The use of radiolabelled human serum albumin and SPECT/MRI co-registration to study inflammation in the cavernous sinus of cluster headache patients.

A sterile inflammation in the cavernous sinus was hypothesized to underlie cluster headache (CH). Neurogenic inflammation is accompanied by the extravasation of plasma proteins in the surrounding tissue. We tested the hypothesis of an inflammatory process in the cavernous sinus in CH patients using 99mTc-human serum albumin (HSA) and single photon emission computed tomography (SPECT). Six patients with episodic CH were enrolled. After baseline imaging, CH attacks were induced by IV injection of nitroglycerin. The patients remained untreated for 20 min. A second SPECT was performed after successful treatment. Region of interest (ROI) analysis was performed on the basis of coregistered MRI/SPECT data. There was no statistical difference between the 99mTc-HSA uptake in the ipsilateral cavernous sinus before and after induction of an acute CH attack. There was no evidence for 99mTc-HSA extravasation in the cavernous sinus during the active episode as compared with the remission phase. Our results do not support the hypothesis of an inflammation in the cavernous sinus.

[Radiation exposure in (90)Y-Zevalin therapy: results of a prospective multicentre trial]. / Strahlenexposition bei der (90)Y-Zevalin-Therapie: Ergebnisse einer prospektiven multizentrischen Studie.

UNLABELLED: AIM of this study was the assessment of the radiation exposure from preparation and application of (90)Y-Zevalin, the measurement of the dose rate at the patient, the exposure of family members as well as the determination of the activity concentration in urine of patients. METHODS: Overall data from 31 therapeutic administrations carried out in four institutions were evaluated. During preparation and application of (90)Y-Zevalin the finger exposures of radiochemists, technicians, and physicians were measured. The dose rate of the patient was measured immediately after radioimmunotherapy. In patients treated in a nuclear medicine therapy unit, urine was collected over a two day period and the corresponding activity was determined. Family members of outpatients were asked to wear a dosimeter over a seven day period. RESULTS: During the preparation we found a maximum skin dose of 6 mSv at the average, and during application of 3 mSv, respectively. After administration of (90)Y the dose rate was 0.4 +/- 0.1 microSv/h at 2 m distance. Urine measurements yielded a cumulated 24 h excretion of 3.9 +/- 1.4% and 4.4 +/- 1.4% within 48 h, respectively, that is equivalent to 43 +/- 18 and 50 +/- 20 MBq of (90)Y, respectively. Family members received a radiation exposure of 40 +/- 14 microSv over seven days. CONCLUSION: During preparation and application of (90)Y-Zevalin appropriate radiation shielding is necessary. For family members as well as nursing staff no additional special radiation protection measures beyond those being common for other nuclear medicine procedures are necessary.

Allogeneic hematopoietic cell transplantation following conditioning with 90Y-ibritumomab-tiuxetan.

Radioimmunotherapy (RIT) of relapsed lymphoma is gaining increasing importance. Especially the commercially available anti-CD20 antibody 90Y-ibritumomab tiuxetan is currently under investigation in various trials including dose escalation and autologous hematopoietic progenitor cell support. It is not clear, however, whether the implementation of this radiolabeled antibody into another treatment option for relapsed or poor risk lymphoma patients-allogeneic hematopoietic cell transplantation-interferes with or delays successful engraftment. This study reports encouraging results with 2 relapsed lymphoma patients (1 transformed marginal zone lymphoma and 1 mantle cell lymphoma) who underwent allogeneic hematopoietic cell transplantation from HLA-matched donors. The conditioning regimen consisted of Rituximab 250 mg m(-2) on days -21 and -14, 0.4 mCi kg(-1) body weight 90Y-ibritumomab tiuxetan on day -14 and fludarabine (30 mg m(-2)) plus cyclophosphamide (500 mg m(-2)) on days -7 to -3. The data demonstrate that engraftment is fast and reliable with leukocytes >1 x 10(9) L(-1) on day 12 and platelets >50 x 10(9) L(-1) on day 10. Thus, the incorporation of radioimmunotherapy into allogeneic transplant protocols combines established modalities with proven anti-lymphoma activity and, hence, offers an attractive new therapeutic option for relapsed lymphoma patients.

Scintigraphic results in patients with lung transplants: a prospective comparative study.

