[What actually happens in hybrid imaging?] / Was passiert eigentlich in der Hybridbildgebung?

CLINICAL/METHODOLOGICAL ISSUE: The goal of this article is to shed light on innovations in perfusion imaging and the fields of application that have opened up in hybrid imaging of the heart. STANDARD RADIOLOGICAL METHODS: As before, the most commonly used modalities in hybrid imaging are single photon emission computed tomography (SPECT) and positron emission tomography/computed tomography (PET/CT). Perfusion tracers and the radioactively labeled glucose analog 18F­fluorodeoxyglucose (FDG) are commonly used for vitality imaging. METHODICAL INNOVATIONS: Use of PET/MRI (magnetic resonance imaging) is becoming increasingly widespread. In addition, FDG is also increasingly applied in imaging infectious and inflammatory myocardial diseases. Furthermore, novel tracers are used, such as the amyloid-specific tracers in cardiac amyloidosis. PERFORMANCE: Overall, this development has led to an increasing use of hybrid imaging techniques. These still include myocardial perfusion imaging, but are also used in inflammatory and infectious diseases such as endocarditis, myocarditis and sarcoidosis, as well as in underestimated diseases such as cardiac amyloidosis. The use of tracers has led to the creation of new fields of application in hybrid imaging. PRACTICAL RECOMMENDATIONS: Hybrid imaging combining myocardial perfusion and coronary visualization seems to be particularly advantageous in complex cases such as multivessel disease. In infectious and inflammatory myocardial diseases, FDG PET/CT or PET/MRI has clearly demonstrated its added value. New fields of application are very promising, but their significance has yet to be clearly demonstrated.

[Nuclear medicine procedure guideline for sentinel lymph node localization]. / DGN-Handlungsempfehlung (S1-Leitlinie) ­ Version 3.

The authors present a procedure guideline for scintigraphic detection of sentinel lymph nodes in malignant melanoma, in breast cancer, in penile and vulva tumors, in head and neck cancer, and in prostate carcinoma. Important goals of sentinel lymph node scintigraphy comprise reduction of the extent of surgery, lower postoperative morbidity and optimization of histopathological examination focussing on relevant lymph nodes. Sentinel lymph node scintigraphy itself does not diagnose tumorous lymph node involvement and is not indicated when lymph node or distant metastases have been definitely diagnosed before sentinel lymph node scintigraphy. Procedures are compiled with the aim to reliably localise sentinel lymph nodes with a high detection rate typically in early tumour stages. New aspects in this guideline are new radiopharmaceuticals such as tilmanocept and Tc-99m-PSMA and SPECT/CT allowing an easier anatomical orientation. Initial dynamic lymphoscintigraphy in breast cancer is of little significance nowadays. Radiation exposure is low so that pregnancy is not a contraindication for sentinel lymph node scintigraphy. A one-day protocol should preferentially be used. Even with high volumes of scintigraphic sentinel lymph node procedures surgeons, theatre staff and pathologists receive a radiation exposure < 1 mSv/year so that they do not require occupational radiation surveillance. Aspects of quality control were included (scintigraphy, quality control of gamma probe, 6 h SLN course for surgeons, certified breast centers, medical surveillance center).

Role of choline PET/CT in guiding target volume delineation for irradiation of prostate cancer.

Choline PET/CT has shown limitations for the detection of primary prostate cancer and nodal metastatic disease, mainly due to limited sensitivity and specificity. Conversely in the restaging of prostate cancer recurrence, choline PET/CT is a promising imaging modality for the detection of local regional and nodal recurrence with an impact on therapy management. This review highlights current literature on choline PET/CT for radiation treatment planning in primary and recurrent prostate cancer. Due to limited sensitivity and specificity in differentiating between benign and malignant prostatic tissues in primary prostate cancer, there is little enthusiasm for target volume delineation based on choline PET/CT. Irradiation planning for the treatment of single lymph node metastases on the basis of choline PET/CT is controversial due to its limited lesion-based sensitivity in primary nodal staging. In high-risk prostate cancer, choline PET/CT might diagnose lymph node metastases, which potentially can be included in the conventional irradiation field. Prior to radiation treatment of recurrent prostate cancer, choline PET/CT may prove useful for patient stratification by excluding distant disease which would require systemic therapy. In patients with local recurrence, choline PET/CT can be used to delineate local sites of recurrence within the prostatic resection bed allowing a boost to PET-positive sites. In patients with lymph node metastases outside the prostatic fossa and regional metastatic lymph nodes, choline PET/CT might influence radiation treatment planning by enabling extension of the target volume to lymphatic drainage sites with or without a boost to PET-positive lymph nodes. Further clinical randomized trials are required to assess treatment outcomes following choline-based biological radiation treatment planning in comparison with conventional radiation treatment planning.

