Dual-isotope SPECT imaging of striatal dopamine: a comparative study between never-treated and haloperidol-treated first-episode schizophrenic patients.

The aim of this dual-isotope SPECT imaging study was to evaluate striatal dopamine transporter (DAT) and D2 receptor availability in first-episode never-treated and haloperidol-treated schizophrenic patients and whether the availability is associated with psychopathology. Twenty-four inpatients with a first acute schizophrenic episode were enrolled in the study; 12 of these patients were treated with haloperidol for 2 weeks before dual-isotope SPECT was performed, whereas the other 12 patients underwent the SPECT evaluation directly after enrollment. Twelve healthy control persons were also recruited and evaluated with the dual-isotope SPECT protocol. Psychopathology was assessed by the Positive and Negative Syndrome Scale and other scales. D2-radioligand binding did not differ between drug-naïve patients and the control group but was significantly lower in the haloperidol-treated group. DAT availability was also significantly lower in the haloperidol patients than in the other two groups and differed significantly between drug-naïve, positive-syndrome-type patients and healthy controls. The data obtained with the new dual-isotope SPECT technique reveal a direct effect of haloperidol at the D2 and DAT receptor level.

Sentinel node biopsy by indocyanine green retention fluorescence detection for inguinal lymph node staging of anal cancer: preliminary experience.

BACKGROUND: There is some evidence that sentinel lymph node (SLN) biopsy guided by dye injection and/or radioisotopes can improve staging of inguinal lymph nodes (LNs) in anal cancer. This study was performed to investigate the feasibility of fluorescence detection of SLN and lymphatic mapping in anal cancer. METHODS: Twelve patients with anal cancer without evidence for inguinal LN involvement were included in the study. Intraoperatively, all patients received a peritumorous injection of 25 mg indocyanine green (ICG) for fluorescence imaging of the SLN with a near-infrared camera. For comparison, conventional SLN detection by technetium-(99)m-sulfur radiocolloid injection in combination with blue dye was also performed in all patients. The results of both techniques and the effect on the therapeutic regimen were analyzed. RESULTS: Overall, ICG fluorescence imaging identified at least one SLN in 10 of 12 patients (detection rate, 83%). With the combination of radionuclide and blue dye, SLN were detected in 9 of 12 patients (detection rate, 75%). Metastatic involvement of the SLN was found in 2 of 10 patients versus 2 of 9 patients. Patients with metastatic involvement of the SLN received extended radiation field with inguinal boost. CONCLUSIONS: ICG fluorescence imaging allows intraoperative lymphatic mapping and transcutaneous SLN detection for selective biopsy of inguinal SLN in anal cancer. This technique should be further evaluated in comparative studies with larger patient numbers.

Sentinel lymph node biopsy in breast cancer guided by indocyanine green fluorescence.

BACKGROUND: Sentinel lymph node (SLN) biopsy with radioisotope and blue dye has been used successfully for axillary staging in breast cancer. This study evaluated the feasibility of fluorescence detection of SLNs with indocyanine green (ICG) for lymphatic mapping and SLN biopsy. METHODS: Thirty women with breast cancer had a periareolar injection of ICG for fluorescence detection of SLN using a near-infrared camera. Twenty also received (99m)Tc-labelled sulphur radiocolloid for SLN scintigraphy. All patients underwent axillary lymph node dissection. Detection rate and sensitivity of both methods were the study endpoints. RESULTS: Visualization of lymphatic vessels by fluorescence detection depended on the dose of ICG. ICG imaging identified SLNs in 29 of 30 women (detection rate 97 per cent). Nineteen of 21 patients had metastatic SLN involvement (sensitivity 90 per cent) with false-negative results in two. Among the 20 patients who had both methods, ICG fluorescence and radiocolloid identified SLNs in 20 and 17 patients respectively. Metastatic lymph nodes were diagnosed in 12 and ten of 13 patients (sensitivity 92 and 77 per cent). False-negative rates were 8 and 23 per cent respectively. CONCLUSION: ICG fluorescence allowed transcutaneous imaging of lymphatic vessels and SLN detection, thus combining the advantages of radioisotope and blue dye methods.

Striatal D2/D3 receptor occupancy, clinical response and side effects with amisulpride: an iodine-123-iodobenzamide SPET study.

