations. PET/CT imaging of 89Zr-labeled liposomes was performed in healthy mice. Cell labeling was accomplished in PBS using suspensions of 3 × 106 hiPSCs, each. [89Zr]Zr(oxinate)4 was synthesized in very high radiochemical yields of 98.7% (96.8% ± 2.8%). Similarly, high internalization rates (≥90%) of [89Zr]Zr(oxinate)4 into liposomes were obtained over an 18 h incubation period. MicroPET and biodistribution studies confirmed the labeled nanocarriers’ in vivo stability. Human iPSCs incorporated the labeling agent within 30 min with ~50% efficiency. Prolonged PET imaging is an ideal tool in the development of lipid-based nanocarriers for drug delivery and cell therapies. To this end, a reliable and reproducible 89Zr radiolabeling method was developed and tested successfully in a model liposome system and in hiPSCs alike.

scholarly journals Microwave-assisted radiolabelling of 52Mn-porphyrins

2021 ◽  
Author(s):  
Peter J. Gawne ◽  
Sara M. A. Pinto ◽  
Karin M. Nielsen ◽  
Mariette M. Pereira ◽  
Rafael T. M. de Rosales
Keyword(s):  
Lipid Bilayers ◽  
Mri Contrast Agents ◽  
Mri Contrast ◽  
Manganese Porphyrins ◽  
Biodistribution Studies ◽  
Positron Emission ◽  
Radiochemical Yields

Manganese porphyrins have several therapeutic/imaging applications; including their use as radioprotectants (in clinical trials), and as paramagnetic MRI contrast agents. The affinity of porphyrins for lipid bilayers also makes them candidates for cell/liposome labelling. We hypothesised that metalation with the positron emission tomography (PET) radionuclide 52Mn (t1/2 = 5.6 d) would allow long-term in vivo biodistribution studies of Mn-porphyrins as well as a method to label and track cells/liposomes, but methods for fast and efficient radiolabelling are lacking. Several porphyrins were produced and radiolabelled by addition to neutralised [52Mn]MnCl2 and heated at 165 oC for 1 h using a microwave (MW) synthesiser at a ligand concentration of 0.6 – 0.7 mM. These conditions were compared with non-MW heating at 70oC. MW radiosynthesis allowed >95 % radiochemical yields (RCY) in just 1 h. Conversely, non-MW heating at 70 oC for 1 h resulted in low RCY (0 – 25 % RCY) and most porphyrins did not reach completion after 24h. Formation of the 52Mn-complexes were confirmed with radio-HPLC by comparison with their non-radioactive 55Mn counterparts. Following this, several 52Mn-porphyrins were used to radiolabel liposomes by incubation at 50 oC for 30 min resulting in 75 – 86 % labelling efficiency (LE). Two lead 52Mn-porphyrins were taken forward to label MDA-MB-231 cancer cells in vitro, achieving ca. 11 % LE. After 24 h, 32 – 45 % of the 52Mn-porphyrin was retained in cells. In contrast to standard methods, MW heating allows fast synthesis of 52Mn-porphyrins with >95% radiochemical yields that avoid purification. 52Mn-porphyrins also show promising cell/liposome labelling properties. This technique can potentially be exploited for the in vivo imaging of Mn-porphyrin therapeutics, as well as for the accurate in vivo quantification of Mn-porphyrin MRI agents.

Copper-64 labeled sulfophthalocyanines for positron emission tomography (PET) imaging in tumor-bearing rats

2008 ◽  
Vol 12 (01) ◽  
pp. 49-53 ◽  
Author(s):  
Anton Soucy-Faulkner ◽  
Jacques A. Rousseau ◽  
Réjean Langlois ◽  
Véronique Berard ◽  
Roger Lecomte ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Photodynamic Therapy ◽  
Emission Tomography ◽  
Tumor Uptake ◽  
Tissue Samples ◽  
Metal Free ◽  
Tumor Bearing ◽  
Biodistribution Studies ◽  
Positron Emission ◽  
Tumor Selectivity