AIM: We addressed the feasibility of scintigraphy in the postoperative monitoring of lung transplants. METHOD: 37 patients (22 women, 15 men, 37 +/- 15 years) in good clinical condition were examined after lung transplantation. Scintigraphic procedures for assessing ventilation (133Xe), perfusion (99mTc microspheres) and aerosol-inhalation (99mTc aerosol) were performed for all patients. The findings were compared with those of established diagnostic modalities. RESULTS: All lung transplants showed homogeneous ventilation but with a non-physiologic difference of over 20% between both pulmonary lobes in one-third of the cases. There was a difference between the impairement of perfusion and ventilation in the presence of an impaired Euler-Liljestrand reflex in 14/37 (38%) patients. Furthermore, bronchoscopy and aerosol-inhalation scans often did not correlate, e. g. a bronchoscopically evident stenosis was not necessarily associated with an increased activity, and vice versa. Although peripheral mucociliary clearance was preserved after transplantation, stasis in central airways resulted in significantly impaired global clearance. CONCLUSION: Ventilation and perfusion scintigraphy reveal in a significant number of lung recipients pathologic findings and therefore can be recommended for postoperative monitoring. From a clinical point of view aerosol-inhalation scintigraphy (clearance) is not of any additional value.

[Sentinel node biopsy in breast cancer]. / Wächterlymphknotenbiopsie beim Mammakarzinom.

The international consensus conference from St. Gallen concerning the treatment of early breast cancer concluded in 2003, that sentinel node biopsy was now accepted as method allowing axillary staging in breast cancer. This procedure may avoid complete lymph node dissection in appropriate cases. Since numerous questions associated with the technique are still not defined and the procedure itself is not yet standardized, the German Society of Senology defined the conditions for the routine clinical use of sentinel node biopsy in an interdisciplinary consensus meeting.

[Imaging techniques in rheumatology: scintigraphy in rheumatoid arthritis]. / Bildgebende Verfahren in der Rheumatologie: Szintigraphie bei rheumatoider Arthritis.

Bone scintigraphy is an important tool for staging and follow-up in patients with rheumatoid arthritis, and is part of the training for board certified physicians in nuclear medicine in Germany. Bone scintigraphy uses the accumulation of i.v. injected technetium-99m labeled phosphonates imaged with a gamma camera. Different phases can be defined: perfusion phase (0-60 s p. i.), blood pool phase (2-5 min p. i.), and bone (turnover) phase (2-5 h p. i.). The blood pool phase allowes judgement of inflammatory (soft tissue) components of joint disease ("arthritis"), the bone (turnover) phase of longer lasting bone processes ("arthrosis"). The technical details including documentation of the scintigraphic results are presented according to the procedure guidelines of the German Society of Nuclear Medicine (www.nuklearmedizin. de).

[Differentiation between vital heart muscle tissue and infarct scar using magnetocardiography]. / Differenzierung zwischen vitalem Herzmuskelgewebe und Infarktnarbe mit Hilfe der Magnetokardiographie.

Magnetocardiography provides touchless information about myocardial excitation propagation and repolarization. This evolving diagnostic technique has been used so far to risk-stratify patients in terms of sudden cardiac death and to detect myocardial ischemia. We evaluated its potential to assess myocardial viability in patients with coronary artery disease. Magnetocardiography was performed using a shielded prototype 49-channel LTS SQUID system. A specific algorithm was developed to calculate automatically a set of magnetocardiographic parameters. Regional myocardial viability was determined using 18F-labeled fluoro-2-deoxyglucose positron emission tomography. We found that magnetocardiography may contribute essentially to discriminate between viable myocardium and infarct scar.

Temporary shielding of hot spots in the drainage areas of cutaneous melanoma improves accuracy of lymphoscintigraphic sentinel lymph node diagnostics.

Detection of the "true" sentinel lymph nodes, permitting correct staging of regional lymph nodes, is essential for management and prognostic assessment in malignant melanoma. In this study, it was prospectively evaluated whether simple temporary shielding of hot spots in lymphatic drainage areas could improve the accuracy of sentinel lymph node diagnostics. In 100 consecutive malignant melanoma patients (45 women, 55 men; age 11-91 years), dynamic and static lymphoscintigraphy in various views was performed after strict intracutaneous application of technetium-99m nanocolloid (40-150 MBq; 0.05 ml/deposit) around the tumour (31 patients) or the biopsy scar (69 patients, safety distance 1 cm). The images were acquired with and without temporary lead shielding of the most prominent hot spots in the drainage area. In 33/100 patients, one or two additional sentinel lymph nodes that showed less tracer accumulation or were smaller (<1.5 cm) were detected after shielding. Four of these patients had metastases in the sentinel lymph nodes; the non-sentinel lymph nodes were tumour negative. In 3/100 patients, hot spots in the drainage area proved to be lymph vessels, lymph vessel intersections or lymph vessel ectasias after temporary shielding; hence, a node interpreted as a non-sentinel lymph node at first glance proved to be the real sentinel lymph node. In two of these patients, lymph node metastasis was histologically confirmed; the non-sentinel lymph nodes were tumour free. In 7/100 patients the exact course of lymph vessels could be mapped after shielding. In one of these patients, two additional sentinel lymph nodes (with metastasis) were detected. Overall, in 43/100 patients the temporary shielding yielded additional information, with sentinel lymph node metastases in 7%. In conclusion, when used in combination with dynamic acquisition in various views, temporary shielding of prominent hot spots in the drainage area of a malignant melanoma of the skin leads to an improvement in the accuracy of identification and localisation of sentinel lymph nodes by lymphoscintigraphy.

