scholarly journals Repurposing 18F-FMISO as a PET tracer for translational imaging of nitroreductase-based gene directed enzyme prodrug therapy

Theranostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 6044-6057
Author(s):  
Gorka Ruiz de Garibay ◽  
Elvira García de Jalón ◽  
Endre Stigen ◽  
Kjetil B Lund ◽  
Mihaela Popa ◽  
...  
Keyword(s):  
Enzyme Prodrug Therapy ◽  
Pet Tracer ◽  
Translational Imaging

Comparison of diagnostic accuracy of 18F-FDG PET, 123I-IMT- and 99mTc-MIBI SPECT

2006 ◽  
Vol 45 (01) ◽  
pp. 49-56 ◽  
Author(s):  
N. Özdemir-Sahin ◽  
P. Hipp ◽  
W. Mier ◽  
M. Eisenhut ◽  
J. Debus ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Fdg Pet ◽  
Tumour Progression ◽  
Roc Curves ◽  
Low Grade ◽  
Who Grade ◽  
Pet Tracer ◽  
Patient Groups ◽  
99Mtc Mibi ◽  
Mibi Spect

Summary Aim was to evaluates the diagnostic accuracy of the SPECTtracers 3-123I-α-methyl-L-tyrosine (IMT) and 99mTc(I)- hexakis(2-methoxyisobutylisonitrile) (MIBI) as well as the PET-tracer 2-18F-2-deoxyglucose (FDG) for detecting tumour progression in irradiated low grade astrocytomas (LGA). Patients, methods: We examined 91 patients (56 males; 35 females; 44.7 ± 11.5 years), initially suffering from histologically proven LGAs (mean WHO grade II) and treated by stereotactic radiotherapy (59.0 ± 4.6 Gy). On average 21.9 ± 11.2 months after radiotherapy, patients presented new Gd-DTPA enhancing lesions on MRI, which did not allow a differentiation between progressive tumour (PT) and non-PT (nPT) at this point of time. PET scans (n=82) were acquired 45 min after injection of 208 ± 32 MBq FDG. SPECT scans started 10 min after injection of 269 ± 73 MBq IMT (n=68) and 15 min after injection of 706 ± 63 MBq MIBI (n=34). Lesions were classified as PT and nPT based on prospective follow-up (clinically, MRI) for 17.2 ± 9.9 months after PET/SPECT. Lesion-to-normal ratios (L/N) were calculated using contra lateraly mirrored reference regions for the SPECT examinations and reference regions in the contra lateral grey (GM) and white matter (WM) for FDG PET. Ratios were evaluated by Receiver Operating Characteristic (ROC) analysis. Results: In the patient groups nPT and PT, L/N ratios for FDG (GS) were 0.6 ± 0.3 vs. 1.2 ± 0.5 (p = 0.003), for FDG (WS) 1.2 ± 0.4 vs. 2.6 ± 0.4 (p <0.001), for IMT 1.1 ± 0.1 vs. 1.8 ± 0.4 (p <0.001) and for MIBI 1.6 ± 0.7 vs. 2.6 ± 2.2 (p = 0.554). Areas under the non-parametric ROC-curves were: 0.738 ± 0.059 for FDG (GS), 0.790 ± 0.057 for FDG (WS), 0.937 ± 0.037 for IMT and 0.564 ± 0.105 for MIBI. Conclusion: MIBI-SPECT examinations resulted in a low accuracy and especially in a poor sensitivity even at modest specificity values. A satisfying diagnostic accuracy was reached with FDG PET. Using WM as reference region for FDG PET, a slightly higher AUC as compared to GM was calculated. IMT yielded the best ROC characteristics and the highest diagnostic accuracy for differentiating between PT and nPT in irradiated LGA.

Klinischer Nutzen nuklearmedizinischer Verfahren in der Demenzdiagnostik

2009 ◽  
Vol 28 (10) ◽  
pp. 709-717
Author(s):  
A. Drzezga
Keyword(s):  
Post Mortem ◽  
Klinischer Nutzen ◽  
Pet Tracer

ZusammenfassungEine sichere Diagnose neurodegenerativer Demenzerkrankungen kann nur mittels post mortem histopathologischer Evaluation des Gehirngewebes erfolgen. Es ist akzeptiert, dass die pathologischen Veränderungen Jahre bis Jahrzehnte vor Beginn der klinischen Symptomatik einsetzen. Der Nutzen klinischneuropsychologischer Maße für die frühe Diagnostik dieser Erkrankungen im vor- oder geringsymptomatischen Stadium ist somit limitiert. Die zum Teil deutliche symptomatische Überlappung unterschiedlicher Demenzerkrankungen erschwert zusätzlich die klinische Differenzialdiagnostik. Insbesondere neue Therapieansätze machen aber eine frühe und zuverlässige Differenzialdiagnose immer wichtiger, was den Bedarf an geeigneten Biomarkern unterstreicht. Hier sollen zwei Verfahren der molekularen und funktionellen Bildgebung behandelt werden, die vielversprechend und gut evaluiert sind: Die FDGPET (Positronen Emissions Tomografie) als Marker der regionalen neuronalen Dysfunktion. Und die Amyloidplaquebildgebung mittels moderner PET-Tracer wie dem PIB. Deren Wertigkeit in der Früh- und Differenzialdiagnostik sowie für die Patientenselektion für Therapiestudien und für eine objektive Therapiekontrolle wird diskutiert.

