Cyclooxygenase-2 (COX-2) is an important biomarker in several tumors. Available imaging probes display relatively low tumor to background ratios (smaller than 2:1). We evaluated newly developed indomethacin (Ind) derivatives for in vivo molecular imaging of COX-2 expressing carcinoma. Radioiodinated Ind derivatives Ind-NH-(CH2)4-NH-3-[I-125]I-Bz ([I-125]5), Ind-NH-(CH2)4-NH-5-[I-124/125]I-Nic ([I-124/125]6) and Ind-NH-(CH2)4-NH-5-[I-125]I-Iphth ([I-125]7) were prepared from the respective SnBu3-precursors (45-80% radiochemical yield; > 95% radiochemical purity). The cellular uptake of [I-125]5 and [I-125]6 correlated with COX-2 expression determined by SDS page/Western blot analysis. [I-125]5 was predominantly localized in the cell membrane while [I-125]6 was internalized and displayed a diffuse and favorable cytoplasmic distribution. In contrast, [I-125]7 showed only low uptake in COX-2 positive cells. Co-incubation with the COX-2 inhibitor Celecoxib led to an almost complete suppression of cellular uptake of [I-125]5 and [I-125]6. In vivo molecular imaging using positron emission tomography (PET) in SCID mice xenografted with COX-2+ (HT29) and COX-2- (HCT116) human colorectal carcinoma cells was performed for [I-124]6. HT29 xenografts displayed a significantly higher uptake than HCT-116 xenografts (5.6 ± 1.5 vs. 0.5 ± 0.1 kBq/g, P < 0.05) with an extraordinary high tumor to muscle ratio (50.3 ± 1.5). Immunohistological staining correlated with the imaging data. In conclusion, the novel radioiodinated indomethacin derivative ([I-124/125]6) could become a valuable tool for development of molecular imaging probes for visualization of COX-2 expressing tumors.
Radionuclide bone scanning (RNB) is considered to be the most practical screening technique for assessing the entire skeleton for skeletal metastases. However, RNB has been shown to be of lower sensitivity than MRI and CT in detecting osteolytic metastases. A prospective study was designed to evaluate the accuracy of planar RNB versus tomographic bone imaging with 18F-labeled NaF and PET (18F PET) in detecting osteolytic and osteoblastic metastases and its dependency on their anatomic localization.Forty-four patients with known prostate, lung or thyroid carcinoma were examined with both planar RNB and 18F PET. A panel of reference methods including MRI of the spine, 1311 scintigraphy, conventional radiography and spiral CT was used as the gold standard. RNB and 18F PET were compared by a lesion-by-lesion analysis using a five-point score for receiver operating characteristic (ROC) curve analysis.18F PET showed 96 metastases (67 of prostate carcinoma and 29 of lung or thyroid cancer), whereas RNB revealed 46 metastases (33 of prostate carcinoma and 13 of lung or thyroid cancer). All lesions found with RNB were also detected with 18F PET. Compared with 18F PET and the reference methods, RNB had a sensitivity of 82.8% in detecting malignant and benign osseous lesions in the skull, thorax and extremities and a sensitivity of 40% in the spine and pelvis. The area under the ROC curve was 0.99 for 18F PET and 0.64 for RNB.18F PET is more sensitive than RNB in detecting osseous lesions. With RNB, sensitivity in detecting osseous metastases is highly dependent on anatomic localization of these lesions, whereas detection rates of osteoblastic and osteolytic metastases are similar. Higher detection rates and more accurate differentiation between benign and malignant lesions with 18F PET suggest the use of 18F PET when possible.