INTRODUCTION: Amisulpride appears to be an effective atypical agent for treating schizophrenia in a dose-dependent manner. METHODS: 29 patients suffering from schizophrenia or schizoaffective disorder were treated with a broad dose range of amisulpride (50-1 200 mg/day, mean: 455.2+/-278.8 mg/day). After 2 weeks, brain single photon emission tomography (SPET) scans were performed two hours after intravenous injection of 185 MBq [123I]IBZM. Clinical evaluations and ratings of extrapyramidal symptoms were performed at baseline and after steady state treatment of two weeks with amisulpride. RESULTS: In patients treated with amisulpride, specific binding of [123I]IBZM to D2 receptors was significantly decreased (p<0.001) compared to healthy controls. D2 receptor blockade correlated well with administered doses and plasma concentrations of amisulpride. Extrapyramidal side effects, which had to be treated with biperiden, were observed in 31% of the patients. Clinical response was very good, without correlation between the response and striatal D2 occupancy. DISCUSSION: Within the first two weeks of treatment with the atypical antipsychotic amisulpride a significant occupancy of striatal postsynaptic dopamine D2 receptors was achieved. At the same time amisulpride shows an excellent tolerability with good efficacy.

Lymphatic mapping and sentinel lymph node biopsy in epidermoid carcinoma of the anal canal.

AIM: Although 15-25% of patients with anal cancer present with superficial inguinal lymph node metastases but the routine application of groin irradiation is controversial because of serious side effects. Inguinal sentinel lymph node biopsy (SLNB) can be used to select patients appropriately for inguinal radiation. The study evaluates the efficiency and clinical impact of SLNB. METHODS: Forty patients with anal cancer underwent 1 ml Tc(99m)-Nanocolloid injection in four sites around the tumour. Patients with inguinal radio colloid enrichment were selected for sentinel lymph node biopsy (SLNB). Lymph node status was examined by haematoxylin and eosin (H&E) as well as immunohistochemistry-staining. All SLN-positive patients were scheduled for inguinal radiation; SLN-negative patients with T1 and early T2 tumours were not scheduled for inguinal radiation. RESULTS: SLN were detected in 36/40 patients. Three common patterns of lymphatic drainage were observed: mesenterial, iliacal and inguinal. Twenty patients with inguinal SLN underwent SLN-biopsy. 6/20 patients were SLN-positive. In 10/20 patients SLNB altered the therapy plan--four patients with T1-tumours and positive SLN had additional groin irradiation, whereas 6 patients with small T2-tumors and tumour-free inguinal SLN did not undergo inguinal irradiation. CONCLUSIONS: Inguinal sentinel node biopsy in anal cancer is efficient and could assist in the decision for inguinal radiation. The validity and safety of the proposed therapeutic algorithm has to be proven by a larger, prospective study.

Dual-isotope SPECT imaging of striatal dopamine: first episode, drug naïve schizophrenic patients.

OBJECTIVE: The aim of this investigation was to evaluate the usefulness of a dual-isotope SPECT technique to assess simultaneously striatal dopamine binding structures - presynaptic dopamine transporter (DAT) and postsynaptic dopamine D(2) receptor - in first-episode, drug-naive schizophrenic patients compared to healthy control persons. Additionally, relations between radioligand binding to DAT and D(2) and positive symptoms were assessed. METHODS: Twenty acutely ill inpatients suffering from a first acute schizophrenic episode and 12 healthy control persons participated in the study. Patients were naïve with respect to neuroleptic or antidepressant medication. A dual-isotope SPECT protocol was performed using combined application of [99mTc]TRODAT-1 and [123I]IBZM. On the day of SPECT, psychopathology was assessed in the patient group by PANSS rating. RESULTS: In the patient but not in the healthy control group there was a significant correlation between DAT and D(2) receptor availability. Patients with predominant positive symptoms (n=12) had a significantly higher DAT availability compared to the healthy control group. An inverse correlation between DAT and D(2) availability and the extent of "delusions", "conceptual disorganization", and "hallucinatory behaviour" could be demonstrated. DISCUSSION: The data obtained with this dual-isotope SPECT technique show a change in interaction between striatal DAT and D(2) receptor in first-episode, never-treated schizophrenic patients. Additionally, an association between dopamine transmission and the core symptoms of the acute psychotic syndrome was found.