[German guidelines for brain tumour imaging by PET and SPECT using labelled amino acids]. / PET- und SPECT-Untersuchungen von Hirntumoren mit radioaktiv markierten Aminosäuren.

For the primary diagnosis of brain tumours, morphological imaging by means of magnetic resonance imaging (MRI) is the current method of choice. The complementary use of functional imaging by positron emitting tomography (PET) and single photon emitting computerized tomography (SPECT) with labelled amino acids can provide significant information on some clinically relevant questions, which are beyond the capacity of MRI. These diagnostic issues affect in particular the improvement of biopsy targeting and tumour delineation for surgery and radiotherapy planning. In addition, amino acid labelled PET and SPECT tracers are helpful for the differentiation between tumour recurrence and non-specific post-therapeutic tissue changes, in predicting prognosis of low grade gliomas, and for metabolic monitoring of treatment response. The application of dynamic PET examination protocols for the assessment of amino acid kinetics has been shown to enable an improved non-invasive tumour grading. The purpose of this guideline is to provide practical assistance for indication, examination procedure and image analysis of brain PET/SPECT with labelled amino acids in order to allow for a high quality standard of the method. After a short introduction on pathobiochemistry and radiopharmacy of amino acid labelled tracers, concrete and detailed information is given on the several indications, patient preparation and examination protocols as well as on data reconstruction, visual and quantitative image analysis and interpretation. In addition, possible pitfalls are described, and the relevant original publications are listed for further information.

New trends for staging and therapy for localized gastroesophageal cancer: the role of PET.

Treatment options for localized gastroesophageal cancers reach from limited resection to multimodality treatment. Accurate clinical assessment, prognostic and predictive information are needed to select the most appropriate treatment approach. Positron emission tomography (PET) in combination with computed tomography (CT) in a hybrid imaging modality PET-CT may refine the staging accuracy and add prognostic information. Moreover, experiences from diverse centers indicate that PET also might improve significantly the assessment of response to preoperative chemotherapy and chemoradiotherapy. This article outlines the current value of PET in the staging and multidisciplinary care of gastroesophageal cancer. At this stage, it remains unclear whether the prognosis of patients can be improved by implementing PET in the management of localized disease. Prospective multicenter studies have to be carried out to validate metabolic cut-off values and to prove the benefit of PET-guided treatment decisions.

[Tracers in oncology - preclinical and clinical evaluation]. / Innovative Tracer in der onkologischen Diagnostik. Präklinische und klinische Evaluierung.

UNLABELLED: In oncology, PET and PET/CT with tracers beyond FDG target more specific biological processes, such as proliferation (18F-3´-fluoro-3´-deoxy-L-thymidine; 18F-FLT), tumour hypoxia (18F-fluoromisonidazol; 18F-FMISO) and phospholipid metabolism (radioactively labelled choline derivates). FLT is a thymidine analogue which can be labelled with 18F. PET with 18F-FLT enables to non-invasively image and to quantify the proliferation fraction of tumours. Proliferation dependent accumulation of FLT has been demonstrated for a variety of solid and haematologic neoplasms including lung cancer, breast cancer, gastric cancer, colorectal cancer and malignant lymphoma. Furthermore, FLT has been suggested as surrogate marker for the assessment of response to treatment, especially when targeted drugs are utilized. PET imaging in particular has emerged as a promising non-invasive tool to accurately characterize tumour oxygenation. The great promise of PET/CT is its potential as a single imaging modality for whole body staging that provides anatomical and biological information on the disease as a whole. It allows a more precise estimation of the hypoxic tumour volume as well as comparisons on a voxel-by-voxel basis (parametric mapping). PET and PET/CT with hypoxia tracers thus offer the potential to optimize and individualize therapy for patients suffering from cancer. PET- and PET/CT-studies using 11C- or 18F-labeled choline derivates recently have shown promising results for re-staging prostate cancer in patients with biochemical recurrence and advanced prostate cancer. In patients with biochemical recurrence of prostate cancer after primary therapy the detection rate of 11C-choline-PET/CT shows a positive relationship with serum PSA-levels. In these patients 11C-choline PET/CT allows not only to diagnose but also to localize recurrent disease with implications on disease management (localised vs. systemic therapy). CONCLUSION: The clinical success of multimodal imaging with PET/CT is expected to promote the combination of MRI and PET in the future.

