Klaus Vieweg/Michael Winkler (Hrsg.): Bildung und Freiheit. Ein vergessener Zusammenhang. Paderborn: Schöningh, 2012[Rezension]

Rezension von: Klaus Vieweg/Michael Winkler (Hrsg.): Bildung und Freiheit. Ein vergessener Zusammenhang. Paderborn: Schöningh, 2012, 248 S., EUR 29,90

Human biodistribution and radiation dosimetry of novel PET probes targeting the deoxyribonucleoside salvage pathway

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

Molecular imaging in oncology: the acceptance of PET/CT and the emergence of MR/PET imaging

In the last decade, PET-only systems have been phased out and replaced with PET-CT systems. This merger of a functional and anatomical imaging modality turned out to be extremely useful in clinical practice. Currently, PET-CT is a major diagnostic tool in oncology. At the dawn of the merger of MRI and PET, another breakthrough in clinical imaging is expected. The combination of these imaging modalities is challenging, but has particular features such as imaging biological processes at the same time in specific body locations

Molecular imaging in oncology: the acceptance of PET/CT and the emergence of MR/PET imaging

In the last decade, PET-only systems have been phased out and replaced with PET-CT systems. This merger of a functional and anatomical imaging modality turned out to be extremely useful in clinical practice. Currently, PET-CT is a major diagnostic tool in oncology. At the dawn of the merger of MRI and PET, another breakthrough in clinical imaging is expected. The combination of these imaging modalities is challenging, but has particular features such as imaging biological processes at the same time in specific body locations

The incidence of thyroid cancer in focal hypermetabolic thyroid lesions

BackgroundThe clinical significance of incidental thyroid abnormalities discovered in fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) (FDG PET/CT) studies remains controversial. The aim of this large retrospective study was to (a) determine the prevalence of focal F-FDG thyroid uptake on whole-body F-FDG PET/CT studies carried out for nonthyroid cancers and (b) to test whether intense focal F-FDG thyroid uptake is associated with malignancy.Materials and methodsA total of 11 921 F-FDG PET/CT studies in 6216 patients carried out at our institution between January 2012 and December 2014 were analyzed. We retrospectively reviewed the medical records of these patients. Eight hundred and forty-five/6216 (13.6%) patients had a thyroid incidentaloma on the basis of the clinical F-FDG PET/CT report. One hundred and sixty/845 (18.9%) of these underwent ultrasound and 98 (61.3%) of these underwent a fine-needle aspiration (FNA). Twenty-six of these 98 (26.5%) patients underwent thyroidectomy. Thyroid lesion and background standardized uptake value (SUVs) for each patient were measured upon review of the F-FDG PET/CT study. We measured maximum standardized uptake value (SUVmax), thyroid to background TL/TBG, thyroid to bloodpool TL/BP and thyroid to liver TL/L ratios in benign and malignant lesions. Receiver operating curves were calculated to determine optimal cut-off values between malignant and benign lesions.ResultsTwenty-one of the 98 patients who underwent FNA biopsy or thyroidectomy had malignant disease (21.4%). Malignant lesions had significantly higher thyroid lesion SUVmax, TL/TBG, TL/BP, and TL/L than benign nodules. The receiver operating curves derived cut-off ratio TL/TBG of more than 2.0 differentiated benign from malignant lesions best with a specificity and sensitivity of 0.76 and 0.88, respectively.ConclusionThe incidence of malignancy in biopsied focal hypermetabolic thyroid lesions is 21.4%. Lesions on F-FDG PET/CT studies, with a ratio TL/TBG more than 2.0, warrant further work-up with ultrasound and FNA to exclude malignancy

Human Biodistribution and Radiation Dosimetry of 18

18F-clofarabine, a nucleotide purine analog, is a substrate for deoxycytidine kinase (dCK), a key enzyme in the deoxyribonucleoside salvage pathway. 18F-clofarabine might be used to measure dCK expression and thus serve as a predictive biomarker for tumor responses to dCK-dependent prodrugs or small-molecule dCK inhibitors, respectively. As a prerequisite for clinical translation, we determined the human whole-body and organ dosimetry of 18F-clofarabine. Methods: Five healthy volunteers were injected intravenously with 232.4 ± 1.5 MBq of 18F-clofarabine. Immediately after tracer injection, a dynamic scan of the entire chest was acquired for 30 min. This was followed by 3 static whole-body scans at 45, 90, and 135 min after tracer injection. Regions of interest were drawn around multiple organs on the CT scan and copied to the PET scans. Organ activity was determined and absorbed dose was estimated with OLINDA/EXM software. Results: The urinary bladder (critical organ), liver, kidney, and spleen exhibited the highest uptake. For an activity of 250 MBq, the absorbed doses in the bladder, liver, kidney, and spleen were 58.5, 6.6, 6.3, and 4.3 mGy, respectively. The average effective dose coefficient was 5.1 mSv. Conclusion: Our results hint that 18F-clofarabine can be used safely in humans to measure tissue dCK expression. Future studies will determine whether 18F-clofarabine may serve as a predictive biomarker for responses to dCK-dependent prodrugs or small-molecule dCK inhibitors