Comparison of 18F-FDG and 67Ga-citrate in sarcoidosis imaging

2008 ◽  
Vol 47 (01) ◽  
pp. 18-23 ◽  
Author(s):  
M. Wehrschuetz ◽  
B. Bisail ◽  
M. Woltsche ◽  
T. Schwarz ◽  
H. Lanz ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Complete Agreement ◽  
Pet Tracer ◽  
Positron Emission ◽  
Significant Difference ◽  
Kappa Value ◽  
18F Fdg ◽  
Primary Assessment ◽  
67Ga Citrate

SummaryAim: 67Ga citrate has been used long and successfully to diagnose and stage sarcoidosis. 18F-fluorodeoxyglucose (18F-FDG) has been suggested as a positron emission tomography (PET) tracer for sarcoidosis imaging. This study aimed to analyze possible advantages of 18F-FDG-PET over 67Ga citrate scintigraphy during the primary assessment of patients with sarcoidosis. Patients and methods: Twentyfour patients (11 men, 13 women, aged 52 years ±12.4) with histologically proven sarcoidosis were investigated with 18F-FDG and 67Ga citrate. Equipment included a fullring PET scanner (ECAT EXACT HR+, Siemens/CTI, Knoxville TN, USA) and a double-headed gamma camera (ECAM, Siemens, Illinois, USA) for scintigraphy. The mean time difference between the two studies was 6.5 days (range: 5–8 days). Results: There was a significant difference in the detection of pulmonary and nonpulmonary sarcoidosis lesions between planar 67Ga citrate scans and 18F-FDG-PET images (<0.0021). A total of 64 lesions were detected with 67Ga citrate scans in the thorax and elsewhere with a mean of 2.6 lesions (4%) per patient, while 85 lesions were found with 18F-FDG-PET, with a mean of 3.5 lesions (4.1%) per patient. There was complete agreement between 18F-FDG and 67Ga citrate in thoracic manifestations in four (16.6%) patients, and in non-thoracic manifestations in five (20.8%) patients. The interobserver variability showed a kappa value of 0.79. Conclusion: 67Ga citrate and 18F-FDG are useful tracers for diagnostic evaluation of thoracic sarcoidosis. 18F-FDG seems to be more suitable for imaging the mediastinum, the bi-hilar lymph nodes, the posterior regions of the lungs and non-thoracic lesions. Further prospective studies are needed to clarify the role of both tracers in early diagnosis and staging of sarcoidosis, and to resolve questions concerning medical treatment and follow-up.

Microbial enzymes used in prodrug activation for cancer therapy: Insights and future perspectives

2020 ◽  
Vol 21 ◽  
Author(s):  
Rakhi Dhankhar ◽  
Anubhuti Kawatra ◽  
Aparajita Mohanty ◽  
Pooja Gulati
Keyword(s):  
Purine Nucleoside Phosphorylase ◽  
Cytosine Deaminase ◽  
Therapeutic Index ◽  
Enzyme Prodrug Therapy ◽  
Prodrug Activation ◽  
Microbial Enzymes ◽  
High Productivity ◽  
Delivery Vector ◽  
Exogenous Enzymes ◽  
Activation Therapy

Abstract:: Enzyme prodrug therapy has gained momentum in the recent years due to their ability to improve therapeutic index (benefits versus toxic side-effects) and efficacy of chemotherapy in cancer treatment. Inactive prodrugs used in this system are converted into active anti-cancerous drugs by enzymes, specifically within the tumor cells. This therapy involves three components namely prodrug, enzyme and gene delivery vector. Past reports have clearly indicated that the choice of enzyme used, is the major determinant for the success of this therapy. Generally, enzymes from non-human sources are employed to avoid off-target toxicity. Exogenous enzymes also give a better control to the clinician regarding the calibration of treatment by site-specific initiation. Amongst these exo-enzymes, microbial enzymes are preferred due to their high productivity, stability and ease of manipulation. The present review focuses on the commonly used microbial enzymes particularly cytosine deaminase, nitroreductase, carboxypeptidase, purine nucleoside phosphorylase in prodrug activation therapy. Various aspects viz. source of the enzymes, types of cancer targeted, mode of action and efficacy of the enzyme/prodrug system, efficient vectors used and recent research developments of each of these enzymes are comprehensively elaborated. Further, the results of the clinical trials and various strategies to improve their clinical applicability are also discussed.