Sentinel node biopsy in synovial sarcoma.

AIMS: To examine the relevance of sentinel node biopsy in patients with synovial sarcoma. METHODS: Between July 2004 and February 2007 11 consecutive patients with synovial sarcoma treated in our clinic underwent sentinel node biopsy after a preoperative lymphoscintigraphy. A handheld gamma-probe was used during the procedure to identify the sentinel nodes, which were then resected and submitted for histopathologic evaluation. RESULTS: At least one sentinel node was identified in every patient. Of a total of 15 sentinels, one was positive and 14 negative. The patient with the positive sentinel underwent a regional lymph node dissection and remains disease-free 17 months later. One patient developed regional nodal metastases despite negative sentinel node biopsy and died 12 months after the procedure. No biopsy-associated complications were observed. CONCLUSIONS: Sentinel node biopsy can be successfully and safely applied to patients with synovial sarcoma. Further prospective studies are required to determine the optimal treatment approach, the false negative rate and the prognostic significance of a positive sentinel node biopsy.

Impact of patient- and disease-specific factors on SLNB in breast cancer patients. Are current guidelines justified?

BACKGROUND: The evidence on which to base guidelines for sentinel lymph node biopsy (SLNB) in breast cancer is still limited. In order to facilitate the further implementation of renewed guidelines, we evaluated patient- and disease-specific factors for their impact on the results of SLNB. MATERIALS AND METHODS: Prospective data acquisition from patients undergoing surgery for primary invasive breast cancer was performed. All patients underwent SLNB using the radiocolloid or the combined technique. The association of patient- and disease-specific factors to detection rate and false-negative rate was calculated using univariate and multivariate analyses (P < 0.05 considered as significant). Calculation of the false-negative rate was based on patients who underwent a backup axillary dissection. RESULTS: Among 455 consecutively enrolled patients, a significant inverse association to the detection rate was found for extracapsular extension of non-SLN metastases, body mass index (BMI), number of involved lymph nodes, pT category, tumor size, and age. A significant association to the false-negative rate to identify macrometastases was found for pT category, tumor size, and grading. Other factors, such as prior surgery, multicentric tumor growth, or vascular invasion, showed no influence. A cut-point analysis revealed that a tumor size of 2 cm separated the collective of patients with the highest significance in regard to the false-negative rate (9% vs. 25%). CONCLUSION: Our results indicate that SLNB can be safely used in elderly and obese patients with multicentric tumors and those having undergone prior surgery for benign breast disease. However, the method should be applied with caution in patients with tumors larger than 2 cm.

Striatal dopamine transporter availability is associated with the productive psychotic state in first episode, drug-naive schizophrenic patients.

OBJECTIVE: Supposing a "hyperdopaminergic State" associated at least with acute psychotic illness phases in schizophrenia, a direct relationship between striatal dopamine metabolism and the core psychopathological symptoms rarely can be provided. Recently, a new SPECT ligand to the presynaptic dopamine transporter (DAT) was introduced. Association of DAT availability and the acute psychotic syndrome is now demonstrated in a large cohort of first episode, never treated schizophrenic patients. METHODS: Twenty-eight inpatients suffering from a first acute exacerbation of schizophrenia and 12 healthy control subjects underwent SPECT scanning with the new radioligand [(99m)Tc]TRODAT-1. On the day of SPECT, psychopathology was assessed using specific scales including PANSS. RESULTS: There was no significant difference in [(99m)Tc]TRODAT-1 specific binding to the striatal DAT comparing both groups. The extend of hallucinations was significantly inversely correlated with DAT availability in patients with a predominantly positive syndrome type. DISCUSSION: Our data support evidence that differences in presynaptic dopaminergic activity in schizophrenic patients are associated with the extend of the acute psychotic syndrome. [(99m)Tc]TRODAT-1 seems to be a useful agent for in vivo assessment of a psychopathological association with dopamine metabolism.

The striatal dopamine transporter in first-episode, drug-naive schizophrenic patients: evaluation by the new SPECT-ligand[99mTc]TRODAT-1.