[Bone scanning with sodium 18F-fluoride PET and PET/CT. German guideline Version 1.0.]. / Skelettdiagnostik mittels 18F-Natriumfluorid-PET und -PET/CT. DGN-Leitlinie Version 1.0.

In nuclear medicine, bone scanning is based on the principle of scintigraphy using bone-seeking radiopharmaceuticals which accumulate in sites of increased bone formation. From a historical point of view, (18)F-fluoride was one of the first osteotropic tracers which was replaced by (99m)Tc-labelled polyphosphonates. With the development of modern PET equipment the superior diagnostic performance of (18)F-fluoride PET for the detection and characterization of osseous lesions was proven in comparison to conventional bone scanning. Recently, its importance as a substitute of conventional skeletal scintigraphy increased in a time with limited availability of (99)Mo/(99m)Tc. To ensure health care during this period, (18)F-fluoride PET currently became part of common outpatient care. This guideline comprehends recommendations on indications, protocols, interpretation and reporting of (18)F-fluoride PET and PET/CT.

Lesion concordance, image quality and artefacts in PET/CT: results of a multicenter study.

AIM: This study had three major objectives: 1.) to record the number of concordant (both in PET and CT) pathological lesions in different body regions/organs, 2.) to evaluate the image quality and 3.) to determine both, the quantity and the quality of artefacts in whole body FDG PET/CT scans. PATIENTS, METHODS: Routine whole body scans of 353 patients referred to FDG-PET/CT exams at 4 university hospitals were employed. All potentially malignant lesions in 13 different body regions/organs were classified as either concordant or suspicious in FDG-PET or CT only. In the latter case the diagnostic relevance of this disparity was judged. The image quality in PET and CT was rated as a whole and separately in 5 different body regions. Furthermore we investigated the frequency and site of artefacts caused by metal implants and oral or intravenous contrast media as well as the subjective co-registration quality (in 4 body regions) and the diagnostic impact of such artefacts or misalignment. In addition, the readers rated the diagnostic gain of adding the information from the other tomographic method. RESULTS: In total 1941 lesions (5.5 per patient) were identified, 1094 (56%) out of which were concordant. 602 (71%) out of the 847 remaining lesions were detected only with CT, 245 (29%) were only PET-positive. As expected, CT particularly depicted the majority of lesions in the lungs and abdominal organs. However, the diagnostic relevance was greater with PET-only positive lesions. Most of the PET/CT scans were performed with full diagnostic CT including administration of oral and intravenous contrast media (> 80%). The image quality in PET and CT was rated excellent. Artefacts occurred in more than 60% of the scans and were mainly due to (dental) metal implants and contrast agent. Nevertheless there was almost no impact on diagnostic confidence if reading of the non attenuation corrected PET was included. The co-registration quality in general was also rated as excellent. Misalignment mostly occurred due to patient motion and breathing and led to diagnostic challenges in about 4% of all exams. The diagnostic gain of adding PET to a CT investigation was rated higher than vice versa. CONCLUSIONS: As the image quality in both PET and CT was more than satisfying, CT-artefacts almost never led to diagnostic uncertainties and serious misalignment rarely occurred, PET/CT can be considered as suitable for routine use and may replace single PET- and CT-scans. However, additional reading of the non attenuation corrected PET is mandatory to assure best possible diagnostic confidence in PET. Since approximately half of all lesions found in PET/CT were not concordant, at least in a setting with a diagnostic CT the exams need to be reported by both a nuclear medicine physician and a radiologist in consensus.