Sulfonated metallophthalocyanines ( PcS ) are second generation photosensitizers for photodynamic therapy (PDT) of cancer. Metal-free H 2 PcS are readily labeled with 64 Cu ++ to yield a mixture of sulfonated [64 Cu ] CuPcS suitable for biodistribution studies in tumor-bearing rats by positron emission tomography (PET). Most of the 64 Cu activity was sequestrated within the kidneys (20%ID/g) and liver (12%ID/g) while tumor uptake values remained low (0.2%ID/g). Dissection and counting of individual tissue samples after the 24 h scan confirmed the uptake values derived from the PET images. The procedure can be applied to series of novel PcS to evaluate structure-tumor selectivity relationships as a parameter to select potential agents for photodynamic therapy.

scholarly journals Effect of ethanol and cocaine on [11C]MPC-6827 uptake in SH-SY5Y cells

2021 ◽  
Author(s):  
Naresh Damuka ◽  
Miranda Orr ◽  
Paul W. Czoty ◽  
Jeffrey L. Weiner ◽  
Thomas J. Martin ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Ex Vivo ◽  
Neuroblastoma Cells ◽  
Proper Function ◽  
Brain Functions ◽  
Biodistribution Studies ◽  
Positron Emission ◽  
Vitro Binding

AbstractMicrotubules (MTs) are structural units in the cytoskeleton. In brain cells they are responsible for axonal transport, information processing, and signaling mechanisms. Proper function of these processes is critical for healthy brain functions. Alcohol and substance use disorders (AUD/SUDs) affects the function and organization of MTs in the brain, making them a potential neuroimaging marker to study the resulting impairment of overall neurobehavioral and cognitive processes. Our lab reported the first brain-penetrant MT-tracking Positron Emission Tomography (PET) ligand [11C]MPC-6827 and demonstrated its in vivo utility in rodents and non-human primates. To further explore the in vivo imaging potential of [11C]MPC-6827, we need to investigate its mechanism of action. Here, we report preliminary in vitro binding results in SH-SY5Y neuroblastoma cells exposed to ethanol (EtOH) or cocaine in combination with multiple agents that alter MT stability. EtOH and cocaine treatments increased MT stability and decreased free tubulin monomers. Our initial cell-binding assay demonstrated that [11C]MPC-6827 may have high affinity to free/unbound tubulin units. Consistent with this mechanism of action, we observed lower [11C]MPC-6827 uptake in SH-SY5Y cells after EtOH and cocaine treatments (e.g., fewer free tubulin units). We are currently performing in vivo PET imaging and ex vivo biodistribution studies in rodent and nonhuman primate models of AUD and SUDs and Alzheimer's disease.

scholarly journals Optimised GMP-compliant production of [18F]DPA-714 on the Trasis AllinOne module

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Klaudia A. Cybulska ◽  
Vera Bloemers ◽  
Lars R. Perk ◽  
Peter Laverman
Keyword(s):  
Significant Degree ◽  
Translocator Protein ◽  
Positron Emission ◽  
Leaving Group ◽  
Inflammatory Processes ◽  
Single Production ◽  
Translocator Protein 18 Kda ◽  
Radiochemical Yields ◽  
Specific Ligand

Abstract Background The translocator protein 18 kDa is recognised as an important biomarker for neuroinflammation due to its soaring expression in microglia. This process is common for various neurological disorders. DPA-714 is a potent TSPO-specific ligand which found its use in Positron Emission Tomography following substitution of fluorine-19 with fluorine-18, a positron-emitting radionuclide. [18F]DPA-714 enables visualisation of inflammatory processes in vivo non-invasively. Radiolabelling of this tracer is well described in literature, including validation for clinical use. Here, we report significant enhancements to the process which resulted in the design of a fully GMP-compliant robust synthesis of [18F]DPA-714 on a popular cassette-based system, Trasis AllinOne, boosting reliability, throughput, and introducing a significant degree of simplicity. Results [18F]DPA-714 was synthesised using the classic nucleophilic aliphatic substitution on a good leaving group, tosylate, with [18F]fluoride using tetraethylammonium bicarbonate in acetonitrile at 100∘C. The process was fully automated on a Trasis AllinOne synthesiser using an in-house designed cassette and sequence. With a relatively small precursor load of 4 mg, [18F]DPA-714 was obtained with consistently high radiochemical yields of 55-71% (n=6) and molar activities of 117-350 GBq/µmol at end of synthesis. With a single production batch, starting with 31-42 GBq of [18F]fluoride, between 13-20 GBq of the tracer can be produced, enabling multi-centre studies. Conclusion To the best of our knowledge, the process presented herein is the most efficient [18F]DPA-714 synthesis, with advantageous GMP compliance. The use of a Trasis AllinOne synthesiser increases reliability and allows rapid training of production staff.

