[en] The aim of this study was to evaluate the use of ¹²⁴I positron emission tomography (PET) to determine the dosimetry of radioiodine therapy in hyperthyroidism and thyroid cancer. Phantom studies to assess the accuracy of PET were performed using an EEC phantom with spheres of different diameters filled with 3-30 MBq of ¹²⁴I. Patient dosimetry was derived from PET data obtained 1-13 days after simultaneous oral administration of a therapeutic dose of ¹³¹I and a diagnostic dose of ¹²⁴I. The obtained data were compared with findings from intratherapeutic probe measurements and clinical outcome. The phantom studies confirmed that ¹²⁴I can be quantitated by PET (imprecision ≤10%), and volumetry is feasible for nodules <13 mm (imprecision ≤20%). Any influence of contamination with ¹²³I or the simultaneous administration of ¹³¹I on the accuracy of the PET quantification and the probe measurements was ruled out by phantom measurements with solutions of ¹³¹I, ¹²⁴I and¹²³I in various ratios. In autonomous nodular goitres, radioiodine uptake measured by PET varied from 25.4% to 64.3% and was not significantly different from that obtained by a scintillation probe (24.1%-73.1%, correlation coefficient r=0.91). Comparison of uptake and effective half-life in normal tissue versus autonomous nodules revealed significant differences in uptake but not in effective half-life [uptake 2.0-8.3 kBq/(ml x MBq) in normal tissue vs 12.6-29.3 kBq/(ml x MBq) in nodules; half-life 97.8-156.7 h in normal tissue vs 73.3-192.3 h in nodules]. Calculated radiation doses ranged between 177 and 633 Gy for autonomous nodules and between 47 and 126 Gy for normal tissue. In thyroid cancer patients, doses between 350 and 1,420 Gy were achieved in thyroid remnants and between 70 and 170 Gy in tumour metastases. It is concluded that ¹²⁴I and PET are suitable for evaluation of the dosimetry of radioiodine therapy in benign and malignant thyroid diseases. The applied technique might be particularly useful for quantitative dose-response studies in radioiodine treatment and further investigations of stunning phenomena. (orig.)

[en] This study led to synthesize β-5-(¹⁸F)FAZA and evaluate it's hypoxia selective uptake in tumor cells. A study to evaluate whether its uptake is facilitated by natural nucleoside transporters is currently underway

[en] The aim of this study was to evaluate the use of [¹⁸F]fluorothymidine (FLT) as a positron emission tomography (PET) tracer for the diagnosis of breast cancer. To this end, 12 patients with 14 primary breast cancer lesions (T2-T4) were studied by FLT-PET. For comparison, [¹⁸F]fluorodeoxyglucose (FDG) PET scans were performed in six patients. Thirteen of the 14 primary tumours demonstrated focally increased FLT uptake (SUV_mean=3.4±1.1). Seven out of eight patients with histologically proven axillary lymph node metastases showed focally increased FLT uptake in the corresponding areas (SUV_mean=2.4±1.2). The lowest SUV (mean =0.7) was observed in one of two inflammatory cancers. The contrast between primary tumours or metastases and surrounding tissue was high in most cases. In direct comparison to FDG-PET, the SUVs of primary tumours (5/6) and axillary lymph node metastases (3/4) were lower in FLT-PET (SUV_FLT: 3.2 vs SUV_FDG: 4.7 in primary tumours and SUV_FLT: 2.9 vs SUV_FDG: 4.6 in lymph node metastases). Since FLT uptake in surrounding breast tissue was also lower, tumour contrast was comparable to that with FDG. It is of note that normal FLT uptake was very low in the mediastinum, resulting in a higher tumour-to-mediastinum ratio as compared to FDG (P=0.03). FLT-PET is suitable for the diagnosis of primary breast cancer and locoregional metastases. High image contrast may facilitate the detection of small foci, especially in the mediastinum. (orig.)