[PSMA-based theranostics for prostate cancer : From imaging to treatment]. / PSMA-basierte Theranostik beim Prostatakarzinom : Von der Bildgebung zur Therapie.

BACKGROUND: In recent years nuclear medicine theranostics using radiolabeled prostate-specific membrane antigen (PSMA) ligands have gained increasing importance in the management of prostate cancer. AIM: The aim of this work is to highlight the value of theranostic concepts using radiolabeled PSMA ligands for both the diagnostic work-up and treatment of advanced prostate cancer. MATERIAL AND METHODS: The currently available knowledge in the literature is summarized and presented. RESULTS: The use of PSMA in positron emission tomography-computed tomography (PET/CT) shows a high sensitivity and specificity for prostate cancer imaging, particularly in patients with biochemical recurrences. Furthermore, promising results are also reported for staging of primary prostate cancer and treatment monitoring. In addition, radioligand therapy using alpha and beta emitters is a promising third line treatment option in intensively pretreated patients with metastases. The reduction of side effects and optimization of the treatment sequence of radioligand therapy is of increasing importance. CONCLUSION: Nuclear medicine theranostics have an increasing clinical impact on the diagnostics and treatment of prostate cancer.

[18F]-florbetaben PET/CT Imaging in the Alzheimer's Disease Mouse Model APPswe/PS1dE9.

BACKGROUND: Positron-emission-tomography (PET) using 18F labeled florbetaben allows noninvasive in vivo-assessment of amyloid-beta (Aß), a pathological hallmark of Alzheimer's disease (AD). In preclinical research, [18F]-florbetaben-PET has already been used to test the amyloid-lowering potential of new drugs, both in humans and in transgenic models of cerebral amyloidosis. The aim of this study was to characterize the spatial pattern of cerebral uptake of [18F]-florbetaben in the APPswe/ PS1dE9 mouse model of AD in comparison to histologically determined number and size of cerebral Aß plaques. METHODS: Both, APPswe/PS1dE9 and wild type mice at an age of 12 months were investigated by smallanimal PET/CT after intravenous injection of [18F]-florbetaben. High-resolution magnetic resonance imaging data were used for quantification of the PET data by volume of interest analysis. The standardized uptake values (SUVs) of [18F]-florbetaben in vivo as well as post mortem cerebral Aß plaque load in cortex, hippocampus and cerebellum were analyzed. RESULTS: Visual inspection and SUVs revealed an increased cerebral uptake of [18F]-florbetaben in APPswe/ PS1dE9 mice compared with wild type mice especially in the cortex, the hippocampus and the cerebellum. However, SUV ratios (SUVRs) relative to cerebellum revealed only significant differences in the hippocampus between the APPswe/PS1dE9 and wild type mice but not in cortex; this differential effect may reflect the lower plaque area in the cortex than in the hippocampus as found in the histological analysis. CONCLUSION: The findings suggest that histopathological characteristics of Aß plaque size and spatial distribution can be depicted in vivo using [18F]-florbetaben in the APPswe/PS1dE9 mouse model.

The detection rate of [11C]choline-PET/CT depends on the serum PSA-value in patients with biochemical recurrence of prostate cancer.