scholarly journals A novel PET tracer 18F-deoxy-thiamine: synthesis, metabolic kinetics, and evaluation on cerebral thiamine metabolism status

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Changpeng Wang ◽  
Siwei Zhang ◽  
Yuefei Zou ◽  
Hongzhao Ma ◽  
Donglang Jiang ◽  
...  
Keyword(s):  
High Performance ◽  
Specific Activity ◽  
High Accumulation ◽  
Metabolic Kinetics ◽  
Thiamine Metabolism ◽  
Pet Tracer ◽  
The Status ◽  
The Brain

Abstract Background Some neuropsychological diseases are associated with abnormal thiamine metabolism, including Korsakoff–Wernicke syndrome and Alzheimer’s disease. However, in vivo detection of the status of brain thiamine metabolism is still unavailable and needs to be developed. Methods A novel PET tracer of 18F-deoxy-thiamine was synthesized using an automated module via a two-step route. The main quality control parameters, such as specific activity and radiochemical purity, were evaluated by high-performance liquid chromatography (HPLC). Radiochemical concentration was determined by radioactivity calibrator. Metabolic kinetics and the level of 18F-deoxy-thiamine in brains of mice and marmosets were studied by micro-positron emission tomography/computed tomography (PET/CT). In vivo stability, renal excretion rate, and biodistribution of 18F-deoxy-thiamine in the mice were assayed using HPLC and γ-counter, respectively. Also, the correlation between the retention of cerebral 18F-deoxy-thiamine in 60 min after injection as represented by the area under the curve (AUC) and blood thiamine levels was investigated. Results The 18F-deoxy-thiamine was stable both in vitro and in vivo. The uptake and clearance of 18F-deoxy-thiamine were quick in the mice. It reached the max standard uptake value (SUVmax) of 4.61 ± 0.53 in the liver within 1 min, 18.67 ± 7.04 in the kidney within half a minute. The SUV dropped to 0.72 ± 0.05 and 0.77 ± 0.35 after 60 min of injection in the liver and kidney, respectively. After injection, kidney, liver, and pancreas exhibited high accumulation level of 18F-deoxy-thiamine, while brain, muscle, fat, and gonad showed low accumulation concentration, consistent with previous reports on thiamine distribution in mice. Within 90 min after injection, the level of 18F-deoxy-thiamine in the brain of C57BL/6 mice with thiamine deficiency (TD) was 1.9 times higher than that in control mice, and was 3.1 times higher in ICR mice with TD than that in control mice. The AUC of the tracer in the brain of marmosets within 60 min was 29.33 ± 5.15 and negatively correlated with blood thiamine diphosphate levels (r = − 0.985, p = 0.015). Conclusion The 18F-deoxy-thiamine meets the requirements for ideal PET tracer for in vivo detecting the status of cerebral thiamine metabolism.

scholarly journals Human Biodistribution and Radiation Dosimetry of the P-Glycoprotein Radiotracer [11C]Metoclopramide

2021 ◽  
Author(s):  
Martin Bauer ◽  
Sandra Barna ◽  
Matthias Blaickner ◽  
Konstantin Prosenz ◽  
Karsten Bamminger ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Healthy Volunteers ◽  
Effective Dose ◽  
Left Kidney ◽  
Whole Body ◽  
Red Bone Marrow ◽  
Body Distribution ◽  
P Glycoprotein ◽  
Pet Tracer ◽  
Male Subjects

Abstract Purpose To assess in healthy volunteers the whole-body distribution and dosimetry of [11C]metoclopramide, a new positron emission tomography (PET) tracer to measure P-glycoprotein activity at the blood-brain barrier. Procedures Ten healthy volunteers (five women, five men) were intravenously injected with 387 ± 49 MBq of [11C]metoclopramide after low dose CT scans and were then imaged by whole-body PET scans from head to upper thigh over approximately 70 min. Ten source organs (brain, thyroid gland, right lung, myocardium, liver, gall bladder, left kidney, red bone marrow, muscle and the contents of the urinary bladder) were manually delineated on whole-body images. Absorbed doses were calculated with QDOSE (ABX-CRO) using the integrated IDAC-Dose 2.1 module. Results The majority of the administered dose of [11C]metoclopramide was taken up into the liver followed by urinary excretion and, to a smaller extent, biliary excretion of radioactivity. The mean effective dose of [11C]metoclopramide was 1.69 ± 0.26 μSv/MBq for female subjects and 1.55 ± 0.07 μSv/MBq for male subjects. The two organs receiving the highest radiation doses were the urinary bladder (10.81 ± 0.23 μGy/MBq and 8.78 ± 0.89 μGy/MBq) and the liver (6.80 ± 0.78 μGy/MBq and 4.91 ± 0.74 μGy/MBq) for female and male subjects, respectively. Conclusions [11C]Metoclopramide showed predominantly renal excretion, and is safe and well tolerated in healthy adults. The effective dose of [11C]metoclopramide was comparable to other 11C-labeled PET tracers.

