[Gastroenteropancreatic neuroendocrine neoplasms-Heterogeneity, management and perspectives of treatment and research]. / Gastroenteropankreatische neuroendokrine Neoplasien ­ Heterogenität, Management und Perspektiven der Versorgung und Forschung.

The term neuroendocrine neoplasms (NEN) encompasses a molecularly and biologically very heterogeneous group of tumors, which have in common their origin in neuroendocrine cells. The also very heterogeneous subgroup of gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) is the best classified and investigated group. This article provides a systematic review of the current classification, diagnostics and treatment options of GEP-NEN. In order to achieve a better overview, it was consciously decided not to use an approach based on the primary localization. Instead, a thematic organization according to classification, clinical phenotype, diagnostics and treatment was chosen.

[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).

Striatal dysfunction in X-linked dystonia-parkinsonism is associated with disease progression.

BACKGROUND AND PURPOSE: X-linked dystonia-parkinsonism (XDP) is an inherited neurodegenerative adult-onset movement disorder associated with striatal atrophy. As the dopaminergic system has not yet been systemically studied in this basal ganglia model disease, it is unclear whether nigrostriatal dysfunction contributes to parkinsonism in XDP. METHODS: Pre- and post-synaptic dopaminergic function was assessed in XDP. A total of 10 123 jod-benzamide (IBZM) single-photon emission computed tomography (SPECT) images were obtained for nine patients aged 42.3 ± 9.5 years (SD; range 30-52) and one asymptomatic mutation carrier (38 years), and four ioflupane (FP-CIT) SPECT images were obtained for four patients, aged 41.5 ± 11.6 years (range 30-52 years). Structural magnetic resonance imaging was also performed for all mutation carriers and 10 matched healthy controls. RESULTS: All patients were men who suffered from severe, disabling segmental or generalized dystonia and had varying degrees of parkinsonism. IBZM SPECT images were pathological in 8/9 symptomatic patients with distinct reduced post-synaptic tracer uptake in the caudate nucleus and putamen, and unremarkable in the asymptomatic mutation carrier. Longer disease duration was correlated with lower IBZM binding ratios. All subjects exhibited slightly reduced FP-CIT uptake values compared to controls for each analyzed region (-37% to -41%) which may be linked to basal ganglia volume loss. Visual inspection revealed physiological FP-CIT uptake in 1/4 patients. CONCLUSIONS: This nuclear imaging study provides evidence that the functional decline of post-synaptic dopaminergic neurotransmission is related to disease duration and ongoing neurodegeneration. Given the severe striatal cell loss which could be verified with post-synaptic nuclear imaging, both parkinsonism and dystonia in XDP are probably mainly due to striatal dysfunction.

Salivary gland scintigraphy in patients suffering from severe keratoconjunctivitis sicca. Evaluation of the viability of submandibular glands before and after transfer into the temporal fossa.

UNLABELLED: Low tear production or elevated tear evaporation can lead to severe keratoconjunctivitis sicca. In patients with this disease, the transfer of an autologous submandibular gland into the temporal fossa is currently the most common surgical lacrimal gland substituting procedure. AIM: We compared the pre- and postoperative viability of transferred submandibular glands. PATIENTS, METHODS: Altogether 16 submandibular glands had been transferred in 12 patients. The graft's viability was evaluated before and 0.5-1, 1-6 and 8-12 months after transplantation by dynamic salivary gland scintigraphies after application of 40-50 MBq 99mTc-pertechnetate. Quantitative analysis was performed by calculation and comparison of the glandula submandibularis-to-background-ratio (SBR) and the transplant-to-background-ratio (TBR). The scintigraphic results were correlated with the clinical follow-up. RESULTS: All grafts remained viable during clinical follow-up. Salivary gland scintigraphy yielded 15 true positive results and 1 false-negative result. Comparison of presurgical SBR and postsurgical TBR showed good correlation with the clinical course. In 10 patients at least one transplant-reduction was necessary due to excessive epiphora occurring averagely 8 months after transplantation. CONCLUSION: Our results show that salivary gland scintigraphy very exactly reflects the morphological and biochemical postsurgical changes in a transferred submandibular gland. Thus, it is a reliable tool to exactly and objectively evaluate the viability of the grafts in the postsurgical course.