PURPOSE: An increase of the serum PSA-level is a sensitive in vitro marker for recurrent prostate cancer. However, it remains difficult to differentiate between local, regional or distant recurrent disease. The aim of this study was to assess the relationship between the detection rate of [(11)C]Choline-PET/CT and the serum PSA-level in patients with a biochemical recurrence of prostate cancer with the view towards localisation of recurrent disease. METHODS: Sixty-three patients (mean age, 68.8 +/- 6.9; range, 45-83 years) with biochemical recurrence after primary therapy for prostate cancer were included in the analysis. Mean PSA-levels were 5.9 +/- 9.7 ng/ml (range, 0.2-39 ng/ml; median, 2.15). Of the 63 patients, 17 were under anti-androgen therapy at the time of [(11)C]Choline PET/CT. Patients underwent a [(11)C]Choline-PET/CT study after injection of 656 +/- 119 MBq [(11)C]Choline on a Sensation 16 Biograph PET/CT scanner. RESULTS: Of the 63 patients, 35 (56%) showed a pathological [(11)C]Choline uptake. The detection rate of [(11)C]Choline-PET/CT showed a relationship with the serum PSA-level: The detection rate was 36% for a PSA-value <1 ng/ml, 43% for a PSA-value 1-<2 ng/ml, 62% for a PSA-value 2-<3 ng/ml and 73% for a PSA-value >or=3 ng/ml. Anti-androgen therapy did not show a significant effect on the detection rate of [(11)C]Choline-PET/CT (p = 0.374). CONCLUSION: As an important result our study shows that even for PSA-values <1.0 ng/ml the detection efficiency of [(11)C]Choline-PET/CT is 36%. Furthermore, the detection rate of [(11)C]Choline-PET/CT shows a positive relationship with serum PSA-levels in patients with biochemical recurrence of prostate cancer after primary therapy. Therefore, in these patients, [(11)C]Choline PET/CT allows not only to diagnose but also to localise recurrent disease with implications on disease management (localised vs systemic therapy).

External radiation exposure, excretion, and effective half-life in 177Lu-PSMA-targeted therapies.

BACKGROUND: Prostate-specific membrane antigen (PSMA)-targeted therapy with 177Lu-PSMA-617 is a therapeutic option for patients with metastatic castration-resistant prostate cancer (mCRPC). To optimize the therapy procedure, it is necessary to determine relevant parameters to define radiation protection and safety necessities. Therefore, this study aimed at estimating the ambient radiation exposure received by the patient. Moreover, the excreted activity was quantified. RESULTS: In total, 50 patients with mCRPC and treated with 177Lu-PSMA-617 (mean administered activity 6.3 ± 0.5 GBq) were retrospectively included in a bi-centric study. Whole-body dose rates were measured at a distance of 2 m at various time points after application of 177Lu-PSMA-617, and effective half-lives for different time points were calculated and compared. Radiation exposure to the public was approximated using the dose integral. For the estimation of the excreted activity, whole body measurements of 25 patients were performed at 7 time points. Unbound 177Lu-PSMA-617 was rapidly cleared from the body. After 4 h, approximately 50% and, after 12 h, approximately 70% of the administered activity were excreted, primarily via urine. The mean dose rates were the following: 3.6 ± 0.7 µSv/h at 2 h p. i., 1.6 ± 0.6 µSv/h at 24 h, 1.1 ± 0.5 µSv/h at 48 h, and 0.7 ± 0.4 µSv/h at 72 h. The mean effective half-life of the cohort was 40.5 ± 9.6 h (min 21.7 h; max 85.7 h). The maximum dose to individual members of the public per treatment cycle was ~ 250 ± 55 µSv when the patient was discharged from the clinic after 48 h and ~ 190 ± 36 µSv when the patient was discharged after 72 h. CONCLUSIONS: In terms of the radiation exposure to the public, 177Lu-PSMA is a safe option of radionuclide therapy. As usually four (sometimes more) cycles of the therapy are performed, it must be conducted in a way that ensures that applicable legal requirements can be followed. In other words, the radiation exposure to the public and the concentration of activity in wastewater must be sub-marginal. Therefore, in certain countries, hospitalization of these patients is mandatory.

Decitabine demonstrates antileukemic activity in B cell precursor acute lymphoblastic leukemia with MLL rearrangements.

