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'.

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.

Fuzzy-stochastic functor machine for general humanoid-robot dynamics.

In this paper the fuzzy-stochastic-Hamiltonian functor-machine is proposed as a general model for the humanoid-robot dynamics, including all necessary degrees of freedom to match the "realistic" human-like motion. Starting with the continual-sequential generalization of the standard state equation for the linear MIMO-systems, the "meta-cybernetic" model of the "functor-machine" is developed as a three-stage nonlinear description of humanoid dynamics: (1) dissipative, muscle-driven Hamiltonian dynamics, (2) stochastic fluctuations and discrete jumps, and (3) fuzzy inputs, parameters and initial conditions. An example of symmetrical three-dimensional (3-D) load-lifting is used to illustrate all the phases in developing the functor-machine model.

Diagnosis and management of left ventricular assist device valve-endocarditis: LVAD valve replacement.

A 57-year-old man who has been wearing a Novacor N100 left ventricular assist device (LVAD) for more than 3 years suffered from LVAD endocarditis. Only by immunoscintigraphic methods was it possible to localize the septic focus. After successful exchange of in- and outflow tract valves, the infection was eradicated. Microscopic investigation confirmed the scintigraphic findings: Gram-positive bacteria were found. The valves showed no gross degenerative lesions after more than 1,100 days of implantation. The patient is now doing well.

Regional cerebral glucose metabolism in healthy volunteers determined by fluordeoxyglucose positron emission tomography: appearance and variance in the transaxial, coronal, and sagittal planes.

PURPOSE: In this study, the contribution of the transaxial, coronal, and sagittal planes in evaluations of regional cerebral glucose metabolism was investigated in healthy volunteers as determined by fluorine-18-labeled 2-deoxy-2-fluoro-D-glucose (FDG) and high-resolution positron emission tomography (PET). METHODS: One hundred twenty-seven healthy right-handed volunteers were injected with 4.2 MBq/kg (0.11 mCi) body weight FDG and imaged in a PENN PET H 240 scanner. Images were corrected for scatter and random coincidences and reconstructed in all three planes into 6- to 8-mm-thick slices. The reconstructed images were corrected for attenuation using the Chang algorithm. The transverse, coronal, and sagittal images were read independently of each other using a qualitative scale in which 1 = equal to, 2 = mildly, 3 = moderately, and 4 = markedly less than the area with the highest glucose metabolism in the respective plane. RESULTS: The areas with the highest glucose metabolisms were the posterior cingulate gyri with mean scores of 1.1 to 1.2, thalami (1.2 to 1.3), basal ganglia (1.5 to 1.9), and visual cortex (1.6). The lowest values were found in the occipital cortex (2.7 to 2.8) and the cerebellum (2.3 to 2.4). Whereas reliable analysis of the mesial temporal aspects was not feasible in the sagittal plane, the anterior poles of the temporal and frontal lobes could not be evaluated in the coronal or the inferior temporal areas in the transaxial slices. In all three planes, regional glucose metabolism was less in the lateral temporal areas on the left than on the right (P < 0.001). The consistency of readings as measured in terms of coefficients of variation was greatest in the coronal plane for the caudates and posterior cingulate gyri, in the transaxial plane for the lateral temporal regions, and in the sagittal plane for the visual cortex. Age-dependent decreases in regional glucose metabolism in the inferior and lateral frontal regions and the parietal lobes were found in all three planes. CONCLUSIONS: All three projection planes must be used for a comprehensive qualitative evaluation of the regional glucose metabolism of the brain.

Classification of the lymphatic drainage status of a primary tumour: a proposal.

