[en] The [¹⁸F]fluoroethyl moiety has been widely utilized in the synthesis of ¹⁸F-labelled compounds. The aim of this work was the reliable synthesis of [¹⁸F]FEtOTf with a novel strategy to increase the reactivity of the commonly used [¹⁸F]FEB and [¹⁸F]FEtOTos. [¹⁸F]FEtOTf and the intermediate [¹⁸F]FEtOH were synthesized in high RCY (78% and 85%, respectively) and purified by SPE. The high potency of [¹⁸F]FEtOTf was shown by the efficient alkylation of the deactivated nucleophile aniline under mild conditions, as well as by the synthesis of [¹⁸F]FEC. - Highlights: • New, high yielding route for rapid preparation of [¹⁸F]FEtOTf. • No distillation or HPLC necessary for purification of intermediates. • High yielding ¹⁸F-fluoroethylation under mild reaction conditions

[en] To examine the relationship between the extent of disease determined by ["6"8Ga]PSMA-HBED-CC-PET/CT and the important clinical measures prostate-specific antigen (PSA), PSA doubling time (PSAdt) and Gleason score. We retrospectively studied the first 155 patients with recurrent prostate cancer (PCA) referred to our university hospital for ["6"8Ga]PSMA-HBED-CC PET/CT. PET/CT was positive in 44 %, 79 % and 89 % of patients with PSA levels of ≤1, 1 - 2 and ≥2 ng/ml, respectively. Patients with high PSA levels showed higher rates of local prostate tumours (p < 0.001), and extrapelvic lymph node (p = 0.037) and bone metastases (p = 0.013). A shorter PSAdt was significantly associated with pelvic lymph node (p = 0.026), extrapelvic lymph node (p = 0.001), bone (p < 0.001) and visceral (p = 0.041) metastases. A high Gleason score was associated with more frequent pelvic lymph node metastases (p = 0.039). In multivariate analysis, both PSA and PSAdt were independent determinants of scan positivity and of extrapelvic lymph node metastases. PSAdt was the only independent marker of bone metastases (p = 0.001). Of 20 patients with a PSAdt <6 months and a PSA ≥2 ng/ml, 19 (95 %) had a positive scan and 12 (60 %) had M1a disease. Of 14 patients with PSA <1 ng/ml and PSAdt >6 months, only 5 (36 %) had a positive scan and 1 (7 %) had M1a disease. ["6"8Ga]PSMA-HBED-CC PET/CT will identify PCA lesions even in patients with very low PSA levels. Higher PSA levels and shorter PSAdt are independently associated with scan positivity and extrapelvic metastases, and can be used for patient selection for ["6"8Ga]PSMA-HBED-CC PET/CT. (orig.)

[en] To determine the frequency of seemingly pathological retroperitoneal uptake in the location of the coeliac ganglia in patients undergoing [⁶⁸Ga]PSMA-HBED PET/CT. The study included 85 men with prostate cancer referred for [⁶⁸Ga]PSMA-HBED PET/CT. The PET/CT scans were evaluated for the local finding in the prostate and the presence of lymph node metastases, distant metastases and coeliac ganglia. The corresponding standardized uptake values (SUV) were determined. SUVmax to background uptake (gluteal muscle SUVmean) ratios were calculated for the ganglia and lymph node metastases. Immunohistochemistry was performed on the ganglia. In 76 of the 85 patients (89.4 %) at least one ganglion with tracer uptake was found. For the ganglia, SUVmax and SUVmax to background SUVmean ratios were 2.97 ± 0.88 and 7.98 ± 2.84 (range 1.57-6.38 and 2.83-30.6), respectively, and 82.8 % of all ganglia showed an uptake ratio of >5.0. For lymph node metastases, SUVmax and SUVmax to background SUVmean ratios were 8.5 ± 7.0 and 23.31 ± 22.23 (range 2.06-35.9 and 5.25-115.8), respectively. In 35 patients (41.2 %), no lymph node metastases were found but tracer uptake was seen in the ganglia. Immunohistochemistry confirmed strong PSMA expression in the ganglia. Coeliac ganglia show a relevant [⁶⁸Ga]PSMA-HBED uptake in most patients and may mimic lymph node metastases. (orig.)