[en] For ¹⁸F-labelling of aromatic amino acids such as tyrosine and DOPA simple and efficient procedures have been under development for quite a while. The direct introduction of ¹⁸F using [¹⁸F]fluoride can principally be realized by nucleophilic aromatic substitution (S_NAr). However, this requires the presence of an appropriate leaving group and an auxiliary substituent, which is able to reduce the electron density of the benzene ring. Furthermore, this auxiliary substituent should be removable easily after the introduction of ¹⁸F. The electron-withdrawing formyl substituent meets both requirements. It facilitates nucleophilic attack in the ortho and/or para position and is easily removed in a decarbonylation reaction mediated by Wilkinson's catalyst (RhCl(PPh₃)₃). In order to evaluate the reaction conditions for a possible synthesis of 2-[¹⁸F]fluoro-5-hydroxyphenylalanine ([¹⁸F]-m-tyrosine), 2-[¹⁸F]fluoro-4-hydroxyphenylalanine ([¹⁸F]-p-tyrosine) or 2-[¹⁸F]fluoro-4,5-hydroxyphenylalanine ([¹⁸F]FDOPA), the dependence of the decarbonylation reaction on solvent, temperature, reaction time and catalyst concentration was studied using appropriate model compounds. Optimum yields of 81%, 89% and 88% could be achieved using benzonitrile as solvent and 2 M equivalents of RhCl(PPh₃)₃ (based on labelling precursor) at 150 ^oC reaction temperature within 20 min reaction time for compounds modelling [¹⁸F]-m-tyrosine, [¹⁸F]-p-tyrosine and [¹⁸F]FDOPA, respectively

[en] Iodine-124 was produced via the ¹²⁴Te(p,n)¹²⁴I reaction by 15 MeV proton irradiation of an in-house solid mass tellurium dioxide target, using the Tuebingen PETtrace^TM (General Electric Medical Systems) cyclotron. 1-(2-Deoxy-β-D-ribofuranosyl)-2,4-difluoro-5-iodobenzene (dRFIB), a stable, non-polar thymidine mimic nucleoside, was synthesized in 5 steps following a literature method, for radioiodination with [¹²⁴I] iodide via isotope exchange in the presence of copper sulphate and ammonium sulphate in methanol-water. The radiolabelling procedure was optimized with respect to temperature, amount of dRFIB, amount of sodium hydroxide and reaction time, to produce radiochemical yields of up to 85% with a 1-h reaction at 140 ^oC. With routine I-124 production of 30 MBq/run, relatively high specific activities, approaching 100 MBq/mmol, can be expected. The activation energy for dRFIB radioiodination was calculated from temperature-time RCY data to be approximately 100 kJ/mol using no-carrier-added [¹²⁴I]iodide

[en] The use of dynamic susceptibility contrast (DSC) perfusion and ¹¹C-methionine positron emission tomography (MET-PET) for glioma grading is currently not standardized. The purpose of this study was to identify regions of interest (ROIs) that enable the best performance and clinical applicability in both methods, as well as to evaluate the complementarity of DSC perfusion and MET-PET in spatial hotspot definition. In 41 patient PET/MRI datasets, different ROIs were drawn: in T2-hyperintense tumour, in T2-hyperintense tumour and adjacent oedema and in tumour areas with contrast enhancement, altered perfusion or pathological radiotracer uptake. The performance of DSC perfusion and MET-PET using the different ROIs to distinguish high- and low-grade gliomas was assessed. The spatial overlap of hotspots identified by DSC perfusion and MET-PET was assessed visually. ROIs in T2 fluid attenuated inversion recovery (FLAIR) sequence-hyperintense tumour revealed the most significant differences between high- and low-grade gliomas and reached the highest diagnostic performance in both DSC perfusion (p = 0.046; area under the curve = 0.74) and MET-PET (p = 0.007; area under the curve = 0.80). The combination of methods yielded an area under the curve of 0.80. Hotspots were completely overlapped in one half of the patients, partially overlapped in one third of the patients and present in only one method in approximately 20% of the patients. For multi-parametric examinations with DSC perfusion and MET-PET, we recommend an ROI definition based on T2-hyperintense tumour. DSC perfusion and MET-PET contain complementary information concerning the spatial hotspot definition. (orig.)

