[en] The novel thiol-group-selective bifunctional ¹⁸F-labeling agent N-[6-(4-[¹⁸F]fluoro-benzylidene)aminooxyhexyl]maleimide ([¹⁸F]FBAM) has been developed. The bifunctional labeling precursor N-(6-aminoxyhexyl)maleimide containing a thiol-reactive maleimide group and a carbonyl-group-reactive aminooxy group was prepared in only three steps in a total chemical yield of 59%. Subsequent radiolabeling with 4-[¹⁸F]fluorobenzaldehyde gave the bifunctional ¹⁸F-labeling agent [¹⁸F]FBAM in a radiochemical yield of 29%. In a typical experiment, 3.88 GBq of [¹⁸F]fluoride could be converted into 723 MBq of [¹⁸F]FBAM within 69 min. Conjugation of [¹⁸F]FBAM with thiol groups was exemplified with the cystein-containing tripeptide glutathione and with various apolipoproteins of human low-density lipoprotein (LDL) subfractions. The latter was evaluated with respect to the uptake of [¹⁸F]FBAM-LDL subfractions in human hepatoma cells (HepG2) in vitro. In vivo biodistribution studies in rats revealed high stability for [¹⁸F]FBAM-LDL subfractions. Moreover, the metabolic fate of [¹⁸F]FBAM-LDL subfractions in vivo was delineated by dynamic positron emission tomography studies using a dedicated small animal tomograph. Data were compared to former studies that used the NH₂-reactive ¹⁸F-labeling agent N-succinimidyl-4-[¹⁸F]fluorobenzoate. The compound [¹⁸F]FBAM can be considered as an excellent prosthetic group for the selective and mild ¹⁸F labeling of thiol-group-containing biomolecules suitable for subsequent investigations in vitro and in vivo

[en] Three methods for ¹⁸F-labeling of dimeric and tetrameric neurotensin(8-13) derivatives were evaluated with respect to the labeling yield and the required peptide amounts. Labeling using N-succinimidyl-4-[¹⁸F]fluorobenzoate ([¹⁸F]SFB) gave low radiochemical yield for the dimeric peptides. Coupling of the tetramer with [¹⁸F]SFB was not successful. High yields were obtained for labeling of the aminooxy-functionalized neurotensin(8-13) dimer using 4-[¹⁸F]fluorobenzaldehyde ([¹⁸F]FBA) whilst coupling of the corresponding tetramer gave only low yields. Labeling of sulfydryl-functionalized neurotensin(8-13) derivatives using the maleinimide 4-[¹⁸F]fluorobenzaldehyde-O-[6-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-hexyl] -oxime ([¹⁸F]FBAM) resulted in high radiochemical yields for both, the dimer and the tetramer. Therefore, [¹⁸F]FBAM seems to be the most suitable ¹⁸F-labeling agent for multivalent neurotensin(8-13) derivatives

[en] Radiochemical conversion is an important term to be included in the “Consensus nomenclature rules for radiopharmaceutical chemistry”. Radiochemical conversion should be used to define reaction efficiency by measuring the transformation of components in a crude reaction mixture at a given time, whereas radiochemical yield is better suited to define the efficiency of an entire reaction process including, for example, separation, isolation, filtration, and formulation.

