Preclinical acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging studies of [18F]fluorocholine in mice

Silveira, Marina Bicalho; Ferreira, Soraya M. Z. M. D.; Nascimento, Leonardo Tafas Constantino do; Costa, Flávia M.; Mendes, Bruno Melo; Ferreira, Andréa Vidal; Malamut, Carlos; Silva, Juliana B.; Mamede, Marcelo

doi:10.1016/j.apradiso.2016.07.021

Cited by 8 publications

(5 citation statements)

References 32 publications

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“…The [ 18 F]FCh tracer is routinely used in the clinics as a successful tool for cancer imaging. However, to the best of our knowledge, despite copious amount of in vitro data in PC-3 cells and ex vivo biodistribution studies, there is no report in the literature of a satisfactory tumor visualization in murine PC-3 xenograft model using [ 18 F]FCh. − This strongly suggests, that in murine PC-3 xenograft model, the choline transport mechanisms become saturated at doses necessary for imaging even with high-molar-activity tracers routinely used in humans. The imaging data in the literature as well as our SPECT and PET experiments lead us to a conclusion that a bigger animal model is necessary for successful in vivo imaging with tracers targeting choline transport proteins.…”

Section: Resultsmentioning

confidence: 99%

Iodinated Choline Transport-Targeted Tracers

et al. 2020

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We present a novel series of radioiodinated tracers and potential theranostics for diseases accompanied by pathological function of proteins involved in choline transport. Unlike choline analogues labeled with 11C or 18F that are currently used in the clinic, the iodinated compounds described herein are applicable in positron emission tomography, single-photon emission computed tomography, and potentially in therapy, depending on the iodine isotope selection. Moreover, favorable half-lives of iodine isotopes result in much less challenging synthesis by isotope exchange reaction. Six of the described compounds were nanomolar ligands, and the best compound possessed an affinity 100-fold greater than that of choline. Biodistribution data of 125I-labeled ligands in human prostate carcinoma bearing (PC-3) mice revealed two compounds with a biodistribution profile superior to that of [18F]fluorocholine.

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Section: Resultsmentioning

confidence: 99%

Iodinated Choline Transport-Targeted Tracers

et al. 2020

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“…The following parameters were evaluated mortality, clinical observation of animal was performed for sickness symptoms due to treatment. Change in their appearance (piloerection, kyphosis, disheveled fur), behavior (grooming or nesting) and activity (altered exploring) (Silveira et al, 2016).…”

Section: Toxicity Studymentioning

confidence: 99%

Pharmacokinetics Interaction and Biodistribution of 5 Fluorouracil with Radiopharmaceuticals 99mTc Glutathione for Cancer Diagnostic in Mice Cancer Model

Kurniawan

Wibawa

Daruwati

et al. 2019

Indonesian J. Pharm.

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Radiopharmaceutical 99m Tc-Glutathione has been developed for cancer diagnostic in nuclear medicine. Interactions between chemotherapy drugs and radiopharmaceuticals can altered radiopharmaceuticals performance. Drug interaction 5-fluorouracil (5-FU) with a radiopharmaceutical 99m Tc-Glutathione in mice cancer model has been proven in pharmacokinetics study. The biological half-life distribution of 99m Tc-Glutathione for cancer model mice when administrated with 5-FU become longer to 0.340±0.121h if compared with 99m Tc-Glutathione. Biological halflife elimination for cancer model mice given with 99m Tc-Glutathione is 72.712±2.427h. Administration of 5-FU makes the biological half-life elimination of 99m Tc-Glutathione shorter to 17.030±3.459h. Biodistribution study of 5-FU continued with 99m Tc-Glutathione for cancer model mice showed higher physiological uptake in the kidney was observed (39.77±2.70%ID/g) for 99m Tc-Glutathione has lower uptake on kidney (29.55.3.73 %ID/g) with p<0.05. Based on calculation on cancer model mice with colon cancer compared with muscle, shown target/non-target (T/NT) ratio 2.93 for 5-FU continued with 99m Tc-Glutathione has ratio 0.42. Low ratio T/NT may affect to poor organ visualization for cancer diagnosis. Acute toxicity study has shown drugs safety for clinical purpose. The knowledge about chemotherapy drug interaction with a radiopharmaceutical is important to have a correct diagnosis of the patient on clinical application.

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“…Quality control of [ 18 F]FCH included pH, chemical purity, radiochemical identity and purity, residual solvents, radionuclidic identity and purity, bacterial endotoxins, and sterility tests as previously reported. 30…”

Section: Radiopharmaceuticalmentioning

confidence: 99%

18F-Fluorocholine Uptake and Positron Emission Tomography Imaging in Rat Peritoneal Endometriosis

et al. 2018

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Endometriosis is a debilitating disease that still needs surgery to be confirmed. Endometriosis is associated with increased plasma levels of phosphatidylcholines. F-fluorocholine ([F]FCH) is a radiopharmaceutical that is metabolized to phosphatidylcholine inside the cells and can be traced by positron emission tomography (PET). Here we evaluate [F]FCH as a potential tool for the noninvasive diagnosis of peritoneal endometriosis. Adult female Wistar rats had autologous uterine fragments dissected and grafted to the peritoneal wall to model peritoneal endometriosis. Ex vivo biodistribution assay and PET imaging studies were performed 30 minutes after [F]FCH administration. The [F]FCH uptake was 3-fold higher in endometriotic implant tissues than in muscle or peritoneum. Positron emission tomography imaging revealed the grafted uterine tissue in contrast to surrounding structures. Region-of-interest analysis of the reconstructed images showed higher accumulation of [F]FCH by endometriotic lesions, 0.34 (0.04)% of injected dose per gram of tissue (ID/g), in comparison with muscle tissue, 0.08 (0.01)% ID/g. However, sham implants with fat tissue were also detectable in PET imaging. These preliminary findings of [F]FCH uptake by ectopic uterine tissue implants and their localization by PET imaging encourage the future evaluation of this technique to detect small superficial endometriosis lesions in humans. Study protocols need to be further perfected and adapted for tests in women with endometriosis.

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Preclinical acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging studies of [18F]fluorocholine in mice

Cited by 8 publications

References 32 publications

Iodinated Choline Transport-Targeted Tracers

Iodinated Choline Transport-Targeted Tracers

Pharmacokinetics Interaction and Biodistribution of 5 Fluorouracil with Radiopharmaceuticals 99mTc Glutathione for Cancer Diagnostic in Mice Cancer Model

18F-Fluorocholine Uptake and Positron Emission Tomography Imaging in Rat Peritoneal Endometriosis

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