BACKGROUND: Promotor hypermethylation of CpG islands is common in B cell precursor acute lymphoblastic leukemia (BCP-ALL) with mixed lineage leukemia (MLL) gene rearrangements. Hypomethylating agents (HMA) such as azacitidine (AZA) and decitabine (DEC) reduce DNA hypermethylation by incorporation into DNA and were successfully introduced into the clinic for the treatment of myeloid neoplasias. METHODS: Here, we investigated whether HMA induce comparable biological effects in MLL-positive BCP-ALL. Further, efficacy of HMA and concomitant application of cytostatic drugs (cytarabine and doxorubicin) were evaluated on established SEM and RS4;11 cell lines. In addition, promising approaches were studied on BCP-ALL cell line- and patient-derived xenograft models. RESULTS: In general, DEC effects were stronger compared to AZA on MLL-positive BCP-ALL cells. DEC significantly reduced proliferation by induction of cell cycle arrest in G0/G1 phase and apoptosis. Most sensitive to HMA were SEM cells which are characterized by a fast cell doubling time. The combination of low-dose HMA and conventional cytostatic agents revealed a heterogeneous response pattern. The strongest antiproliferative effects were observed when ALL cells were simultaneously exposed to HMA and cytostatic drugs. Most potent synergistic effects of HMA were induced with cytarabine. Finally, the therapeutic potential of DEC was evaluated on BCP-ALL xenograft models. DEC significantly delayed leukemic proliferation in xenograft models as demonstrated longitudinally by non-invasive bioluminescence as well as 18F-FDG-PET/CT imaging. Unexpectedly, in vivo concomitant application of DEC and cytarabine did not enhance the antiproliferative effect compared to DEC monotherapy. CONCLUSIONS: Our data reveal that DEC is active in MLL-positive BCP-ALL and warrant clinical evaluation.

[Somatostatin receptor PET/CT (SSTR-PET/CT)]. / Somatostatinrezeptor-PET/CT.

The present guideline is focused on quality assurance of somatostatin receptor PET/CT (SSTR-PET/CT) in oncology patients. The document has been developed by a multidisciplinary board of specialists providing consensus of definitions, prerequisites, methodology, operating procedures, assessment, and standardized reporting. In particular, imaging procedures for the two most commonly used radioligands of human SSTR, i. e. 68Ga-DOTATOC and 68Ga-DOTATATE are presented. Overall, SSTR-PET/CT requires close interdisciplinary communication and cooperation of referring and executing medical disciplines, taking into account existing guidelines and recommendations of the European and German medical societies, including the European Association of Nuclear Medicine (EANM), German Society for Endocrinology (DGE), German Society for Nuclear Medicine (DGN) and German Society for Radiology (DRG).

Influence of PET/CT-introduction on PET scanning frequency and indications. Results of a multicenter study.

AIM: To evaluate the influence of the introduction of combined PET/CT scanners into clinical routine. This investigation addresses the quantitative changes between PET/CT and stand alone PET. METHODS: The study included all examinations performed on stand alone PET- or PET/CT-scanners within 12 month prior to and after implementation of PET/CT. The final data analysis included five university hospitals and a total number of 15 497 exams. We distinguished exams on stand alone tomographs prior to and after installation of the combined device as well as PET/CT scans particularly with regard to disease entities. Various further parameters were investigated. RESULTS: The overall number of PET scans (PET and PET/CT) rose by 146% while the number of scans performed on stand alone scanners declined by 22%. Only one site registered an increase in stand alone PET. The number of exams for staging in oncology increased by 196% while that of cardiac scans decreased by 35% and the number of scans in neurology rose by 47%. The use of scans for radiotherapy planning increased to 7% of all PET/CT studies. The increase of procedures for so-called classic PET oncology indications was moderate compared to the more common tumors. An even greater increase was observed in some rare entities. CONCLUSIONS: The introduction of PET/CT led to more than a doubling of overall PET procedures with a main focus on oncology. Some of the observed changes in scanning frequency may be caused by a rising availability of new radiotracers and advancements of competing imaging methods. Nevertheless the evident increase in the use of PET/CT for the most common tumour types demonstrates its expanding role in cancer staging. The combination of molecular and morphologic imaging has not only found its place but is still gaining greater importance with new developments in technology and radiochemistry.

Cerebral haemodynamics during hypo- and hypercapnia: determination with simultaneous 15O-butanol-PET and transcranial Doppler sonography.