[Peptide receptor radionuclide therapy for patients with somatostatin receptor expressing tumours. German Guideline (S1)]. / Peptidrezeptor-Radionuklidtherapie Somatostatinrezeptor-exprimierender Tumore. DGN-Leitlinie (S1).

This document describes the guideline for peptide receptor radionuclide therapy (PRRT) published by the German Society of Nuclear Medicine (DGN) and accepted by the Association of the Scientific Medical Societies in Germany (AWMF) to be included in the official AWMF Guideline Registry. These recommendations are a prerequisite for the quality management in the treatment of patients with somatostatin receptor expressing tumours using PRRT. They are aimed at guiding nuclear medicine specialists in selecting likely candidates to receive PRRT and to deliver the treatment in a safe and effective manner. The recommendations are based on an interdisciplinary consensus. The document contains background information and definitions and covers the rationale, indications and contraindications for PRRT. Essential topics are the requirements for institutions performing the therapy, e. g. presence of an expert for medical physics, intense cooperation with all colleagues involved in the treatment of a patient, and a certificate of instruction in radiochemical labelling and quality control are required. Furthermore, it is specified which patient data have to be available prior to performance of therapy and how treatment has to be carried out technically. Here, quality control and documentation of labelling are of great importance. After treatment, clinical quality control is mandatory (work-up of therapy data and follow-up of patients). Essential elements of follow-up are specified in detail. The complete treatment inclusive after-care has to be realised in close cooperation with the involved medical disciplines. Generally, the decision for PRRT should be undertaken within the framework of a multi-disciplinary tumour board.

[Diagnostics and therapy for neuroendocrine neoplasia of an unknown primary - a plea for open exploration]. / Diagnostik und Therapie bei neuroendokrinen Neoplasien mit unklarem Primarius - ein Plädoyer für die offene Exploration.

BACKGROUND: Neuroendocrine neoplasia (NEN) are a rare and heterogenous tumour entity. The subgroup with unknown primary tumour (N-CUP) seems to have a worse prognosis as resection of the primary is necessary for cure. The diagnostics and therapeutic algorithms for N-CUP in a German single centre are presented. PATIENTS/METHODS: Analysis of the surgical databank showed 35 cases of N-CUP in 261 cases with NEN from gastroenteropancreatic and lung origin over 2 decades (03/1990-03/2011). Three groups were built: K1 - primary detection after operative exploration (n = 10), K2 - unknown primary after operative exploration (n = 10) and K3 - no operative exploration for various reasons (n = 13). RESULTS: Initially 13.4 % (35/261) of patients presented as N-CUP, after intensified diagnostics 12.7 % (33/261) and after operative exploration 8.8 % (23/261) remained with unknown primary tumour. The sex ratio was 1 : 1, the median age is significantly higher in N-CUP [63.8 years (y) vs. 55.9 y, p = 0.004), the 5-year-survival is lower (58 vs. 72 %, n. s.). compared to NEN with known primary. Operative exploration was performed in 60.6 % (20/33), 30 % (6/20) of them were found to have inoperable situations, in 20 % (4/20) single site metastases were removed completely and in 50 % (10/20) a primary tumour was detected (8 × midgut, 2 × pancreas) intraoperatively. In these cases 70 % (7/10) got complete tumour resection (R0) and in 30 % (3/10) primary tumour resection with debulking of liver metastasis was done. In K3 (39.4 %, 13/33) most patients [69.2 % (9/13)] were treated with chemotherapy. The median age in K1 was significantly lower than in K3 (54.9 y vs. 68.3 y, p = 0.028), male dominance was seen in K3 (3,3 : 1, n. s.). The average Ki-67 index was 4.3, 23.8 and 53 % in K1, K2 and K3 (p < 0.0001 for K1 and K3 and p = 0.035 for K2 and K3), respectively. The death rate was 20, 30 and 76.9 % in K1, K2 and K3, respectively. CONCLUSION: Primary tumours of the midgut and pancreas are often found in the subset of well differentiated neuroendocrine CUP syndrome after open surgical exploration. A high rate of complete tumour resection and cure can be achieved in these cases. After common diagnostic tools (CT, MRI and somatostatin receptor scintigraphy), immunhistochemistry can give important hints (CDX-2 for midgut, TTF-1 for lung and thyroid) for a primary lesion. Also in single site metastasis without primary tumour detection a good clinical outcome is seen after complete resection.