[en] The radioiodinated 3'-fluorothymidine (FLT) analogue 3'-fluoro-5-[¹³¹I]iodo-2'-deoxyuridine ([¹³¹I]FLIdU) was synthesized, with iodine mimicking the methyl group of pyrimidine. [¹³¹I]FLIdU was accessible by direct electrophilic iodination using Iodogen as oxidant. Optimized amounts of the oxidant allowed radiochemical yields of about 70% after a reaction time of 10 min in an aqueous buffer medium at 90^oC. The uptake of [¹³¹I]FLIdU in a DoHH2 leukemia xenograft mouse model and in healthy mice revealed moderate FLIdU accumulation, followed by a significant washout of activity in proliferating tissues such as splenic and tumor tissues. In contrast, intraperitoneal coinjection with [¹⁸F]FLT showed high uptake and high activity retention up to 2 h, in both splenic and tumor tissues. Uptake in stomach tissues and increasing fractions of [¹³¹I]iodide in urine indicated metabolic instability of [¹³¹I]FLIdU due to rapid deiodination. Therefore, [¹³¹I]FLIdU alone does not seem to be a promising compound, neither for diagnostic imaging nor for potential therapeutic applications

[en] The aim of this study was to determine whether the thymidine analogue 3'-deoxy-3'-[¹⁸F]fluorothymidine ([¹⁸F]FLT) is adequate for early evaluation of the response of malignant lymphoma to antiproliferative treatment in a mouse xenotransplant model. Immunodeficient mice bearing a follicular lymphoma xenotransplant were treated with high-dose chemotherapy (cyclophosphamide, n 10), immunotherapy (CD20 mAb, ibritumomab-tiuxetan, n = 10) or radioimmunotherapy ([⁹⁰Y]CD20 mAb, Zevalin, n = 10). Forty-eight hours after treatment, antiproliferative effects were assessed with [¹⁸F]FLT. Ninety minutes after i.v. injection of 5-10 MBq [¹⁸F]FLT, mice were sacrificed and radioactivity within the tumour and normal organs was measured using a gamma counter and calculated as % ID/g. The proliferation fraction in tissue samples derived from treated and untreated tumours was evaluated by Ki-67 immunohistochemistry, which served as the reference for proliferative activity. In untreated lymphoma, the mean proliferation fraction was 83.6%. After chemotherapy, the mean proliferation fraction decreased to 39.3% (p = 0.0001), after immunotherapy to 77.6% (p = 0.0078) and after radioimmunotherapy to 78.8% (p = 0.014). In none of the animals was a significant change in tumour size observed. In untreated lymphoma, tumoural [¹⁸F]FLT uptake was 5.4% ID/g, after chemotherapy it was 1.5% (p = 0.0005), after immunotherapy, 3.9% (non-significant), and after radioimmunotherapy, 5.8% (non-significant). In a lymphoma xenotransplant model, [¹⁸F]FLT detects early antiproliferative drug activity before changes in tumour size are visible. These findings further support the use of [¹⁸F]FLT-PET for imaging early response to treatment in malignant lymphoma. (orig.)

[en] Several radiolabeled thymidine analogs as metabolic probes of cell proliferation were developed specifically addressing DNA synthesis. Thymidine analogs containing carboranylalkyl groups for neutron capture therapy at the N-3 position were found to be good substrates for cytosolic thymidine kinase 1 (TK1). According to this approach, a DO3A macrocycle in N-3 position was attached to thymidine. The 3-DO3A thymidine analog was labeled with ⁶⁸Ga and ¹¹¹In. Different lipophilicities of the corresponding radiometal-thymidines were detected via RP-HPLC. [¹¹¹In]DO3A-thymidine ([¹¹¹In]D3T) was evaluated for cellular uptake in different cell lines (HL60 and DoHH2). Cellular uptake was low in both cell lines. Phosphorylation of the radioconjugates by TK1 was negligible. Although stable complexation of radiometals to thymidine was obtained, introduction of the macrocycle DO3A reduced the affinity to cytosolic TK1 drastically. Low cellular uptake can be ascribed to missing substrate specificity of [¹¹¹In]DO3A-thymidine for TK1. The absence of substrate specificity may be due to the bulky macrocyclic chelator and partial charges remaining on the coordination sphere due to a more complex solution structure