scholarly journals Harnessing PET to track micro- and nanoplastics in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Outi Keinänen ◽  
Eric J. Dayts ◽  
Cindy Rodriguez ◽  
Samantha M. Sarrett ◽  
James M. Brennan ◽  
...  
Keyword(s):  
Sea Water ◽  
Accurate Determination ◽  
Nuclear Imaging ◽  
Imaging Data ◽  
Biodistribution Studies ◽  
Positron Emission ◽  
20 Nm ◽  
Pharmacokinetic Behavior

AbstractThe proliferation of plastics in the environment continues at an alarming rate. Plastic particles have been found to be persistent and ubiquitous pollutants in a variety of environments, including sea water, fresh water, soil, and air. In light of this phenomenon, the scientific and medical communities have become increasingly wary of the dangers posed to human health by chronic exposure to microplastics (< 5 mm diameter) and nanoplastics (< 100 nm diameter). A critical component of the study of the health effects of these pollutants is the accurate determination of their pharmacokinetic behavior in vivo. Herein, we report the first use of molecular imaging to track polystyrene (PS) micro- and nanoplastic particles in mammals. To this end, we have modified PS particles of several sizes—diameters of 20 nm, 220 nm, 1 µm, and 6 µm—with the chelator desferrioxamine (DFO) and radiolabeled these DFO-bearing particles with the positron-emitting radiometal zirconium-89 (89Zr; t1/2 ~ 3.3 d). Subsequently, positron emission tomography (PET) was used to visualize the biodistribution of these radioplastics in C57BL/6J mice at 6, 12, 24, and 48 h after ingestion. The imaging data reveal that the majority of the radioplastics remain in the gastrointestinal tract and are eliminated through the feces by 48 h post-ingestion, a result reinforced by acute biodistribution studies. Ultimately, this work suggests that nuclear imaging—and PET in particular—can be a sensitive and effective tool in the urgent and rapidly growing effort to study the in vivo behavior and potential toxicity of micro- and nanoplastics.

scholarly journals New 55Co-labeled Albumin-Binding Folate Derivatives as Potential PET Agents for Folate Receptor Imaging

2019 ◽  
Vol 12 (4) ◽  
pp. 166 ◽  
Author(s):  
Lauren L. Radford ◽  
Solana Fernandez ◽  
Rebecca Beacham ◽  
Retta El Sayed ◽  
Renata Farkas ◽  
...  
Keyword(s):  
Folate Receptor ◽  
Small Animal ◽  
Small Animal Pet ◽  
Receptor Imaging ◽  
Albumin Binding ◽  
Liver Uptake ◽  
Biodistribution Studies ◽  
Positron Emission

Overexpression of folate receptors (FRs) on different tumor types (e.g., ovarian, lung) make FRs attractive in vivo targets for directed diagnostic/therapeutic agents. Currently, no diagnostic agent suitable for positron emission tomography (PET) has been adopted for clinical FR imaging. In this work, two 55Co-labeled albumin-binding folate derivatives-[55Co]Co-cm10 and [55Co]Co-rf42-with characteristics suitable for PET imaging have been developed and evaluated. High radiochemical yields (≥95%) and in vitro stabilities (≥93%) were achieved for both compounds, and cell assays demonstrated FR-mediated uptake. Both 55Co-labeled folate conjugates demonstrated high tumor uptake of 17% injected activity per gram of tissue (IA/g) at 4 h in biodistribution studies performed in KB tumor-bearing mice. Renal uptake was similar to other albumin-binding folate derivatives, and liver uptake was lower than that of previously reported [64Cu]Cu-rf42. Small animal PET/CT images confirmed the biodistribution results and showed the clear delineation of FR-expressing tumors.

scholarly journals Positron Emission Tomography (PET) and Pharmacokinetics: Classical Blood Sampling Versus Image-Derived Analysis of [18F]FAZA and [18F]FDG in a Murine Tumor Bearing Model