[en] Autoradiolysis describes the degradation of radioactively labeled compounds due to the activity of the labeled compounds themselves. It scales with activity concentration and is of importance for high activity and microfluidic PET tracer synthesis. This study shows that microfluidic devices can be shaped to reduce autoradiolysis by geometric exclusion of positron interaction. A model is developed and confirmed by demonstrating in-capillary storage of non-stabilized [¹⁸F]FDG (2-[¹⁸F]Fluoro-2-deoxy-D-glucose) at max. 23 GBq/ml while maintaining >90% radiochemical purity over 14 h. - Highlights: ► Autoradiolysis reduction of [¹⁸F]FDG at up to 23 GBq/ml utilizing small vessel geometries instead of stabilizers or scavengers. ► Theoretical model on positron interaction and autoradiolysis in radiopharmaceuticals. ► Evidence suggest microfluidics to work for high activity PET tracer batch production. ► New vessel design concepts for PET tracer production and storage.

[en] Prostate-specific membrane antigen (PSMA) is expressed ubiquitously on the membrane of most prostate tumors and its metastasis. While PET/CT using "1"1C-choline was considered as the gold standard in the staging of prostate cancer, PET with radiolabelled PSMA ligands was introduced into the clinic in recent years. Our aim was to compare the PSMA ligand "6"8Ga-PSMA-11 with "1"1C-choline in patients with primary and recurrent prostate cancer. 123 patients underwent a whole-body PET/CT examination using "6"8Ga-PSMA-11 and "1"1C-choline. Suspicious lesions were evaluated visually and semiquantitatively (SUVavg). Out of these, 103 suffered from a confirmed biochemical relapse after prostatectomy and/or radiotherapy (mean PSA level of 4.5 ng/ml), while 20 patients underwent primary staging. In 67 patients with biochemical relapse, we detected 458 lymph nodes suspicious for metastasis. PET using "6"8Ga-PSMA-11 showed a significantly higher uptake and detection rate than "1"1C-choline PET. Also "6"8Ga-PSMA-11 PET identified significantly more patients with suspicious lymph nodes as well as affected lymph nodes regions especially at low PSA levels. Bone lesions suspicious for prostate cancer metastasis were revealed in 36 patients' biochemical relapse. Significantly more bone lesions were detected by "6"8Ga-PSMA-11, but only 3 patients had only PSMA-positive bone lesions. Nevertheless, we detected also 29 suspicious lymph nodes and 8 bone lesions, which were only positive as per "1"1C-choline PET. These findings led to crucial differences in the TNM classification and the identification of oligometastatic patients. In the patients who underwent initial staging, all primary tumors showed uptake of both tracers. Although significantly more suspicious lymph nodes and bone lesions were identified, only 2 patients presented with bone lesions only detected by "6"8Ga-PSMA-11 PET. Thus, PET using "6"8Ga-PSMA-11 showed a higher detection rate than "1"1C-choline PET for lymph nodes as well as bone lesions. However, we found lymph nodes and bone lesions which were not concordant applying both tracers. (orig.)