AIM: Creation of a classification of the lymphatic drainage status of a primary tumour. It shall enable comparison of different approaches, standardization and quality control. METHODS: Identification and topographic localization of the sentinel node(s) using lymphatic radionuclide gamma camera imaging and/or gamma probe detection and/or vital dye mapping. RESULTS: A classification comprising four classes (D-Class I-IV) and distinct subclasses (A-E) proved to be simply to be learned and applicable as well as reliably reproducible. It is based on the number of sentinel lymph nodes and their locations and can be combined with the pathological and molecular biological lymph node status. D-classes/subclasses obtained in 420 patients with malignant melanoma of the skin are presented. CONCLUSIONS: The classification is applicable to different approaches. Its diagnostic, therapeutic and prognostic value should be studied prospectively in those primary tumours which preferably metastasis via their draining lymphatic vessels.

Intraindividual Comparison of F-18-Fluorodeoxyglucose and Tc-99m-Tetrofosmin in Planar Scintimammography and SPECT.

Since the comparative value of several nuclear medicine investigations for breast cancer has not been established, the rationale of this study was to examine the diagnostic performances of F-18-fluorodeoxyglucose (FDG) and Tc-99m-tetrofosmin both in single photon emission computed tomography (SPECT) and planar technique in an intraindividual comparative study.A total of 54 patients with suspected breast cancer (48 malignant and 9 benign lesions) was investigated by planar and SPECT imaging with both FDG and tetrofosmin within the last preoperative week. Pathohistological confirmation of the diagnosis was obtained in all patients.2 cm 81%/67%, 92%/67%, 75%/50%, and 75%/100%. Sensitivity was higher with FDG SPECT than with the other imaging modalities and significantly lower for tumors

Dominant beta-thalassaemia: a highly unstable haemoglobin is caused by a novel 6 bp deletion of the beta-globin gene.

Beta-thalassaemia is inherited as an autosomal recessive trait in most families. Particular interest has recently been focused on the molecular pathology of the rare forms with a dominant mode of inheritance. The index patient and her mother, who are described in this report, displayed typical clinical and haematological features of beta-thalassaemia intermedia with significant ineffective erythropoiesis and additional peripheral haemolysis. Molecular analysis demonstrated a heterozygous genotype for a novel 6 bp (TGGTCT) deletion of the beta-globin gene involving codons 33-35. This deletion results in the removal of two valine residues from the beta-globin chain at position 33/34 (B15/B16) and the substitution of the tyrosine residue at position 35 (C1) by an aspartic acid (beta 33-35 [B15-C1] Val-Val-Tyr-->0-0-Asp). According to the index patient's place of birth, this abnormal haemoglobin has been termed Hb Dresden. The stability of the variant and the normal beta-globin chains were similar during the incubation period of in vitro globin chain synthesis analysis. However, Hb Dresden is exquisitely unstable and cannot be detected in the peripheral blood by haemoglobin electrophoresis, high-performance liquid chromatography (HPLC) or isoelectric focusing. This instability can be explained by the vital structural role of the three affected amino acids that, in normal haemoglobin, establish a total of nine intermolecular bonds (five hydrophobic and four polar) at both the alpha1beta1 (alpha2beta2) and the alpha1beta2 (alpha2beta1) interface.

Nuclear medicine imaging of endocarditis.

Infective endocarditis is a serious disease which requires early diagnosis and adequate therapy. Echocardiography plays a key role in diagnosis and follow-up. Subacute infective endocarditis, however, is often difficult to prove echocardiographically due to its more subtle morphological changes. Also, echocardiography cannot reliably differentiate florid vegetations from residual structural changes of the affected valves in cured patients. Therefore, scintigraphy of infection and inflammation, a functional imaging procedure, has been investigated as a complementary tool in diagnosis and follow-up of infective endocarditis. So far, results obtained with Gallium-67 scintigraphy are not convincing, although an improvement by using modern acquisition techniques seems possible. Scintigraphy with Indium-111 labelled leukocytes has an unacceptably low sensitivity, which is probably due to the small number of cells involved and unfavourable imaging characteristics of 111In-Technetium-99m labelled leukocytes have been investigated in few patients, so final judgement is not yet possible. SPECT imaging might enhance the detectability of diseased heart valves. Immunoscintigraphy with the 99mTc labelled antigranulocyte antibody in SPECT technique is complementary to echocardiography and seems to assess the floridity of the underlying inflammatory process. The combined use of both imaging modalities allows detection of virtually all cases of subacute infective endocarditis. SPECT immunoscintigraphy with the antigranulocyte antibody seems useful in doubtful cases of infective endocarditis, especially, if echocardiography is non-diagnostic and valve pathology pre-existing. The method may be used for follow-up and monitoring antibiotic therapy.