AIM: Transcranial Doppler sonography (TCD) is increasingly used in cerebrovascular disease for monitoring brain perfusion. It allows estimation of cerebral blood flow (CBF) by the measurement of cerebral blood flow velocity (CBFV). The CBFV as well as CBF are intimately associated with the intravascular CO2-concentration. Thus, hyper- or hypocapnia can be used to induce a defined range of blood flows. The aim of our study was the comparison of vasomotor reactivity assessed with simultaneous TCD and quantitative regional CBF-measurements (rCBF) by PET (serving as the reference method for in-vivo quantification of rCBF). PATIENTS, METHODS: Six healthy young volunteers participated in this study. CBF was measured using 15O-butanol PET. A flow and dispersion-model was fitted to the measured time activity curves using arterial input curves. Each subject underwent five scans at five different end-tidal CO2 levels (EtCO2): 25, 32, 40, 48, and 55 mmHg. CBFV was assessed by continuous bilateral TCD of the middle cerebral artery (MCA). Volumes of interest for rCBF determination were placed in grey matter of the prefrontal cortex (PFC) as determined from individual MRIs. Comparisons between the rCBF, EtCO2 and CBFV were carried out with regression and correlation analysis and paired t-tests. RESULTS: Strong positive linear correlations of rCBF and CBFV with the CO2-concentration and linear relationships between rCBF and CBFV were found in each individual. Normalised CO2-reactivities measured by TCD and PET were closely correlated. CONCLUSIONS: TCD-measurements of vascular reactivity in healthy volunteers show a high correlation to those acquired with PET that serves as the reference method of quantitative rCBF-measurement. The results of the MCA insonation are a close approximation of the rCBF changes induced by variations of EtCO2.

[FDG-PET/CT in oncology. German Guideline]. / FDG-PET/CT in der Onkologie. Leitlinie.

FDG-PET/CT examinations combine metabolic and morphologic imaging within an integrated procedure. Over the past decade PET/CT imaging has gained wide clinical acceptance in the field of oncology. This FDG-PET/CT guideline focuses on indications, data acquisition and processing as well as documentation of FDG-PET/CT examinations in oncologic patients within a clinical and social context specific to Germany. Background information and definitions are followed by examples of clinical and research applications of FDG-PET/CT. Furthermore, protocols for CT scanning (low dose and contrast-enhanced CT) and PET emission imaging are discussed. Documentation and reporting of examinations are specified. Image interpretation criteria and sources of errors are discussed. Quality control for FDG and PET/CT-systems, qualification requirements of personnel as well as legal aspects are presented.

Patients with in-stent restenoses: comparison of intracoronary beta-brachytherapy using a rhenium-188 filled balloon catheter with the polymer-based paclitaxel-eluting taxus-express stent.

AIMS: We compared the intracoronary beta-brachytherapy using a liquid rhenium-188 filled balloon with the slow-release, polymer-based, paclitaxel-eluting Taxus-Express stent for treatment of in-stent restenoses. PATIENTS, METHODS: During the same study period, patients with restenoses in bare-metal stents were either treated with Taxus-Express stents (n = 50) or beta-brachytherapy after successful angioplasty (n = 51). For brachytherapy 30 Gy in 0.5 mm tissue depth were administered. The irradiated segment exceeded the traumatized segment 7.5 mm on both sides. Primary endpoint was the minimal lumen diameter (MLD) at the target lesion at six months follow-up. Angiographic follow-up was available in 78% (n = 79/101) and clinical follow-up in all patients. RESULTS: Baseline parameters did not differ statistically. The Taxus-Express stent resulted in a significantly larger MLD and a significantly lower percent diameter stenosis post intervention compared to beta-brachytherapy, which both maintained until angiographic follow-up (primary endpoint 2.44 +/- 0.74 mm versus 1.73 +/- 0.74 mm, p < 0.0001). Therefore, Taxus-Express stents were associated with a lower angiographic restenosis rate compared with beta-brachytherapy, both for the target lesion (6.1% versus 17.4%) and the total segment (9.1% versus 23.9%). Moreover, use of Taxus-stent was associated with a clinical benefit based on a significantly lower MACE rate compared with beta-brachytherapy (p < 0.05). CONCLUSIONS: Paclitaxel-eluting Taxus-Express stents resulted in superior clinical and angiographic outcomes compared to intracoronary beta-brachytherapy with a liquid (188)Re filled balloon for treatment of restenosis within a bare-metal stent.