Bone marrow immunoscintigraphy in haematological patients with pancytopenia: preliminary results.

The aim of this study was to assess the clinical value of bone marrow immunoscintigraphy using the (99m)Tc labelled anti-NCA-95 antigranulocyte antibodies (AGAb) and of AGAb bone marrow uptake ratio (UR) in the initial diagnostic work-up of diseases with depression of the bone marrow. Twenty-four whole-body bone marrow scans were performed in 23 patients (11 women, 12 men; median age 46 years, range 17-74 years) 5 h after i.v. injection of 370 MBq of AGAb. The UR was calculated from the posterior view drawing an irregular region of interest around the sacroiliac and a background areas. The mean UR in pancytopenic patients was 2.3+/-1.5 (range 0.3-5.8), thus being significantly lower (P=0.45 x 10(-6)) than the mean UR in a control group of 50 patients (mean UR 7.3+/-2.3; range 4.4-12.6) obtained previously. Considering patient age, there was no overlap between UR of pancytopenic patients and the respective normal ranges. The bone marrow appearance on scans seemed to be characteristic for the different haematological diseases investigated. In six patients with myelofibrosis, bone marrow scans demonstrated diffusely decreased bone marrow activity and prominent splenic uptake, possibly related to extramedullary haematopoiesis. In aplastic anaemia, highly reduced and patchy marrow uptake was observed in four patients (five scans), in one of them persisting even after blood cell counts had recovered to the near-normal range. In another two patients with aplastic anaemia, diffusely decreased bone marrow uptake was obtained. In patients with myeloid leukaemia, bone marrow patterns were almost normal probably because the target antigen is often expressed on neoplastic myeloid cells, too. Bone marrow extension was a common finding in these patients. There is an obvious differentiation between haematological patients with pancytopenia and normal subjects by means of AGAb bone marrow uptake ratio. The distinct patterns of AGAb distribution may be indicative for particular haematological diseases.

Bone marrow scintigraphy with 99m Tc labelled monoclonal anti-NCA 90 Fab' fragment: a feasibility study and comparison of bone marrow uptake with 99m Tc labelled monoclonal anti-NCA 95 antigranulocyte antibody.

The aim of this retrospective study was to evaluate the usefulness of 99mTc labelled monoclonal anti-NCA 90 antigranulocyte antibody Fab' fragment (MN3 Fab') as a bone marrow imaging agent. One hundred and ten planar scans (88 patients) of the lumbar and sacroiliac regions as well as whole-body scans were performed after 1, 5 and 24 h. All the scans were evaluated visually and bone marrow uptake was determined semiquantitatively as count density ratio from sacroiliac-minus-background to background area. Results were compared to 50 age-matched patients with normal bone marrow scans obtained with the intact 99mTc labelled monoclonal anti-NCA 95 antigranulocyte antibody (BW 250/183) in a previous study. Seventy-three patients showed a physiological activity distribution in the central bone marrow. Ten patients showed a bone marrow extension, while in two patients central bone marrow depression was observed. Evaluation of the ribs, lower thoracic and upper lumbar spine was hampered by soft-tissue activity. Bone marrow uptake was 1.36+/-0.56 after 1 h, decreased thereafter and was significantly lower than that of BW 250/183 (P < 0.001). In conclusion, MN3 Fab' cannot be recommended for bone marrow scintigraphy, because relevant parts of the haemopoietically active bone marrow are not accessible to visual evaluation. A significant role of the semiquantitative evaluation of MN3 Fab' bone marrow uptake in patients with potential marrow depression seems unlikely.

Imaging of low-grade bone infection with a technetium-99m labelled monoclonal anti-NCA-90 Fab' fragment in patients with previous joint surgery.