[Myeloablative radioimmunotherapy with 188Re-CD66mAb before stem cell transplantation. No increase of proinflammatory cytokine levels of TNF-alpha]. / Myeloablative Radioimmuntherapie mit 188Re-CD66mAb vor Stammzelltransplantation: Kein Anstieg proinflammatorischer Zytokinspiegel von TNF-alpha.

AIM: Tumour necrosis factor-alpha (TNF-alpha) serum levels may increase due to intensive conditioning regimes with high-dose-chemotherapy and total body irradiation (TBI) before stem cell transplantation. This increases the risk for developing acute graft versus host disease (aGvHD) after stem cell transplantation. In this prospective study we investigated the influence of radioimmunotherapy with 188Re-CD-66-mAb on changes on TNF-alpha serum levels. PATIENTS, METHODS: In 18 patients we measured TNF-alpha before and up to 96 hours after radioimmunotherapy, in 2 patients in addition following TBI, in 9 patients also following chemotherapy. For measuring TNF-alpha we used an automated immunochemiluminescence assay (Immulite 1000 DPC Biermann, Bad Nauheim). The mean follow up period to record incidence of aGVHD was 100 days after stem cell transplantation. RESULTS: Compared to the basal levels before, the levels of TNF-alpha after conditioning with 188Re-CD-66-mAb did not increase significantly and remained in the physiological range. In contrast, these initial physiological cytokine levels increased and became pathological following 48 h after total body irradiation (13.2+/-6.6 pg/ml) and chemotherapy (10.8+/-15.7 pg/ml). In our study we found a low incidence of aGvHD (22.2%, n=4/18). CONCLUSION: These results demonstrate that additional conditioning therapy with 188Re-CD-66-mAb does not increase proinflammatory cytokine levels of TNF-alpha. This finding may indicate that additive radioimmunotherapy may not be a significant factor for increasing the rate of conditioning-associated aGvHD.

[[18F]-FDG-PET in the diagnostics of gastrointestinal tumors]. / [18F]-FDG-PET in der Diagnostik gastrointestinaler Tumoren.

Positron emission Tomography (PET) with 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) is a functional imaging technique with increasing value in special diagnostic fields of gastrointestinal tumours. In the initial staging of esophageal and gastric cancer, FDG-PET is useful in the staging of patients with advanced but local resectable disease. The detection of distant metastases results in an up-staging, and these patients should not be treated by surgery. Furthermore, FDG-PET is sufficient for monitoring early therapy responses after neoadjuvant treatment and enables one to select non-responders who may benefit from therapy alterations. Major indications for FDG-PET in patients with rectal carcinoma are therapy monitoring and diagnosis of relapses, especially the differentiation between tumour and scar and also the localisation of tumour manifestations in cases with increasing tumour markers. FDG-PET is very efficient in the imaging of pulmonal and hepatic metastases of colorectal cancer but not in lymph node staging. In diagnostic procedures for pancreatic carcinoma, FDG-PET can be recommended to explore the dignity of pancreatic lesions and in the imaging of tumour relapses. For gastrointestinal stroma tumours, FDG-PET is useful for the monitoring of therapy and the initial staging. For imaging of hepatocellular carcinoma and carcinoma of the gall bladder, FDG-PET is not sufficient.

