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The value of Tc-99m HEDP bone scintigraphy as a means of detecting uremic pulmonary calcification was studied in 30 chronic dialysis patients. A high incidence of currently recognized predisposing factors for metastatic calcification was found and calcification was recorded at other sites. Scintigraphy was performed after reducing background activity by hemodialysis to levels found in normals. From chest images and chest-to-spine activity ratios, evidence of pulmonary calcification could be obtained in only one patient, and subsequent histologic examination revealed extensive calcification. High chest-to-spine activity ratios suggested increased pulmonary radionuclide uptake in several other patients, but these findings were not conclusive. These results indicate that uremic pulmonary calcification--which, according to autopsy studies, develops in about 60-75% of dialysis patients--cannot be detected with bone-seeking radiopharmaceuticals, unless the calcification is severe. This is probably due to the unusual crystalline and chemical composition of uremic pulmonary calcification.

The purpose of this study was to determine the reliability of the measured left ventricular ejection fraction (LVEF) and wall motion analysis by the recently introduced quantitative electrocardiographically (ECG)-gated myocardial perfusion single-photon emission computed myocardial tomography technique (gated SPECT) (QGS).We compared technetium-99 m tetrofosmin gated SPECT imaging and contrast ventriculography in the assessment of global and regional left ventricular function in 74 patients with undiagnosed chest pain of whom 27 sustained a previous myocardial infarction.Linear regression analysis demonstrated that gated SPECT determined LVEF correlated well with LVEF determined from contrast ventriculography (y = 0.95x + 1.9, r2 = 0.84, p0.0001). Bland-Altman plot analysis showed no systematic difference between the two sets of values derived from the two imaging approaches over a wide range of LVEF values. Exact agreement of segmental wall motion scores was 460 of 518 (89%) segments with a kappa value of 0.76 (p0.0001).We conclude that gated SPECT imaging is an accurate and reliable clinical tool to accurately measure global and regional left ventricular function.

Bone scintigraphy continues to be one of the most commonly performed procedures in nuclear medicine. The radionuclide bone scan remains an excellent modality to detect metastatic disease in patients suffering from primary malignancies. This article reviews a number of aspects of bone scintigraphy such as bone physiology, radiopharmaceuticals and uptake mechanisms. As 99mTc labelled bis(di)phosphonates are the most frequently used this article is centred around these imaging agents. In addition to diagnostic bone scintigraphy the use of various bone seeking agents has been extended to the palliative treatment of bone metastases. In this context the radiobiological characteristics of various radionuclides as 89Sr, 32p, 153Sm, 186Re and 117Sn is elucidated. In addition, the clinical efficacy for pain killing of these radionuclides is elucidated on the basis of the radiation properties of these agents. It is concluded that 89Sr and 186Re are presently the radionuclides of choice. The latter agent has a slight advantage as its imaging photons enable individual dosimetry, resulting in an optimosed application scheme.

The presence of a left bundle branch block (LBBB) pattern on the electrocardiogram may frequently lead to perfusion defects in the septum not necessarily due to ischemic heart disease, but probably due to abnormal septal wall motion. The introduction of gated single photon emission computed tomography (SPECT) allows the evaluation of myocardial perfusion and function in one study. Accordingly, we analysed perfusion and function and the relation between perfusion and regional function in the septal region in patients with a LBBB without evidence of a previously sustained myocardial infarction.We selected 37 patients with a LBBB without a history of a previous myocardial infarction, which was confirmed by echocardiography and/or coronary angiography. All patients underwent technetium-99m tetrofosmin gated SPECT myocardial imaging. Twelve control patients with a low likelihood of coronary artery disease and a normal technetium-99m tetrofosmin gated SPECT myocardial perfusion scintigram were selected as a reference population. The left ventricle (LV) was divided into 18 segments, which were scored for perfusion and function (wall motion and wall thickening) on a 4-point scale.The average LV end-diastolic volume was higher and the average LV ejection fraction was lower in patients with LBBB as compared to controls (142+/-90 vs. 81+/-18 ml, and 48+/-19 vs 62+/-7%, p=0.03 and p=0.02, respectively). Not only in the septum, but also in the other segments, reduced myocardial perfusion and abnormal wall motion/wall thickening was observed in the patients with LBBB (p0.0001 vs controls). Patients with LBBB showed no correlation between perfusion and function in the septum, and between perfusion in septum and global LV function (r=0.21, p=0.2; r=0.10, p=0.6, respectively). Conversely, a good correlation was found between perfusion and function, either regional or global, in the remote segments (both r=0.79, p0.0001).We conclude that patients with LBBB without a previous myocardial infarction show cardiomyopathic changes with perfusion and wall motion abnormalities, involving the entire left ventricle. The severity of diminished septal perfusion is not directly associated with the severity of septal wall motion abnormalities or global LV function. However, in the myocardial segments remote from the septum, reduced perfusion is closely associated with functional abnormalities.

Positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) is considered to be a very useful adjunct to anatomic imaging techniques and is now primarily used for oncological indications. These indications include diagnosis, staging, and therapy monitoring. In this review, we discuss the articles in which FDG-PET is clinically used for monitoring therapy in lung and colorectal tumours, head and neck cancer, sarcoma, and hepatocellular carcinoma. It is found that the amount of FDG uptake strongly correlates with response to therapy: a decrease in FDG uptake after therapy indicates a positive response to therapy. However, this conclusion is based on small numbers of patients, whereas the exact response mechanism is still unknown. Moreover, in these case series, the interval between tumour therapy and FDG-PET, as well as the method of quantification, SUV or tumour-to-non-tumour ratios, differ per study. Finally, dynamic imaging is a recommended technique by some authors, but it is not a standard technique in clinical practice to evaluate tumour therapy. Therefore, further study is required which has to deal with these major issues before it is possible to draw definite conclusions.

This study compared the possibilities and limitations of 99mTc-labeled synthetic peptides derived from two human antimicrobial peptides, namely, ubiquicidin (UBI) and lactoferrin (hLF), for the scintigraphic detection of bacterial and fungal infections in mice and rabbits. The rationale of our approach was that selected peptides accumulate in infected areas but not in sterile inflammatory lesions, because they bind preferentially to microorganisms. 99mTc-labeled human neutrophil peptides (defensins), ciprofloxacin, and human polyclonal IgG were included as control agents.99mTc-labeled peptides and control agents were injected intravenously into animals that had been injected intramuscularly 18 h earlier with multidrug-resistant Staphylococcus aureus, Klebsiella pneumoniae, or fluconazole-resistant Candida albicans. Sterile inflammatory sites were induced by the injection of heat-killed microorganisms or lipopolysaccharide (LPS) into the thigh muscle. Up to 4 h after injection, the accumulation of 99mTc-labeled compounds in the infected/inflamed thigh muscles was determined using scintigraphic techniques and radioactivity counts in dissected tissues.Scintigraphy revealed that 99mTc-labeled peptides UBI 29-41, UBI 18-35, UBI 31-38, hLF 1-11, and defensins, which showed preferential in vitro binding to microorganisms in a former study, accumulated at a significantly higher rate (P0.01) in bacterial and C. albicans infections in mice and rabbits than in inflamed tissues induced by heat-killed microorganisms or by LPS. No significant difference in the accumulation of 99mTc-labeled ciprofloxacin was observed between infected and sterile inflamed thigh muscles in mice.99mTc-labeled antimicrobial peptides UBI 29-41, UBI 18-35, UBI 31-38, hLF 1-11, and defensins accumulate significantly in tissues infected with gram-positive and gram-negative bacteria and C. albicans. Significantly lower (P0.01) accumulation of these peptides occurs in sterile inflamed tissues. These data indicate that the peptides preferentially tag microorganisms at the site of infection, which is in agreement with their preferential binding to the microorganisms in vitro and in vivo. 99mTc-labeled ciprofloxacin does not distinguish between infections and sterile inflammatory lesions, which implies that its specificity for the detection of bacterial infections is not warranted.