[3-phase bone scintigraphy of microsurgically attached bone transplants as early graft survival assessment]. / Die Dreiphasen-Knochenszintigraphie mikrochirurgisch angeschlossener Knochentransplantate als früher Vitalitätsnachweis.

Vascularized bone grafts do not allow direct graft monitoring during the early postoperative period. The first two weeks are critical for the blood supply and viability of the graft. Three-phase bone scintigraphy, performed between the 7th and 14th postoperative day, was valuable in predicting the survival of vascularized bone grafts. It is a simple and safe method for the evaluation of blood supply of both the graft and the graft-surrounding tissue. Clinical data, obtained from studying 17 patients,/led to the conclusion that three-phase bone scintigraphy plays an important role in the process of decision-making on surgical reexploration.

Clinical value of immunoscintigraphy in patients with fever of unknown origin.

UNLABELLED: The aim of our study was to evaluate the clinical value of immunoscintigraphy with the monoclonal antibody 99mTc-BW 250/183 in patients with fever of unknown origin (FUO). The antibody BW 250/183 is an immunoglobulin G1 subtype that binds to the antigen NCA-95, which is expressed on the cell membrane surface of granulocytes. METHODS: We studied 51 patients who were referred with the diagnosis of FUO. Thirty-five percent of the patients suffered from infection, 17% had autoimmune diseases, 14% had neoplasms and 8% had other diseases. The remaining 28% of the patients did not have a diagnosis. Planar imaging was performed in all patients, and 19 patients underwent SPECT. In our analysis, both cold and hot spots were considered diagnostic. RESULTS: Pyogenic infections were visualized correctly in 13 foci. The diagnosis of endocarditis (n = 4) could be determined only by SPECT. False-negative results were found in 4 patients and false-positive uptake was seen in 2 patients. No false-positive uptake or cold spots in the central bone marrow were found in patients with viral, granulomatous and autoimmune diseases or in those patients in whom no FUO cause was found in a 6-mo follow-up. In these patients, a negative scan did not change their diagnostic work-up. Cold spots in the central bone marrow were correctly interpreted in 5 of 6 patients. Sensitivity in detecting pyogenic foci was 73% and specificity was 97%. Positive and negative predictive values were 93% and 87%, respectively. Including areas of decreased uptake in the analysis, sensitivity for detecting an underlying inflammatory or malignant process for FUO was 81 % and specificity was 87%. Positive and negative predictive values were 81% and 87%, respectively. CONCLUSION: Immunoscintigraphy with 99mTc-BW 250/183 in patients with FUO has clinical potential for the diagnosis and exclusion of pyogenic causes of FUO. Metastatic malignant disease and high-grade spondylodiskitis could be diagnosed early in a diagnostic work-up by a characteristic cold spot pattern in the bone marrow. SPECT is indispensible for scintigraphic imaging of endocarditis.

[Positron emission tomography (PET) in diagnosis of breast carcinoma]. / Die Positronen-Emissions-Tomographie (PET) in der Diagnostik des Mammakarzinoms.

Position emission tomography (PET) offers new opportunities in the non-invasive diagnosis and therapy monitoring of breast cancer. So far, PET with the glucose analogue fluorodeoxyglucose is investigated best, especially in diagnosing the primary tumour and in staging axillary lymph nodes. The validity of the method in staging distant metastases and monitoring therapy is also being investigated. At the moment, few data is available on PET with C-11-methionin as well as on PET with more specific radiopharmaceuticals like I-124-labelled monoclonal antibodies and F-18-labelled estrogen receptor ligands. This short review presents the state of the art of PET in the diagnostics and therapy monitoring of breast cancer.