Comparison of 68Ga-DOTATOC PET and 111In-DTPAOC (Octreoscan) SPECT in patients with neuroendocrine tumours.

PURPOSE: Neuroendocrine tumours (NETs) can be imaged with scintigraphy using radiolabelled somatostatin analogues. The aim of our study was to compare the value of (68)Ga-DOTATOC PET and (111)In-DTPAOC SPECT (Octreoscan) in the detection of NET manifestations. METHODS: Twenty-seven NET patients were prospectively examined. (68)Ga-DOTATOC PET and (111)In-DTPAOC SPECT were performed using standard techniques. Treatment was not applied in between. Mean and maximum standardised uptake values (SUVs) were calculated for PET findings. Tumour/non-tumour ratios were calculated for SPECT findings. Findings were compared by a region-by-region analysis and verified with histopathology, CT and MRI within 21 days. RESULTS: SUVs of positive lesions on (68)Ga-DOTATOC PET ranged from 0.7 to 29.3 (mean SUV) and from 0.9 to 34.4 (maximum SUV). Tumour/non-tumour ratios on (111)In-DTPAOC SPECT ranged from 1.8 to 7.3. In imaging lung and skeletal manifestations, (68)Ga-DOTATOC PET was more efficient than (111)In-DTPAOC SPECT. All discrepant lung findings and 77.8% of discrepant osseous findings were verified as true positive PET interpretations. In regional comparison of liver and brain, (68)Ga-DOTATOC PET and (111)In-DTPAOC SPECT were identical. In lymph nodes, the pancreas and the gastro-intestinal system, different values of the two techniques were not indicated in regional analyses. In a single patient, surgical interventions were changed on the basis of (68)Ga-DOTATOC PET findings. CONCLUSION: (68)Ga-DOTATOC PET is superior to (111)In-DTPAOC SPECT in the detection of NET manifestations in the lung and skeleton and similar for the detection of NET manifestations in the liver and brain. (68)Ga-DOTATOC PET is advantageous in guiding the clinical management.

FDG-PET in the initial staging of squamous cell oesophageal carcinoma.

UNLABELLED: Squamous cell oesophageal carcinoma is the most common carcinoma of the oesophagus worldwide. The tumour stage as most important prognostic factor determines the clinical management. AIM: of this study was to evaluate the value of FDG-PET 1. in imaging the primary tumour and 2. in N- and M-staging of squamous cell oesophageal carcinoma. PATIENTS, METHODS: In 20 patients with histological proven squamous cell carcinoma of the upper and middle oesophagus, FDG-PET was performed in standard technique prior to therapy. FDG uptake in the primary was determined by calculation of the SUVmax. NM-staging due to PET findings was performed as designated by the AJCC/UICC group classification and was compared with pathological and clinically based staging. Sensitivities, specificities and accuracies were calculated. RESULTS: In 19 of 20 patients, primary squamous cell oesopohageal carcinoma was detected by FDG-PET findings with a maximum SUV of 12.5 (mean) +/- 5.1 (median 11.5; range 4.8-23.8). One carcinoma in situ was missed. The sensitivity of FDG-PET in imaging the primary tumour was 96%. The sensitivities, specificities and accuracies were 20%, 100%, 58% for N-staging, and 60%, 86% and 93% for M-staging. PET findings caused changes of therapy in 5% (1 patient). CONCLUSIONS: FDG-PET was excellent in imaging the primary of squamous cell oesophageal carcinoma in stage T1-T4 and was efficient in M-staging. The low sensitivity in N-staging is of inferior clinical importance. The efficacy of FDG-PET seems to be not significantly be influenced by the histological subtype of oesophageal carcinoma.

[Radioimmunotherapy for treatment of acute myeloid leukaemia and myelodysplastic syndrome: conceptual chances]. / Radioimmuntherapien zur Behandlung der akuten myeloischen Leukämie und des myelodysplastischen Syndroms: Konzeptionelle Chancen.