Low-grade bone infection represents a serious clinical problem. Diagnostic options are often insufficient, yet the therapeutic implications of proven disease are important, especially in patients with prosthetic joint replacement. Technetium-99m labelled monoclonal anti-NCA-90 granulocyte antibody Fab' fragment (MN3 Fab') has been shown to be useful in bone and joint infection, but there are no data specifically referring to low-grade bone infection. We therefore analysed 38 scans in 30 consecutive patients (age range, 30-85 years; median age, 62 years) referred for suspected low-grade bone infection. There were 17 patients (21 scans) with total hip arthroplasty (THA), six with total knee arthroplasty (TKA), three who had undergone hip or knee surgery for trauma and five (seven scans) with resected hips and no endoprostheses (Girdlestone situations); one of these five patients had been investigated before with THA in situ and another prior to surgery for low-grade coxitis. There were no patients with rheumatoid arthritis as the underlying disease. Results were verified by means of bacteriological cultures, histopathological findings and/or follow-up and compared with the respective Zimmerli scores, which were used for clinical assessment of inflammatory activity. In one patient, the final diagnosis could not be established. One, 5 and 24 h after intravenous injection of up to 1.1 GBq of MN3 Fab', whole-body and planar scans were performed using a dual-head gamma camera. Scans were analysed visually and semiquantitatively adopting an arbitrary score ranging from 0 to 3. There were 13 true positive, 14 true negative and 10 false positive outcomes, yielding an overall sensitivity of 100%, an overall specificity of 58%, an accuracy of 73% and positive and negative predictive values of 57% and 100%, respectively. In patients with THA or TKA, accuracy was 81% and 80%, respectively, while it dropped to 43% in patients with Girdlestone situations owing to a high proportion of false positive findings (4/7) in this subgroup. Scintigraphic score was 1 in all of the false positive and in 11/13 true positive findings. The two remaining true positive findings displayed scintigraphic scores of 2 and 3, respectively. Scintigraphic and Zimmerli scores were loosely correlated (Spearman rho=0.38, P<0.05). Infection was excluded in 22/24 investigations with Zimmerli scores of <6. In this group, there were 13 scintigraphically true negative, nine false positive outcomes, and just two true positive outcomes. In 11/12 investigations with Zimmerli scores of 6 or 7, infection was verified and scintigraphic outcome was accordingly true positive, while the remaining patient was true negative. In conclusion, MN3 Fab' scintigraphy proved to be highly sensitive but not specific in diagnosing low-grade infections of the hip and knee regions in patients with previous joint surgery. The method seems reliable in excluding but not in proving the presence of infection. MN3 Fab' scintigraphy should not be applied in patients with Girdlestone situations. Assessment of infection using the Zimmerli score was more reliable than MN3 Fab' scintigraphy in this group of patients without rheumatoid arthritis as the underlying disease. Considering results from the literature concerning leucocyte scintigraphy, MN3 Fab' scintigraphy may be clinically useful in evaluating low-grade bone infection in THA and TKA patients with Zimmerli scores above 5 and concomitant rheumatoid arthritis or other inflammatory diseases.

Nonspecific bowel activity in imaging inflammation with Tc-99m labelled monoclonal anti-NCA-90 Fab' fragment MN3.

AIM: Since the Tc-99m labelled monoclonal anti-NCA 90 granulocyte antibody Fab' fragment MN3 (MN3 Fab') might be of interest for imaging abdominal inflammation which could be hampered by nonspecific bowel activity, we prospectively investigated the appearance of bowel activity in MN3 Fab' imaging. METHODS: Eighty consecutive patients (age range 12-85 years) referred for suspected nonabdominal, mostly musculoskeletal infection, were included. Abdominal inflammation was excluded clinically and there were no signs of inflammatory bowel disease in the patients' histories. One, 5, and 24 hours after intravenous injection of up to 1.1 GBq of MN3 Fab' planar images of the abdomen were performed. Bowel activity was graded visually using a 5-point scale. RESULTS: The one (N = 80), 5 (N = 79), and 24 (N = 52) hour images revealed 46 (10%), 162 (34%), and 173 (55%) accumulating bowel segments, respectively, in 37 (46%), 69 (87%), and 52 (100%) patients. The mean intensity score per accumulating segment was 1.1, 1.8 and 2.7 (p = 0), respectively. Relative frequencies of appearance of the small intestine were 38%, 57%, and 21%, ileocaecal region 6%, 53%, and 48%, ascending colon 5%, 67%, and 89%, transverse colon 1%, 9%, and 69%, descending colon 8%, 15%, and 67%, and rectosigmoid 0%, 4%, and 38%, respectively. Follow-up investigations in 13 patients revealed diverging uptake patterns. CONCLUSION: Nonspecific bowel activity is often present in the early and almost always and more intense, in the delayed images. Early imaging at one hour after administration seems feasible, but a loss in sensitivity has to be considered. Thus, nonspecific bowel activity can be anticipated to be a pitfall in imaging abdominal inflammation with MN3 Fab'.