Immunoscintigraphy of the bone marrow: normal uptake values of technetium-99m-labeled monoclonal antigranulocyte antibodies.

UNLABELLED: The aim of our study was to determine the normal range of the 99mTc-labeled anti-NCA 95 antigranulocyte antibody (AGAb) uptake in the bone marrow using the sacroiliac-to-background uptake ratio in the posterior view. METHODS: We made 169 planar bone marrow scans on 162 patients who were each injected with 555 MBq AGAb. Fifty patients with the diagnosis of infection/pyrexia of unknown origin (PUO) and with completely normal bone marrow scintigraphy were defined as the normal group. Uptake ratios were calculated drawing irregular regions of interest around the sacroiliac and a background area, respectively. RESULTS: The normal group revealed a mean uptake ratio of 7.3 +/- 2.3 (range 4.4-12.6). Similar uptake ratios were obtained in patients with the primary diagnosis of infection/PUO and bone marrow extension (7.4 +/- 2.2, range 4.2-11.7), suggesting that the bone marrow reacts on infection primarily by extension into the periphery, without any significant increase of the activity of the central hemopoietic/granulopoietic bone marrow. Mean uptake ratios also were not significantly different in patients with normal bone marrow scintigraphy and the primary diagnosis of solid malignant tumors, lymphomas and plasmacytomas, and in patients with focal lesions visible on bone marrow scintigraphy (soft tissue inflammation or cold lesions in the bone marrow but with normal sacroiliac regions). Mean uptake ratios in the normal group were significantly age related, amounting to 8.5 +/- 1.8, 7.5 +/- 1.9 and 6.1 +/- 2.0 in patients younger than 40 yr, between 40 and 59 yr, and 60 yr or older, respectively (p = 0.0025). The method revealed good inter- and intraobserver agreement with correlation coefficients of about r = 0.90 and r = 0.95, respectively. Inter- and intraobserver coefficients of variation were 6.6% and 4.6%, respectively. CONCLUSION: Determination of the bone marrow uptake ratio is simple and reproducible. The normal values established in this study were age dependent, which has to be considered when interpreting bone marrow uptake ratios. The presence of infection/PUO, solid malignant tumors, lymphomas and plasmacytomas does not seem to alter the AGAb uptake ratio significantly. The most important application of the quantitative analysis of bone marrow scintigraphy could be the diagnosis and follow-up of diseases with depression of the central hemopoietic activity.

Somatostatin receptor scintigraphy in the staging of lymphomas.

In this prospective study we evaluated the somatostatin receptor scintigraphy in the initial staging of 19 patients suffering from Hodgkin's (HD) and non-Hodgkin's lymphomas (NHL) and in the restaging of 16 patients. Scintigraphy was compared to the results of the methods applied for adequate staging of lymphoma patients in the large multicentre trials. Planar imaging and SPECT was performed after intravenous injection of 110 or 220 MBq of 111In-pentetreotide. The patient-based analysis yielded an overall sensitivity of 88%, contrasting lesion-based sensitivities of 57%, 35%, and 43% in HD, low-grade NHL and high-grade NHL, respectively. The best results were obtained in the head-and-neck region and the worst in the abdomen (sensitivities of 61% and 24%, respectively). Bone marrow infiltration was visible in 1/12 cases only. There was no significant difference between the outcomes of patients in the initial staging and restaging and no influence of the amount of injected radiopharmaceutical on the results. In terms of the Ann-Arbor classification, 10/35 patients were concordant whereas 22 were understaged and 3 overstaged scintigraphically. In conclusion, somatostatin receptor scintigraphy is not useful in the initial staging or restaging of malignant lymphomas, especially NHL, due to low lesion detection rates most probably because of low receptor densities. In addition, intraindividual heterogeneity of somatostatin receptor expression has to be considered.