The prognosis of patients with acute myeloid leukaemia (AML) has improved considerably by introduction of aggressive consolidation chemotherapy and haematopoietic stem cell transplantation (SCT). Nevertheless, only 20-30% of patients with AML achieve long-term disease-free survival after SCT. The most common cause of treatment failure is relapse. Additionally, mortality rates are significantly increased by therapy-related causes such as toxicity of chemotherapy and complications of SCT. Including radioimmunotherapies in the treatment of AML and myelodyplastic syndrome (MDS) allows for the achievement of a pronounced antileukaemic effect for the reduction of relapse rates on the one hand. On the other hand, no increase of acute toxicity and later complications should be induced. These effects are important for the primary reduction of tumour cells as well as for the myeloablative conditioning before SCT. This paper provides a systematic and critical review of the currently used radionuclides and immunoconjugates for the treatment of AML and MDS and summarizes the literature on primary tumour cell reductive radioimmunotherapies on the one hand and conditioning radioimmunotherapies before SCT on the other hand.

Targeted bone marrow irradiation in the conditioning of high-risk leukaemia prior to stem cell transplantation.

Disease recurrence following stem cell transplantation (SCT) remains a major problem. Despite the sensitivity of leukaemias to chemotherapy and irradiation, conventional conditioning before SCT is limited by significant organ toxicity. Targeted irradiation of bone marrow and spleen by radioimmunotherapy may provide considerable dose escalation, with limited toxicity to non-target organs. In this study, 27 patients with high-risk or relapsing leukaemia were treated with rhenium-188-labelled CD66a,b,c,e radioimmunoconjugates (188Re-mAb) specific for normal bone marrow in addition to conventional conditioning with high-dose chemotherapy and 12 Gy total body irradiation prior to SCT. A mean activity of 10.2+/-2.1 (range 6.9-15.8) GBq 188Re-mAb was administered intravenously. Acute side-effects were assessed according to the CTC classification and patient outcome was determined. Mean radiation doses (Gy; range in parentheses) to relevant organs and whole body were as follows: 13.1 (6.5-22) to bone marrow, 11.6 (1.7-31.1) to spleen, 5.0 (2.0-11.7) to liver, 7.0 (2.3-11.6) to kidneys, 0.7 (0.3-1.3) to lungs and 1.4 (0.8-2.1) to the whole body. Stem cells engrafted in all patients within 9-18 days post SCT. Acute organ toxicity of grade II or less was observed. During follow-up for 25.4+/-5.3 (range 18-34) months, 4/27 (15%) patients died from relapse, and 9/27 (33%) from transplantation-related complications. Fourteen patients (52%) are still alive and in ongoing complete clinical remission. Radioimmunotherapy with the bone marrow-seeking 188Re-labelled CD66 mAb can double the dose to bone marrow and spleen without undue extramedullary acute organ toxicity, when given in addition to high-dose chemotherapy and 12 Gy TBI before allogeneic SCT. This intensified conditioning regimen may reduce the relapse rate of high-risk leukaemia.

Rhenium 188-labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with high-risk acute myeloid leukemia or myelodysplastic syndrome: results of a phase I-II study.

The conditioning regimen prior to stem cell transplantation in 36 patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) was intensified by treating patients with a rhenium 188-labeled anti-CD66 monoclonal antibody. Dosimetry was performed prior to therapy, and a favorable dosimetry was observed in all cases. Radioimmunotherapy with the labeled antibody provided a mean of 15.3 Gy of additional radiation to the marrow; the kidney was the normal organ receiving the highest dose of supplemental radiation (mean 7.4 Gy). Radioimmunotherapy was followed by standard full-dose conditioning with total body irradiation (12 Gy) or busulfan and high-dose cyclophosphamide with or without thiotepa. Patients subsequently received a T-cell-depleted allogeneic graft from a HLA-identical family donor (n = 15) or an alternative donor (n = 17). In 4 patients without an allogeneic donor, an unmanipulated autologous graft was used. Infusion-related toxicity due to the labeled antibody was minimal, and no increase in treatment-related mortality due to the radioimmunoconjugate was observed. Day +30 and day +100 mortalities were 3% and 6%, respectively, and after a median follow-up of 18 months treatment-related mortality was 22%. Late renal toxicity was observed in 17% of patients. The relapse rate of 15 patients undergoing transplantation in first CR (complete remission) or second CR was 20%; 21 patients not in remission at the time of transplantation had a 30% relapse rate. (Blood. 2001;98:565-572)