[en] Highlights: • Optimization of the circumstances of reduction of As(V). • New HPLC method for As(III)/As(V) separation. • Optimization of labelling process between As(III) and dithiol complex agent. - Abstract: The radiochemical separation of n.c.a. arsenic on its own or for radio-labelling purposes usually involves the issue of reducing arsenic(V). Numerous approaches for reducing pentavalent arsenic have been examined. A novel HPLC method has also been presented for accessing the efficiency of the reduction in terms of *As(III)/*As(V). Labelling with trivalent radioarsenic seems to be a promising research field to access new radiopharmaceuticals, for example, using arsenic as a surrogate for phosphorus. Moreover, as a model system, the labelling reaction of *As(III) with dihydrolipoic acid has been systematically optimized.

[en] The aim of the present paper is to review the role of HER2 antibodies, affibodies and nanobodies as vehicles for imaging and therapy approaches in breast cancer, including a detailed look at recent clinical data from antibody drug conjugates and nanobodies as well as affibodies that are currently under development. Clinical and preclinical studies have shown that the use of monoclonal antibodies in molecular imaging is impaired by slow blood clearance, associated with slow and low tumor uptake and with limited tumor penetration potential. Antibody fragments, such as nanobodies, on the other hand, can be radiolabelled with short-lived radioisotopes and provide high-contrast images within a few hours after injection, allowing early diagnosis and reduced radiation exposure of patients. Even in therapy, the small radioactively labeled nanobodies prove to be superior to radioactively labeled monoclonal antibodies due to their higher specificity and their ability to penetrate the tumor. While monoclonal antibodies are well established drug delivery vehicles, the current literature on molecular imaging supports the notion that antibody fragments, such as affibodies or nanobodies, might be superior in this approach.

[en] Kidney fibrosis leads to a progressive reduction in kidney function ultimately resulting in kidney failure. Diagnostic tools to detect kidney fibrosis are all invasive in nature requiring kidney biopsies with subsequent histological validation. In this retrospective study, the diagnostic value of three different radiotracers for the noninvasive prediction of kidney fibrosis was analyzed, taking into account the glomerular filtration rate (GFR) and the intra-renal parenchymal radiotracer uptake. In 81 patients receiving either one of the following molecular imaging probes, [${}^{68}$Ga]Ga-FAPI, [${}^{68}$Ga]Ga-PSMA, or [${}^{68}$Ga]Ga-DOTATOC, kidney function parameters were correlated with SUVmax and SUVmean of the renal parenchyma and background activity measured in lung parenchyma, myocardium, gluteal muscle, and the abdominal aorta. Patients were clustered according to their grade of chronic kidney disease (CKD), and a regression analysis and one-way ANOVA were conducted in this retrospective analysis. We found a negative correlation between GFR and [${}^{68}$Ga]Ga-FAPI uptake for both SUVmax and SUVmean values, whereas background activity showed no correlation with GFR. [${}^{68}$Ga]Ga-DOTATOC and [${}^{68}$Ga]Ga-PSMA did not correlate between CKD stage and intra-renal parenchymal radiotracer uptake. Only [${}^{68}$Ga]Ga-PSMA background activity exhibited a positive correlation with GFR suggesting an unspecific binding/retention potentially due to longer circulation times. There is a significant negative correlation between renal parenchymal [${}^{68}$Ga]Ga-FAPI uptake and GFR, which was not the case for [${}^{68}$Ga]Ga-DOTATOC and [${}^{68}$Ga]Ga-PSMA. This correlation suggests a specific binding of FAPI rather than a potential unspecific retention in the renal parenchyma, underlining the potential value of [${}^{68}$Ga]Ga-FAPI for the noninvasive quantitative evaluation of kidney fibrosis.