Ziele: In dieser prospektiven Studie wurden Patienten mit Erstdiagnose eines Bronchialkarzinoms oder suspekten pulmonalen Rundherden mit FDG-PET/CT untersucht und die klinische Wertigkeit der fusionierten Bildgebung hinsichtlich Dignitätsbeurteilung und TNM-Staging evaluiert. Methode: Bislang wurden 128 Patienten (Pat.) mit histologisch gesichertem Bronchialkarzinom oder neu diagnostiziertem Lungenrundherd in diese prospektive Studie eingeschlossen. PET/CT wurde bei allen Pat. mit einem modernen Hybrid-Scanner (GE Discovery LS) durchgeführt. 60min nach i.v.-Injektion von 370 MBq F-18-FDG erfolgte zunächst eine Spiral-CT mit Kontrastmittel von cervikal bis inguinal. CT, PET und die PET/CT-Bildfusion wurden für das TNM-Staging verwendet. Als Referenzmethode diente der histologische Befund im resezierten Tumorgewebe bzw. in der Biopsie. Bei Kontraindikation zur Operation wurden sämtliche vorliegenden bildgebenden Verfahren und der klinische Verlauf als Referenz verwendet. Ergebnis: Die Histologie ergab bei 99 Pat. einen malignen Lungentumor. Hinsichtlich der Detektion maligner Tumore ergab sich eine Sensitivität der PET/CT von 99% (98/99), eine Spezifität von 75% (21/28) und eine Treffsicherheit von 94%. Bez. des Lymphknotenstatus wurden 33 Pat. mit PET/CT als negativ beurteilt (N0), 8 Pat. als N1 und 10 Pat. als N2. Für die Differenzierung N0 gegenüber N1/N2 ergab sich eine Sensitivität der PET/CT von 78% (14/18), eine Spezifität von 94% (33/38) und eine Treffsicherheit von 86%. 24 Pat. wurden als inoperabel (N3-Situation) eingestuft, bei 44 Pat. waren zusätzlich hämatogene Fernmetastasen nachweisbar (M1). Die Treffsicherheit der PET/CT zur Unterscheidung operabler (N1, N2, M0) und inoperabler Patienten (N3, M1) beträgt 94% (Sensitivität 91% (50/55), Spezifität 100% (44/44)). Schlussfolgerung: Die fusionierte Bildgebung mit PET/CT ermöglicht eine hohe Treffsicherheit für die Dignitätsbeurteilung suspekter Lungenrundherde und für die Differenzierung operabler (N0, N1, N2) und inoperabler Patienten (N3, M1).
The β+-emitting radionuclide 86gY (t1/2 = 14.7 h) forms a matched-pair with the β--emitting therapeutic radionuclide 90Y (t1/2 = 2.7 d) for theranostic application in medicine. This approach demands a precise knowledge of the positron emission probability of the PET nuclide which was until recently rather uncertain for 86gY. In this work, an 86gY source of high radionuclidic purity was prepared and a direct measurement of the positron emission intensity per 100 decay of the parent (hereafter "positron emission intensity") was performed using high-resolution HPGe detector γ-ray spectroscopy. The electron capture intensity was also determined as an additional check by measuring the Kα and Kβ X-rays of energies 14.1 and 15.8 keV, respectively, using a low energy HPGe detector. From those measurements, normalized values of 27.2 ± 2.0% for β+-emission and 72.8 ± 2.0% for EC were obtained. These results are in excellent agreement with values recently reported in the literature based on a detailed decay scheme study.
Ziel/Aim Integrated histomolecular diagnostics of gliomas according to the World Health Organization (WHO) classification of 2016 has refined diagnostic accuracy and prediction of prognosis. This study aimed at exploring the prognostic value of dynamic O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in newly diagnosed, histomolecularly classified astrocytic gliomas of WHO grades III or IV.
Ziel/Aim One of the core components of emotional processing is the processing of emotional valence which has been studied thoroughly using fMRI. More recently, in order to elucidate the relationship to neurotransmitters, GABA levels were measured using proton magnetic resonance spectroscopy (1H-MRS). So far only few studies addressed the relationship of GABAA-receptor availability with fMRI BOLD signal. In this study we investigated for the first time this relationship during different types of emotional valence processing. We hypothesised a correlation between the BOLD signal and the binding potential of a GABAA receptor ligand in the medial prefrontal cortex.