Following the current hypothesis that acute schizophrenic psychotic illness is associated with a striatal 'hyperdopaminergic state', presynaptic integrity and dopamine transporter (DAT) density in first-episode, neuroleptic-naive schizophrenic patients was measured by single-photon-emission-tomography (SPECT) and compared with that in healthy control subjects. A new SPECT-ligand for assessment of the striatal DAT, the Technetium-99m-labelled tropane TRODAT-1 ([99mTc]TRODAT-1), was used. Ten inpatients suffering from a first acute schizophrenic episode and 10 age- and sex-matched healthy control subjects underwent SPECT with [99mTc]TRODAT-1. On the day of SPECT, psychopathological ratings were performed with the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS) and Schedule for Assessment of Negative Symptoms (SANS). Patients had not previously received any neuroleptic or antidepressant medication. Mean specific TRODAT-1 binding in the striatum did not differ significantly between the patient and the age- and sex-matched control group (1.25 vs. 1.28). Variance was significantly higher in the patient group. The data obtained with the new ligand in first-episode, drug-naive schizophrenic patients are in line with the PET results from the group of Laakso et al. in a comparable patient sample. [99mTc]TRODAT-1 seems to be a valuable new SPECT-ligand in the evaluation of the presynaptic site of the striatal dopaminergic synapse in schizophrenia.

Colorectal cancer patients before resection of hepatic metastases. Impact of (18)F-FDG PET on detecting extrahepatic disease.

AIM: Evaluation of the role of FDG-PET in comparison to conventional staging methods for detecting extrahepatic tumour deposits prior to resection of liver metastases. PATIENTS, METHODS: In our prospective study, 58 patients (24 women, 34 men; age 33-81 years) with liver metastases of colorectal carcinoma underwent FDG-PET. Images were acquired in 3D-mode including transmission scans and reconstructed iteratively. For conventional staging all patients underwent abdominal ultrasound, helical computed tomography (CT) of the thorax and abdomen, and colonoscopy/rectoscopy. A preliminary therapeutic decision was established without knowledge of the FDG-PET findings. Thereafter, it was revised or confirmed according to the results of FDG-PET. RESULTS: In 3/58 patients extrahepatic tumour deposits were concordantly identified with both conventional staging methods and FDG-PET. However, in one case, both conventional methods and FDG-PET were false positive regarding pulmonary metastases. In 12/58 patients, nothing but FDG-PET detected extrahepatic tumour masses, which were later confirmed either by histology or follow-up. CONCLUSION: Our study suggests that in 21% of patients exclusively FDG-PET is an appropriate diagnostic tool to reveal extrahepatic metastases or local recurrence of colorectal carcinoma. Our results demonstrate that FDG-PET provides relevant additional information for accurate therapeutic planning as compared to the conventional combination of staging methods. Therefore, FDG-PET has to exert a decisive influence on the decision for resection of hepatic metastases.

[18F]FDG imaging of head and neck tumours: comparison of hybrid PET and morphological methods.

The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose ([(18)F]FDG) imaging of head and neck tumours using a second- or third-generation hybrid PET device. Results were compared with the findings of spiral computed tomography (CT) and magnetic resonance imaging (MRI), and, as regards lymph node metastasis, the ultrasound findings. A total of 116 patients with head and neck tumours (83 males and 33 females aged 27-88 years) were examined using a hybrid PET scanner after injection of 185-350 MBq of [(18)F]FDG (Picker Prism 2000 XP-PCD, Marconi Axis gamma-PET(2) AZ). Hybrid PET examinations were performed in list mode using an axial filter. Reconstruction of data was performed iteratively. Ninety-six patients underwent CT using a multislice technique (Siemens Somatom Plus 4, Marconi MX 8000), 18 patients underwent MRI and 100 patients were examined by ultrasound. All findings were verified by histology, which was considered the gold standard, or, in the event of negative histology, by follow-up. Correct diagnosis of the primary or recurrent lesion was made in 73 of 85 patients using the hybrid PET scanner, in 50 of 76 patients on CT and in 7 of 10 patients on MRI. Hybrid PET successfully visualised metastatic disease in cervical lymph nodes in 28 of 34 patients, while 23 of 31 were correctly diagnosed with CT, 3 of 4 with MRI and 30 of 33 with ultrasound. False positive results regarding lymph node metastasis were seen in three patients with hybrid PET, in 14 patients with CT and in 13 patients with ultrasound. MRI yielded no false positive results concerning lymph node metastasis. In one patient, unrecognised metastatic lesions were seen on hybrid PET elsewhere in the body (lung: n=1; bone: n=1). Additional malignant lesions at sites other than the head and neck tumour were found in three patients (one patient with lung cancer, one patient with pelvic metastasis due to a carcinoma of the prostate and one patient with pulmonary metastasis due to breast cancer). It is concluded that [(18)F]FDG PET with hybrid PET scanners is superior to CT and MRI in the diagnosis of primary or recurrent lesions as well as in the assessment of lymph node involvement, whereas it is inferior to ultrasound in the detection of cervical lymph node metastasis.