2018 ◽  
Vol 21 (1s) ◽  
pp. 32s-47s ◽  
Author(s):  
Hans-Soenke Jans ◽  
Xiao-Hong Yang ◽  
Dion R Brocks ◽  
Piyush Kumar ◽  
Melinda Wuest ◽  
...  
Keyword(s):  
Inferior Vena ◽  
Vena Cava ◽  
Blood Sampling ◽  
Tumor Uptake ◽  
Blood Samples ◽  
Non Invasive ◽  
Tumor Bearing ◽  
Positron Emission ◽  
18F Fdg ◽  
Derived Data

Purpose: Pharmacokinetic (PK) data are generally derived from blood samples withdrawn serially over a defined period after dosing. In small animals, blood sampling after dosing presents technical difficulties, particularly when short time intervals and frequent sampling are required. Positron emission tomography (PET) is a non-invasive functional imaging technique that can provide semi-quantitative temporal data for defined volume regions of interest (vROI), to support kinetic analyses in blood and other tissues. The application of preclinical small-animal PET to determine and compare PK parameters for [18F]FDG and [18F]FAZA, radiopharmaceuticals used clinically for assessing glucose metabolism and hypoxic fractions, respectively, in the same mammary EMT6 tumor-bearing mouse model, is reported here. Methods: Two study groups were used: normal BALB/c mice under isoflurane anesthesia were intravenously injected with either [18F]FDG or [18F]FAZA. For the first group, blood-sampling by tail artery puncture was used to collect blood samples which were then analyzed with Radio-microTLC. Dynamic PET experiments were performed with the second group of mice and analyzed for blood input function and tumor uptake utilizing a modified two compartment kinetic model. Heart and inferior vena cava vROIs were sampled to obtain image-derived data. PK parameters were calculated from blood samples and image-derived data. Time-activity curves (TACs) were also generated over regions of liver, kidney and urinary bladder to depict clearance profiles for each radiotracer. Results: PK values generated by classical blood sampling and PET image-derived analysis were comparable to each other for both radiotracers. Heart vROI data were suitable for analysis of [18F]FAZA kinetics, but metabolic uptake of radioactivity mandated the use of inferior vena cava vROIs for [18F]FDG analysis. While clearance (CL) and blood half-life (t½) were similar for both [18F]FDG and [18F]FAZA for both sampling methods, volume of distribution yielded larger differences, indicative of limitations such as partial volume effects within quantitative image-derived data. [18F]FDG underwent faster blood clearance and had a shorter blood half-life than [18F]FAZA. Kinetic analysis of tumor uptake from PET image data showed higher uptake and longer tumor tissue retention of [18F]FDG, indicative of the tumor’s glucose metabolism rate, versus lower tumor uptake and retention of [18F]FAZA. While [18F]FAZA possesses a somewhat greater hepatobiliary clearance , [18F]FDG clears faster through the renal system which results in faster radioactivity accumulation in the urinary bladder. Conclusions: The present study provides a working example of the applicability of functional PET imaging as a suitable tool to determine PK parameters in small animals. The comparative analysis in the current study demonstrates that it is feasible to use [18F]FDG PET and [18F]FAZA PET in the same model to analyze their blood PK parameters, and to estimate kinetic parameters for these tracers in tumor. This non-invasive imaging-based determination of tissue kinetic parameters facilitates translation from pre-clinical to clinical phases of drug development. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Synthesis of a new 18F labeled porphyrin for potential application in positron emission tomography. In vivo imaging and cellular uptake

RSC Advances ◽  
2015 ◽  
Vol 5 (120) ◽  
pp. 99540-99546 ◽  
Author(s):  
Ana V. C. Simões ◽  
Sara M. A. Pinto ◽  
Mário J. F. Calvete ◽  
Célia M. F. Gomes ◽  
Nuno C. Ferreira ◽  
...  
Keyword(s):  
In Vivo Imaging ◽  
Bladder Tumor ◽  
Radiochemical Purity ◽  
Cell Uptake ◽  
Emission Tomography ◽  
Human Bladder ◽  
Biodistribution Studies ◽  
Biodistribution Data ◽  
Positron Emission

Synthesis, labeling and initial biodistribution studies of a new [18F] radiolabeled meso-tetraphenylporphyrin (radiochemical purity >95%). Includes human bladder tumor cell uptake and biodistribution data.

Sign in / Sign up

Export Citation Format

Share Document