[en] Introduction: Radiolabeled 2-nitroimidazoles (azomycins) are a prominent class of biomarkers for PET imaging of hypoxia. [¹⁸F]Fluoro-azomycin-α-arabinoside ([¹⁸F]FAZA) – already in clinical use – may be seen as α-configuration nucleoside, but enters cells only via diffusion and is not transported by cellular nucleoside transporters. To enhance image contrast in comparison to [¹⁸F]FAZA our objective was to ¹⁸F-radiolabel an azomycin-2´-deoxyriboside with β-configuration ([¹⁸F]FAZDR, [¹⁸F]-β-8) to mimic nucleosides more closely and comparatively evaluate it versus [¹⁸F]FAZA. Methods: Precursor and cold standards for [¹⁸F]FAZDR were synthesized from methyl 2-deoxy-D-ribofuranosides α- and β-1 in 6 steps yielding precursors α- and β-5. β-5 was radiolabeled in a GE TRACERlab FX_F-N synthesizer in DMSO and deprotected with NH₄OH to give [¹⁸F]FAZDR ([¹⁸F]-β-8). [¹⁸F]FAZA or [¹⁸F]FAZDR was injected in BALB/c mice bearing CT26 colon carcinoma xenografts, PET scans (10 min) were performed after 1, 2 and 3 h post injection (p.i.). On a subset of mice injected with [¹⁸F]FAZDR, we analyzed biodistribution. Results: [¹⁸F]FAZDR was obtained in non-corrected yields of 10.9 ± 2.4% (9.1 ± 2.2 GBq, n = 4) 60 min EOB, with radiochemical purity >98% and specific activity >50 GBq/μmol. Small animal PET imaging showed a decrease in uptake over time for both [¹⁸F]FAZDR (1 h p.i.: 0.56 ± 0.22% ID/cc, 3 h: 0.17 ± 0.08% ID/cc, n = 9) and [¹⁸F]FAZA (1 h: 1.95 ± 0.59% ID/cc, 3 h: 0.87 ± 0.55% ID/cc), whereas T/M ratios were significantly higher for [¹⁸F]FAZDR at 1 h (2.76) compared to [¹⁸F]FAZA (1.69, P < 0.001), 3 h p.i. ratios showed no significant difference. Moreover, [¹⁸F]FAZDR showed an inverse correlation between tracer uptake in carcinomas and oxygen breathing, while muscle tissue uptake was not affected by switching from air to oxygen. Conclusions: First PET imaging results with [¹⁸F]FAZDR showed advantages over [¹⁸F]FAZA regarding higher tumor contrast at earlier time points p.i. Availability of precursor and cold fluoro standard together with high output radiosynthesis will allow for a more detailed quantitative evaluation of [¹⁸F]FAZDR, especially with regard to mechanistic studies whether active transport processes are involved, compared to passive diffusion as observed for [¹⁸F]FAZA.

[en] ["1"8F]FAZA is a PET biomarker with great potential for imaging tumor hypoxia. Aim of our study was to compare ["1"8F]FAZA uptake in mice with subcutaneous exogenous CT26 colon carcinomas and endogenous polyoma middle-T (PyV-mT) mammary carcinomas and to analyze the influence of different breathing protocols in CT26 colon carcinomas as well as the reversibility or irreversibility of ["1"8F]FAZA uptake. We injected subcutaneous CT26 colon carcinoma or polyomavirus middle-T (PyV-mT) mammary carcinoma-bearing mice intravenously with"1"8F-FAZA and performed PET scans 1-3 h post injection (p.i.). To analyze the impact of oxygen supply in CT26 carcinomas we used three different breathing protocols: (P0) air; (P1) 100% oxygen 1 h prior injection until 3 h p.i.; (P2) 100% oxygen breathing starting 2 min prior tracer injection until 1 h p.i. and during the PET scans; mice were breathing air between the 2 h and 3 h 10 min static scans. Normalized PET images were analyzed by using defined regions of interest. Finally, some mice were dissected for pimonidazole immunohistochemistry. There was no difference in"1"8F-FAZA uptake 1-3 h p.i. between the two carcinoma types (CT26: 1.58 ± 0.45%ID/cc; PyV-mT: 1.47 ± 0.89%ID/cc, 1 h p.i., tumor size < 0.5 cm"3). We measured a significant tracer clearance, which was more pronounced in muscle tissue (P0). The ["1"8F]FAZA tumor-to-muscle-ratios in CT26 colon carcinoma-bearing mice 2 h and 3 h, but not 1 h p.i. were significantly higher when the mice breathed air (P0: 3.56 ± 0.55, 3 h) compared to the oxygen breathing protocols (P1: 2.45 ± 0.58; P2: 2.77 ± 0.42, 3 h). Surprisingly, the breathing protocols P1 and P2 showed no significant differences in T/M ratios, thus indicating that the crucial ["1"8F]FAZA uptake phase is during the first hour after ["1"8F]FAZA injection. Importantly, the muscle clearance was not affected by the different oxygen breathing conditions while the tumor clearance was lower when mice were breathing air. Exogenous CT26 colon carcinomas and endogenous polyoma middle-T (PyV-mT) mammary carcinomas showed no differences in ["1"8F]FAZA uptake 1-3 h p.i. Our analysis using various breathing protocols with air (P0) and with pure oxygen (P1, P2) clearly indicate that ["1"8F]FAZA is an appropriate PET biomarker for in vivo analysis of hypoxia revealing an enhanced tracer uptake in tumors with reduced oxygen supply. ["1"8F]FAZA uptake was independent of tumor-type