Ki-67 immunostaining in pancreatic cancer and chronic active pancreatitis: does in vivo FDG uptake correlate with proliferative activity?

UNLABELLED: PET with 18F-FDG has been shown to be useful in the detection and staging of pancreatic cancer. However, whether FDG uptake is dependent on proliferative activity is still unclear. The aim of this prospective study was to evaluate a probable correlation between FDG uptake and proliferative activity in benign and malignant pancreatic tumors. METHODS: Our series consisted of 23 patients with pancreatic cancer and 9 patients with chronic active pancreatitis (CAP). FDG PET was performed within 2 wk before surgery, and standardized uptake values (SUVs) were calculated for benign and malignant pancreatic tumors. Patients were selected when focally increased FDG uptake in previously known pancreatic tumors was present. Proliferation fraction was measured in tissue specimens using the anti-Ki-67 antibody MIB-1. A computer-assisted imaging system was used for quantification of nuclear Ki-67 immunostaining. Immunohistochemical findings were correlated to SUVS: RESULTS: Pancreatic cancer showed both intense nuclear staining of Ki-67 (39% +/- 16%) and high FDG uptake (SUV = 3.6 +/- 1.6). However, no significant correlation was found between in vivo FDG uptake and Ki-67 immunoreactivity (P = 0.65). By contrast, Ki-67 nuclear staining was significantly lower (3.8% +/- 2.7%, P < 0.05) in CAP, whereas FDG uptake was in the same range as for pancreatic cancer (SUV = 3.5 +/- 1.8). CONCLUSION: FDG uptake did not correlate with proliferative activity in pancreatic cancer. Proliferative activity was tenfold higher in malignant pancreatic tumors than in benign tumors associated with CAP, whereas FDG uptake in vivo did not differ significantly. Thus, a PET tracer indicating cellular proliferation should better differentiate between cancer and inflammatory lesions than do metabolic markers such as FDG.

2-(fluorine-18)fluoro-2-deoxy-D-glucose positron emission tomography in the detection and staging of malignant lymphoma. A bicenter trial.

BACKGROUND: The authors undertook a prospective evaluation of the clinical value of 2-fluoro [18-]-2-deoxyglucose positron emission tomography (FDG-PET) in the detection and staging of malignant lymphoma compared with computed tomography (CT) and bone marrow biopsy (BMB). METHODS: Fifty-two consecutive patients with untreated malignant lymphoma were evaluated prospectively in a bicenter study. FDG-PET, CT, and BMB were performed for investigating lymph node/extranodal manifestations and bone marrow infiltration. Thirty-three percnt of the discrepant results were verified by biopsy, magnetic resonance imaging, or clinical follow-up (range, 4-24 month). RESULTS: Altogether, 1297 anatomic regions (lymph nodes, organs, and bone marrow) were evaluated. FDG-PET and CT scans were compared by receiver operating characteristic (ROC) curve analysis. The area under the ROC curve were as follows: lymph nodes, 0.996 (PET) and 0.916 (CT); extranodal, 0.999 (PET) and 0.916 (CT); supradiaphragmatic, 0.996 (PET) and 0.905 (CT); and infradiaphragmatic, 0.999 (PET) and 0.952 (CT). In these analyses, FDG-PET was significantly superior to CT (P < 0.05), except in infradiaphragmatic regions, in which the two methods produced equivalent results. In detecting bone marrow infiltration, FDG-PET was superior to CT and was equivalent to BMB. In 4 of 52 patients (8%), FDG-PET led to an upstaging and a change of therapy. CONCLUSIONS: Noninvasive FDG-PET is very accurate in the staging of malignant lymphoma. Compared with standard staging modalities (CT and BMB), PET was significantly superior and led to changes in the therapy regimen for 8% of patients.