scholarly journals Dealing with PET radiometabolites

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Krishna Kanta Ghosh ◽  
Parasuraman Padmanabhan ◽  
Chang-Tong Yang ◽  
Sachin Mishra ◽  
Christer Halldin ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Distribution Patterns ◽  
The Body ◽  
Analysis Process ◽  
Pet Tracer ◽  
Positron Emission ◽  
Structural Identity ◽  
Available Technology ◽  
Living Organisms ◽  
Entire Amount

Abstract Positron emission tomography (PET) offers the study of biochemical, physiological, and pharmacological functions at a cellular and molecular level. The performance of a PET study mostly depends on the used radiotracer of interest. However, the development of a novel PET tracer is very difficult, as it is required to fulfill a lot of important criteria. PET radiotracers usually encounter different chemical modifications including redox reaction, hydrolysis, decarboxylation, and various conjugation processes within living organisms. Due to this biotransformation, different chemical entities are produced, and the amount of the parent radiotracer is declined. Consequently, the signal measured by the PET scanner indicates the entire amount of radioactivity deposited in the tissue; however, it does not offer any indication about the chemical disposition of the parent radiotracer itself. From a radiopharmaceutical perspective, it is necessary to quantify the parent radiotracer’s fraction present in the tissue. Hence, the identification of radiometabolites of the radiotracers is vital for PET imaging. There are mainly two reasons for the chemical identification of PET radiometabolites: firstly, to determine the amount of parent radiotracers in plasma, and secondly, to rule out (if a radiometabolite enters the brain) or correct any radiometabolite accumulation in peripheral tissue. Besides, radiometabolite formations of the tracer might be of concern for the PET study, as the radiometabolic products may display considerably contrasting distribution patterns inside the body when compared with the radiotracer itself. Therefore, necessary information is needed about these biochemical transformations to understand the distribution of radioactivity throughout the body. Various published review articles on PET radiometabolites mainly focus on the sample preparation techniques and recently available technology to improve the radiometabolite analysis process. This article essentially summarizes the chemical and structural identity of the radiometabolites of various radiotracers including [11C]PBB3, [11C]flumazenil, [18F]FEPE2I, [11C]PBR28, [11C]MADAM, and (+)[18F]flubatine. Besides, the importance of radiometabolite analysis in PET imaging is also briefly summarized. Moreover, this review also highlights how a slight chemical modification could reduce the formation of radiometabolites, which could interfere with the results of PET imaging. Graphical abstract

scholarly journals Gene-Directed Enzyme Prodrug Therapy by Dendrimer-Like Mesoporous Silica Nanoparticles against Tumor Cells

Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1298
Author(s):  
Vicente Candela-Noguera ◽  
Gema Vivo-Llorca ◽  
Borja Díaz de Greñu ◽  
María Alfonso ◽  
Elena Aznar ◽  
...  
Keyword(s):  
Cell Death ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Tumor Cells ◽  
Mesoporous Silica Nanoparticles ◽  
Combined Treatment ◽  
Bond Rupture ◽  
Enzyme Prodrug Therapy ◽  
Bacterial Gene ◽  
Reducing Environment

We report herein a gene-directed enzyme prodrug therapy (GDEPT) system using gated mesoporous silica nanoparticles (MSNs) in an attempt to combine the reduction of side effects characteristic of GDEPT with improved pharmacokinetics promoted by gated MSNs. The system consists of the transfection of cancer cells with a plasmid controlled by the cytomegalovirus promoter, which promotes β-galactosidase (β-gal) expression from the bacterial gene lacZ (CMV-lacZ). Moreover, dendrimer-like mesoporous silica nanoparticles (DMSNs) are loaded with the prodrug doxorubicin modified with a galactose unit through a self-immolative group (DOXO-Gal) and modified with a disulfide-containing polyethyleneglycol gatekeeper. Once in tumor cells, the reducing environment induces disulfide bond rupture in the gatekeeper with the subsequent DOXO-Gal delivery, which is enzymatically converted by β-gal into the cytotoxic doxorubicin drug, causing cell death. The combined treatment of the pair enzyme/DMSNs-prodrug are more effective in killing cells than the free prodrug DOXO-Gal alone in cells transfected with β-gal.

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