Extraction of long-chain fatty acids in isolated rat heart during acute low-flow ischemia.

UNLABELLED: Although beta-oxidation of fatty acids is suppressed rapidly during ischemia, the behavior of fatty acid extraction at different flow rates is incompletely understood. This study assessed the relationship between flow and extraction of (123)I-iodophenylpentadecanoic acid (IPPA) in the isolated heart model, especially at low flow. METHODS: Isolated hearts from male Wistar rats (n = 15) were subjected to retrograde perfusion with constant flow (Krebs Henseleit solution containing 10 mmol/L glucose). A latex balloon in the left ventricle allowed isovolumetric contractions and ventricular pressure measurements. The extraction of (123)I-IPPA was assessed with the indicator dilution technique and (99m)Tc-albumin as the intravascular reference. The flow was either increased from the control flow (8 mL/min) until 300% or reduced until 10%. (123)I-IPPA extraction was measured three times before and 10 min after flow alteration. The tracer uptake was estimated from the product of net extraction and flow. RESULTS: The mean (123)I-IPPA extraction at the control flow (third measurement) was 51.6% +/- 2.8%. Between flow rates of approximately 25% and 300%, (123)I-IPPA extraction increased exponentially at decreasing flow rates. At flow rates < or =25% of the control flow, (123)I-IPPA extraction was exponentially higher than predicted. (123)I-IPPA uptake and flow changed largely in parallel. During low flow, the rate-pressure product showed the expected decline (perfusion-contraction matching). CONCLUSION: The extraction of (123)I-IPPA is preserved and slightly increased (relative to flow) during acute low-flow ischemia.

Endoscopic sentinel node detection with a gamma probe combined with minimally invasive axillary lymph node dissection: a preliminary study.

OBJECTIVE: To investigate the efficacy of videoendoscopic axillary lymph node dissection combined with endoscopic sentinel node detection by gamma probe and preoperative sentinel node imaging. DESIGN: Open study. SETTING: University hospital, Germany. SUBJECTS: Four patients with breast cancer. INTERVENTION: Injection of 99mTc-nanocolloid around the tumour. RESULTS: In three patients axillary sentinel nodes were detected both before and after operation. In the remaining one it was not found. In two patients the minimally invasive approach had to be converted to conventional open surgery because of anatomical restrictions. CONCLUSION: We describe a new approach that uses a minimally invasive technique and endoscopic radioguided sentinel node biopsy in patients with breast cancer. The results of this preliminary study warrant further investigation.

Combined thallium-201 and dynamic iodine-123 iodophenylpentadecanoic acid single-photon emission computed tomography in patients after acute myocardial infarction with effective reperfusion.

BACKGROUND: Considerable derangements of energy metabolism are to be expected during ischemia and reperfusion. In ischemic myocardium, the oxidative degradation of carbohydrates is shifted toward the anaerobic production of lactate and the oxidation of fatty acids is suppressed. HYPOTHESIS: The aim of this study was to examine the uptake and metabolism of iodine-123 (123I) iodophenylpentadecanoic acid (IPPA) in stunned myocardium. METHODS: In 15 patients, SPECT with 201Tl and 123I IPPA as well as echocardiography with low-dose dobutamine stimulation were performed 12 +/- 5 days after myocardial infarction with reperfusion. Follow-up echocardiography was carried out 24 +/- 8 days later for documentation of functional improvement. Uptake of 201Tl and 123I IPPA were obtained in five left ventricular segments, and dynamic SPECT imaging was used for calculation of the fast and the slow components of the biexponential myocardial 123I IPPA clearance. RESULTS: Wall motion improved in 14 of 26 dysfunctional segments (54%). Stunned segments were characterized by a reduced 123I IPPA extraction, a shorter half-life of the fast, and a longer half-life of the slow clearance component. All parameters of the combined 201Tl/123I IPPA study predicted functional recovery with similar accuracies (area under the receiver operator characteristic curves between 0.68 and 0.76; p = NS). Analysis of 201Tl uptake alone could not predict functional recovery in this study. CONCLUSIONS: Stunned myocardium is characterized by a disturbance of fatty acid metabolism. For prediction of functional improvement, 123I IPPA imaging added significant diagnostic information.