Staging of recurrent and advanced lung cancer with 18F-FDG PET in a coincidence technique (hybrid PET).

The aim of this study was to evaluate [18F]fluorodeoxyglucose ( F-FDG) imaging of recurrent or inoperable lung cancer using a hybrid positron emission tomography (PET) device of the third generation. Examinations were compared with the results of conventional staging. Thirty-six patients suffering from recurrent or primarily inoperable lung cancer (29 men, seven women; age 64.8+/-12.0 years) were examined using hybrid PET (Marconi Axis gamma-PET ) 60 min after injection of 370 MBq F-FDG. The data obtained were reconstructed iteratively. All patients received a computed tomography (CT) scan using either the spiral or multislice technique. All lesions suspicious for primary or recurrent tumour were verified by biopsy; mediastinal lymph nodes were considered as malignant, when positive histology or a small axis diameter of greater than 1 cm measured with CT in addition to progression of clinical course was found. Distant metastases were diagnosed by CT and bone scintigraphy. Using hybrid PET all lesions showed a focally elevated glucose metabolism. Lymph node involvement of the ipsilateral peribronchial and hilar station (N1) was identified in 24/26 cases (92%), in 26/29 cases (90%) of ipsilateral central manifestation (N2) and in 11/13 (85%) cases of central contralateral or supraclavicular lymphatic infestation (N3). Pulmonary spread in hybrid PET was found in 4/8 cases (50%), whereas mainly lung metastases with a diameter of 1.5 cm and smaller were missed. Pleural involvement diagnosed by CT was verified in 4/5 patients. All four patients with bony metastases in conventional staging also presented with positive findings in hybrid PET (8/9 lesions). Concordance with conventional staging was found in 28/36 of patients (78%). In 4/36 patients (11%) unknown sites of tumour were detected leading to therapeutic consequences in three patients after radiological confirmation. Hybrid PET would have led to an understaging in four cases (11%), resulting theoretically in inefficient treatment in two patients. Hybrid PET for F-FDG imaging in the staging of recurrent or primarily inoperable lung cancer supplied equal (78%) or more information (11%) compared to conventional staging procedures. Using the information of hybrid PET alone, 11% of the patients would have been understaged. We conclude that hybrid PET has the potential for use as an additional staging tool in this subgroup of patients, providing supplementary information compared to conventional staging modalities.

Striatal dopamine D2 receptor binding of risperidone in schizophrenic patients as assessed by 123I-iodobenzamide SPECT: a comparative study with olanzapine.

The aim of this investigation was to compare the degree of striatal dopamine-(D2) receptor blockade by two atypical antipsychotic drugs, risperidone and olanzapine. The percentage of D2 receptor occupancy during treatment was calculated by comparing the results of 123I-iodobenzamide SPECT with those from healthy control subjects. Twenty inpatients suffering from schizophrenia or schizoaffective psychosis according to DSM IV/ICD-10 criteria were treated with clinically recommended doses of risperidone and compared with 13 inpatients treated with up to 20 mg olanzapine. Neuroleptic dose and D2 receptor blockade correlated strongly for both risperidone (Pearson r = -0.86, p = 0.0001) and olanzapine (Pearson r = -0.77, p = 0.002). There was no significant difference between the D2 receptor occupancy of the two substances when given in the clinically recommended dose range (unpaired t-test, t = -0.112, p = 0.911).