Primary staging of lymphomas: cost-effectiveness of FDG-PET versus computed tomography.

The objective of this study was to measure the incremental cost-effectiveness of 2-(fluorine-18) fluorodeoxyglucose positron emission tomography (FDG-PET) versus computed tomography (CT) as diagnostic procedures in the primary staging of malignant lymphomas. The study was based on 22 patients of a clinical study who underwent the diagnostic procedures at Ulm University Hospital between April 1997 and May 1998. Direct costs of FDG-PET and CT, including staff, materials, investment, maintenance and overheads, were valued using a micro-costing approach. The effectiveness of both diagnostic procedures was measured as the percentage of correctly staged patients, given a gold standard for staging. The incremental cost-effectiveness ratio was the main outcome measure. Costs per patient of FDG-PET were 257 euros for FDG production and 704 euros for the FGD-PET scan, thus totalling 961 euros (in 1999 prices). The cost per patient of CT scans was found to be 391 euros. Verified PET findings induced an upstaging in four patients such that the effectiveness was 81.8% (18/22) for CT and 100% (22/22) for PET. Incremental cost-effectiveness ratios (interpreted as the additional costs of a more effective diagnostic strategy per additional unit of effectiveness, i.e. additionally correctly staged patient, achieved) were 478 euros per correctly staged patient for CT versus "no diagnostics" and 3133 euros for FDG-PET versus CT. Great potential for cost saving was identified in sensitivity analyses for FDG-PET. It is concluded that diagnostic accuracy and the costs of the diagnostic procedures could be measured precisely. FDG-PET was more accurate than CT. Decision-makers who consider savings in treatment costs significant may find the cost-effectiveness ratio of PET to lie within an acceptable range. However, more research is needed to assess the long-term treatment and cost effects of more accurate staging. There is significant potential to improve the technical efficiency of PET.

Different radiosensitivity of smooth muscle cells and endothelial cells in vitro as demonstrated by irradiation from a Re-188 filled balloon catheter.

There is an increasing interest in irradiation to control restenosis after balloon angioplasty by an internal radioactive source. Differences in radiosensitivity of the predominant cells of the human coronary artery (i.e. endothelial cells (HCAEC), smooth muscle cells from the media (HCMSMC) and from plaque material (HCPSMC), are issues of controversal discussion. Therefore, we investigated the graded inhibition of cells by irradiation from a balloon catheter filled with a high-energy beta-emitter (Rhenium-188) in vitro. HCPSMC, HCMSMC and HCAEC were cultured and irradiated with increasing dose from 7.5 to 37.5 Gy at a dose rate of 1.5+/-0.3 Gy/min. After irradiation, bromodeoxyuridine (BrdU) was added and cells were fixed 18 h later. In a limited field opposite to the balloon, the number of BrdU-positive cells were analysed in comparison to non-irradiated controls. Significant inhibition was demonstrated in HCPSMC and HCMSMC at 7.5 Gy while HCAEC needed 22.5 Gy for similar effects. The antiproliferative effect was dose dependent in all cell strains. The effect of irradiation with 22.5 Gy on smooth muscle alpha-actin, vimentin, and alpha-tubulin of HCPSMC and HCMSMC and on von Willebrand factor (vWF), vimentin, and alpha-tubulin of HCAEC was investigated by means of indirect immunofluorescence. Within 18 h after irradiation no effect on cytoskeletal components and vWF was documented. This in vitro study demonstrates that irradiation inhibits HCMSMC and HCPSMC at lower dose rates compared to HCAEC.