Trial reportEuropean journal of nuclear medicine and molecular imaging2011
Human biodistribution and radiation dosimetry of novel PET probes targeting the deoxyribonucleoside salvage pathway.
Trial report in European journal of nuclear medicine and molecular imaging, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
- Trial
- Structure-guided engineering of human thymidine kinase 2 as a positron emission tomography reporter gene for enhanced phosphorylation of non-natural thymidine analog reporter probe.The Journal of biological chemistry · 2012Trial
- Landscape of targets within nucleoside metabolism for the modification of immune responses.Frontiers in oncology · 2025Review
- Imaging cellular immunotherapies and immune cell biomarkers: from preclinical studies to patients.Journal for immunotherapy of cancer · 2022Review
- Radionuclide Imaging of Cytotoxic Immune Cell Responses to Anti-Cancer Immunotherapy.Biomedicines · 2022Review
- Analysis of capecitabine metabolites in conjunction with digital autoradiography in a murine model of pancreatic cancer suggests extensive drug penetration through the tumor.Pharmacology research & perspectives · 2022Article
- Molecular Immune Targeted Imaging of Tumor Microenvironment.Nanotheranostics · 2022Review
- Biodistribution of a Mitochondrial Metabolic Tracer, [Molecular imaging · 2022Article
- Predicting Gemcitabine Delivery byJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2021Article
- Noninvasive Imaging of Cancer Immunotherapy.Nanotheranostics · 2021Review
- Article
- [Cancers · 2019Article
- Imaging of T-cells and their responses during anti-cancer immunotherapy.Theranostics · 2019Review
- Imaging of Activated T Cells as an Early Predictor of Immune Response to Anti-PD-1 Therapy.Cancer research · 2019Article
- Article
- Noninvasive PET Imaging of T cells.Trends in cancer · 2018Review
- In Vitro and In Vivo Comparison of Gemcitabine and the Gemcitabine Analog 1-(2'-deoxy-2'-fluoroarabinofuranosyl) Cytosine (FAC) in Human Orthotopic and Genetically Modified Mouse Pancreatic Cancer Models.Molecular imaging and biology · 2017Article
- A PET Imaging Strategy to Visualize Activated T Cells in Acute Graft-versus-Host Disease Elicited by Allogenic Hematopoietic Cell Transplant.Cancer research · 2017Article
- Advancing Immune and Cell-Based Therapies Through Imaging.Molecular imaging and biology · 2017Review
- Harnessing Preclinical Molecular Imaging to Inform Advances in Personalized Cancer Medicine.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2017Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
purposeDeoxycytidine kinase (dCK) is a rate-limiting enzyme in deoxyribonucleoside salvage, a metabolic pathway involved in the production and maintenance of a balanced pool of deoxyribonucleoside triphosphates (dNTPs) for DNA synthesis. dCK phosphorylates and therefore activates nucleoside analogs such as cytarabine, gemcitabine, decitabine, cladribine, and clofarabine that are used routinely in cancer therapy. Imaging probes that target dCK might allow stratifying patients into likely responders and nonresponders with dCK-dependent prodrugs. Here we present the biodistribution and radiation dosimetry of three fluorinated dCK substrates, (18)F-FAC, L: -(18)F-FAC, and L: -(18)F-FMAC, developed for positron emission tomography (PET) imaging of dCK activity in vivo.
methodsPET studies were performed in nine healthy human volunteers, three for each probe. After a transmission scan, the radiopharmaceutical was injected intravenously and three sequential emission scans acquired from the base of the skull to mid-thigh. Regions of interest encompassing visible organs were drawn on the first PET scan and copied to the subsequent scans. Activity in target organs was determined and absorbed dose estimated with OLINDA/EXM. The standardized uptake value was calculated for various organs at different times.
resultsRenal excretion was common to all three probes. Bone marrow had higher uptake for L: -(18)F-FAC and L: -(18)F-FMAC than (18)F-FAC. Prominent liver uptake was seen in L: -(18)F-FMAC and L: -(18)F-FAC, whereas splenic activity was highest for (18)F-FAC. Muscle uptake was also highest for (18)F-FAC. The critical organ was the bladder wall for all three probes. The effective dose was 0.00524, 0.00755, and 0.00910 mSv/MBq for (18)F-FAC, L: -(18)F-FAC, and L: -(18)F-FMAC, respectively.
conclusionThe biodistribution of (18)F-FAC, L: -(18)F-FAC, and L: -(18)F-FMAC in humans reveals similarities and differences. Differences may be explained by different probe affinities for nucleoside transporters, dCK, and catabolic enzymes such as cytidine deaminase (CDA). Dosimetry demonstrates that all three probes can be used safely to image the deoxyribonucleoside salvage pathway in humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.