[Diagnosis of initial changes in the hand of patients with rheumatoid arthritis--comparison between low-field magnetic resonance imaging, 3-phase bone scintigraphy and conventional x-ray]. / Diagnostik initialer Veränderungen an der Hand bei rheumatoider Arthritis--Vergleich der Niederfeld-Magnetresonanz-Tomographie mit 3-Phasen-Skelettszinti-graphie und Projektionsradiographie.

UNLABELLED: Besides conventional X-rays, in the diagnostic work up of initial changes in patients suffering from rheumatoid arthritis (RA), 3-phase bone scintigraphy (3P-Sz) is as well established as magnetic resonance imaging (MRI). The aim of this study was to compare the diagnostic value of the newly developed low field MRI with the proven methods X-rays and 3P-Sz. METHODS: 65 patients (47f, 18m; 20-86 yrs) were studied on a one day protocol with 3P-Sz (550 MBq Tc-99m DPD), MRI and X-rays of the hands. Images were visually analysed by two blinded nuclear medicine physicians and radiologists and classified as a) RA-typical, b) inflammatory, non-RA-typical and c) non inflammatory changes. All methods were compared to 3P-Sz as golden standard. RESULTS: In comparison to 3P-Sz, low field MRI presents with almost equal sensitivity and specificity in rheumatoid-typical and inflammatory changes. Conventional X-rays revealed in arthritis-typical changes as well as in inflammatory changes a significantly lower sensitivity and also a lower negative predictive value while specificity equals the one of MRI. Quantitative analysis of 3P-Sz using ROI-technique unveiled significantly higher values in patients with rheumatoid arthritis than in those with no inflammatory changes. CONCLUSION: MRI represents an equally sensitive method in the initial diagnosis of rheumatoid-typical and inflammatory changes in the region of the hands as compared to the 3P-Sz. Besides the basic diagnosis with conventional X-rays, 3P-Sz is still the recommended method of choice to evaluate the whole body when RA is suspected. Additionally, quantitative analysis of the 3P-Sz using the ROI technique in the region of the hands reveals statistically significant results and should therefore be taken into account in the assessment of inflammatory changes.

[[F-18]FDG imaging of head and neck tumors: comparison of hybrid PET, dedicated PET and CT]. / [F-18]FDG-Bildgebung bei Kopf-Hals-Tumoren: vergleichende Untersuchungen mit Hybrid-PET, Ring-PET und CT.

AIM: Aim of the study was to evaluate [F-18]FDG imaging of head and neck tumors using a Hybrid-PET device of the 2nd or 3rd generation. Examinations were compared to dedicated PET and Spiral-CT. METHODS: 54 patients suffering from head and neck tumors were examined using dedicated PET and Hybrid-PET after injection of 185-350 MBq [F-18]FDG. Examinations were carried out on the dedicated PET first followed by a scan on the Hybrid-PET. Dedicated PET was acquired in 3D mode, Hybrid-PET was performed in list mode using an axial filter. Reconstruction of data was performed iteratively on both, dedicated PET and Hybrid-PET. All patients received a CT scan in multislice technique. All finding have been verified by the goldstandard histology or in case of negative histology by follow up. RESULTS: Using dedicated PET the primary or recurrent lesion was correctly diagnosed in 47/48 patients, using Hybrid-PET in 46/48 patients and using CT in 25/48 patients. Metastatic disease in cervical lymph nodes was diagnosed in 17/18 patients with dedicated PET, in 16/18 patients with Hybrid-PET and in 15/18 with CT. False positive results with regard to lymph node metastasis were seen with one patient for dedicated PET and Hybrid-PET, respectively, and with 18 patients for CT. In a total of 11 patients unknown metastatic lesions were seen with dedicated PET and with Hybrid-PET elsewhere in the body. Additional malignant disease other than the head and neck tumor was found in 4 patients. CONCLUSION: Using Hybrid-PET for [F-18]FDG imaging reveals a loss of sensitivity and specificity of about 1-5% as compared to dedicated PET in head and neck tumors. [F-18]FDG PET with both, dedicated PET and Hybrid-PET is superior to CT in the diagnosis of primary or recurrent lesions as well as in the assessment of lymph node involvement.