Radiosynthesis and evaluation of [11C]BTA-1 and [11C]3'-Me-BTA-1 as potential radiotracers for in vivo imaging of beta-amyloid plaques.

AIM: To evaluate the in vitro and in vivo characteristics of [N-methyl-(11)C]2-(4'-(methylaminophenyl)-benzothiazole ([(11)C]BTA-1) as well as [N-methyl-(11)C]2-(3'-methyl-4'-(methylamino)phenyl)-benzothiazole ([(11)C]3'-Me-BTA-1) as diagnostic markers of amyloid-beta (Abeta) in Alzheimer's disease (AD). MATERIAL, METHODS: Brain uptake and clearance was determined in wild-type mice. Binding affinities (K(i)) of [(11)C]BTA-1 and [(11)C]3'-Me-BTA-1 for aggregated Abeta(1-40) fibrils were assessed. Autoradiography was performed on brain sections of AD patients. To demonstrate binding specificity in vivo BTA-1 was injected i.p. in transgenic mice (Tg2576). Brain sections were analysed consecutively. Additionally, a [(11)C]BTA-1 PET study of an AD patient and a healthy control was performed. RESULTS: In mice brain uptake and clearance of [(11)C]BTA-1 is compatible with the half life of (11)C (2 min: 12.7 % ID/g; 30 min: 4.6% ID/g). In contrast clearance rate of [(11)C]3'-Me-BTA-1 is too slow (2 min 4% ID/g; 30 min 12% ID/g) to achieve sufficient clearance of free and non specifically bound radioactivity. K(i) of [(11)C]BTA-1 is 11 nmol/l and that of [(11)C]3'-Me-BTA-1 27 nmol/l. Both radioligands label Abeta selectively and specifically in AD patients and transgenic mice in vitro. The in vivo stained brain sections show a labelling of Abeta plaques. The AD patient has a higher prefrontal, parietal and striatal [(11)C]BTA-1 accumulation than the healthy control. Metabolite analysis revealed approximately 75% intact [(11)C]BTA-1 after 30min in plasma.[(11)C]BTA-1 is favourable for in vivo imaging of Abeta due to its rapid brain entry, sufficient clearance and good binding affinity for Abeta. CONCLUSION: The ability to label Abeta plaques in vivo in human subjects supports the suitability of [(11)C]BTA-1 as a plaque imaging agent.

Pre-gestational overweight in guinea pig sows induces fetal vascular dysfunction and increased rate of large and small fetuses.

In humans, obesity before and during pregnancy is associated with both fetal macrosomia and growth restriction, and long-term cardiovascular risk in the offspring. We aimed to determine whether overweighted pregnant guinea pig sows results in an increased fetal weight at term and the effects on the vascular reactivity in fetal systemic and umbilical arteries. Pregnant guinea pigs were classified as control (n=4) or high weight (HWS, n=5) according to their pre-mating weight, and their fetuses extracted at 0.9 gestation (~60 days). Segments of fetal femoral and umbilical arteries were mounted in a wire myograph, where the contractile response to KCl (5-125 mM), and the relaxation to nitric oxide synthase-dependent agents (insulin, 10-10-10-7 and acetylcholine, 10-10-10-5) and nitric oxide [sodium nitroprusside (SNP), 10-10-10-5] were determined. Fetuses from HWS (HWSF) were grouped according to their body weight as low (85 g) fetal weight, based on the confidence interval (76.5-84.9 g) of the control group. No HWSF were observed in the normal range. Umbilical arteries from HWSF showed a lower response to KCl and insulin compared with controls, but a comparable response with SNP. Conversely, femoral arteries from HWSF showed an increased response to KCl and acetylcholine, along with a decreased sensitivity to SNP. These data show that overweight sows have altered fetal growth along gestation. Further, large and small fetuses from obese guinea pig sows showed altered vascular reactivity at umbilical and systemic vessels, which potentially associates with long-term cardiovascular risk.