[en] The bombesin derivative RM2 is a GRPr antagonist with strong binding affinity to prostate cancer (PCa). In this study, the impact of [${}^{68}$Ga]Ga-RM2 positron emission tomography-computed tomography (PET-CT) for the detection of primary PCa was compared with that of [${}^{18}$F]FCH PET-CT and multiparametric magnetic resonance imaging (mpMRI). This phase I/II study was conducted in 30 biopsy-positive PCa subjects. The patients were stratified into high (10 patients), intermediate (10 patients), and low risk (10 patients) for extraglandular metastases as defined by National Comprehensive Cancer Network (NCCN) criteria (NCCN Clinical Practice Guidelines in Oncology,). The prostate gland was classified in 12 anatomic segments for data analysis of the imaging modalities as well as histopathologic findings. The segment with the highest radiotracer uptake was defined as the "index lesion." All cases were scheduled to undergo prostatectomy with pelvic lymph node (LN) dissection in intermediate- and high-risk patients. Intraprostatic and pelvic nodal [${}^{68}$Ga]Ga-RM2 and [${}^{18}$F]FCH PET-CT findings were correlated with mpMRI and histopathologic results. Of the 312 analyzed regions, 120 regions (4 to 8 lesions per patient) showed abnormal findings in the prostate gland. In a region-based analysis, overall sensitivity and specificity of [${}^{68}$Ga]Ga-RM2 PET-CT in the detection of primary tumor were 74% and 90%, respectively, while it was 60% and 80% for [${}^{18}$F]FCH PET-CT and 72% and 89% for mpMRI. Although the overall sensitivity of [${}^{68}$Ga]Ga-RM2 PET-CT was higher compared to that of [${}^{18}$F]FCH PET-CT and mpMRI, the statistical analysis showed only significant difference between [${}^{68}$Ga]Ga-RM2 PET-CT and [${}^{18}$F]FCH PET-CT in the intermediate-risk group (p = 0.01) and [${}^{68}$Ga]Ga-RM2 PET-CT and mpMRT in the high-risk group (p = 0.03). In the lesion-based analysis, there was no significant difference between SUVmax of [${}^{68}$Ga]Ga-RM2 and [${}^{18}$F]FCH PET-CT in the intraprostatic malignant lesions ([${}^{68}$Ga]Ga-RM2: mean SUVmax: 5.98 ± 4.13, median: 4.75; [${}^{18}$F]FCH: mean SUVmax: 6.08 ± 2.74, median: 5.5; p = 0.13). [${}^{68}$Ga]Ga-RM2 showed promising PET tracer for the detection of intraprostatic PCa in a cohort of patients with different risk stratifications. However, significant differences were only found between [${}^{68}$Ga]Ga-RM2 PET-CT and [${}^{18}$F]FCH PET-CT in the intermediate-risk group and [${}^{68}$Ga]Ga-RM2 PET-CT and mpMRT in the high-risk group. In addition, GRP-R-based imaging seems to play a complementary role to choline-based imaging for full characterization of PCa extent and biopsy guidance in low- and intermediate-metastatic-risk PCa patients and has the potential to discriminate them from those at higher risks. [${}^{68}$Ga]Ga-RM2 is a promising PET tracer with a high detection rate for intraprostatic PCa especially in intermediate-risk prostate cancer patients. GRPr-based imaging seems to play a complementary role to choline-based or PSMA-based PET/CT imaging in selected low- and intermediate-risk PCa patients for better characterization and eventually biopsy guidance of prostate cancer disease.

[en] Purpose: Amyloid-β (Aβ) plaques are a major pathological hallmark of Alzheimer's disease (AD). The noninvasive detection of Aβ plaques may increase the accuracy of clinical diagnosis as well as monitor therapeutic interventions. While [¹¹C]-PiB is the most widely used Aβ positron emission tomography (PET) radiotracer, due to the short half-life of ¹¹C (20 min), its application is limited to centers with an on-site cyclotron and ¹¹C radiochemistry expertise. Therefore, novel [¹⁸F] (half-life 110 min)-labeled Aβ PET tracers have been developed. We have demonstrated that [¹⁸F]-florbetaben-PET can differentiate individuals diagnosed with AD from healthy elderly, Parkinson's disease and frontotemporal lobe dementia (FTLD-tau) patients. While [¹⁸F]-florbetaben-PET retention matched the reported postmortem distribution of Aβ plaques, the nature of [¹⁸F]-florbetaben binding to other pathological lesions comprising misfolded proteins needs further assessment. The objective of this study was to determine whether Florbetaben selectively binds to Aβ plaques in postmortem tissue specimens containing mixed pathological hallmarks (i.e., tau and α-synuclein aggregates). Method: Human AD, FTLD-tau and dementia with Lewy bodies (DLB) brain sections were analyzed by [¹⁸F]-florbetaben autoradiography and [³H]-florbetaben high-resolution emulsion autoradiography and [¹⁹F]-florbetaben fluorescence microscopy. Results: Both autoradiographical analyses demonstrated that Florbetaben exclusively bound Aβ plaques in AD brain sections at low nanomolar concentrations. Furthermore, at concentrations thousand-folds higher than those during a PET scan, [¹⁹F]-florbetaben did not bind to α-synuclein or tau aggregates in DLB and FTLD-tau brain sections, respectively. Detection of [¹⁹F]-florbetaben staining by fluorescence microscopy in several AD brain regions demonstrated that Florbetaben identified Aβ plaques in all brain regions examined. Conclusion: This study provides further evidence that [¹⁸F]-florbetaben-PET is a highly selective radiotracer to assess Aβ plaque deposition in the brain.