Since 1942, therapy with radioiodine (Na131I) has gained a major role in the treatment of benign thyroid disorders, notably hyperthyroidism caused by Graves' disease or toxic multinodular goiter. The very large series of patients treated so far offer the opportunity for an assessment of both benign and malignant side effects. Hyperthyroidism is sometimes observed after radioiodine therapy due to radiation induced thyroid hormone or by an immunological mechanism. Despite the numerous attempts to design dosage schedules aiming at euthyroidism, hypothyroidism occurs in the majority of patients throughout life. Transient hypothyroidism may be observed within the first year after therapy and is caused by an immunological mechanism. Radioiodine therapy in Graves' disease may induce or worsen ophthalmopathy, which can be prevented by steroids effectively. Hypoparathyroidism and hyperparathyroidism have been reported after radioiodine therapy but probably do not exceed the normal incidence. Sialitis is commonly observed but mostly in patients treated with radioiodine for thyroid cancer. There are no indications for induction of genetic abnormalities after radioiodine therapy although no definite conclusion can be reached. Much attention has been paid to malignant disease. In very large series, no effects of radioiodine therapy on survival have been observed. Some studies report an increased relative risk for certain types of cancer (notably thyroid cancer, stomach cancer, bladder and kidney cancer or hematological malignancies). However, these observations were not confirmed by other large studies, so that no definite conclusion with respect to risk for certain types of malignant disease can be drawn. However, radioiodine therapy for benign thyroid disorders has generally been considered safe and without major side effects, hypothyroidism being the most frequent one.

Organ transplantation is now an accepted method of therapy for treating patients with end stage failure of kidneys, liver, heart or lung. Nuclear Medicine may provide functional data and semi-quantitative parameters. However, one serious factor that hampers the use of nuclear medicine procedures in transplant patients is the general clinical concern about radiation exposure to the patient. This leads us to discuss the effective doses and radiation dosimetry associated with radionuclide procedures used in the management and follow-up of transplant patients. A simple way to place the risk associated with Nuclear Medicine studies in an appropriate context is to compare the dose with that received from a more familiar source of exposure such as from a diagnostic X-ray procedure. The radiation dose for the different radiopharmaceuticals used to study transplant organ function ranges between 0.1 and 5.3 mSv which is comparable to X-ray procedures with the exception of 201Tl and 111In-antimyosin. Thus Nuclear Medicine studies do not bear a higher radiation risk than the often used X-ray studies in transplant patients.

This study was undertaken to evaluate whether 99mTc-labeled human neutrophil peptide (HNP)-1 can be used as a tracer for rapid visualization of bacterial infections.Mice were injected intramuscularly with 1 million Staphylococcus aureus or Klebsiella pneumoniae organisms and 5 min later were injected intravenously with 0.4 microg (0.8 MBq) 99mTc-HNP-1. At various intervals, detailed information about clearance and accumulation of this tracer at sites of infection and in various organs was obtained by scintigraphy. 99mTc-labeled immunoglobulin G (IgG), an established marker of infection and inflammation, was used for comparison.After injection into S. aureus- or K. pneumoniae-injected mice, 99mTC-HNP-1 was rapidly removed from the circulation, mainly through the kidneys and bladder, with half-lives of 170 and 55 min, respectively. Similar half-lives were observed for 99mTc-IgG in these animals. Visualization of foci with S. aureus or K. pneumoniae, as indicated by a ratio of 1.3 or higher between the targeted thigh muscle (containing bacteria) and the nontargeted (contralateral) thigh muscle (T/NT), was already achieved 5 min after injection of 99mTc-HNP-1. Similar T/NTs for 99mTc-IgG were obtained 4 h after injection of the tracer, indicating that imaging of foci of bacteria with 99mTc-HNP-1 is much faster than with 99mTc-IgG. To obtain insight into factors that contribute to accumulation of 99mTc-HNP-1 at sites of infection, the binding of this tracer to bacteria and leukocytes was assessed using a peritoneal infection model. Binding of 99mTC-HNP-1 to bacteria was approximately 1000 times higher than binding to leukocytes. Although the number of bacteria in the peritoneum was 1000-fold lower than the number of leukocytes, a significant correlation between binding of 99mTc-HNP-1 to bacteria on the one hand and accumulation of tracer on the other was still found, in contrast to 99mTc-IgG.99mTc-HNP-1 allows rapid visualization of bacterial infections. Binding of this tracer to bacteria most likely contributes significantly to the accumulation of 99mTc-HNP-1 at sites of infection.

In patients with limited disease SCLC, the overall survival is still poor. Therefore, a retrospective study was performed involving 48 patients with limited disease SCLC to select a parameter which can identify prognostic subgroups at the time of diagnosis.Follow-up ranged from 3 to 96 months, during which period 38 patients died. Based on clinical outcome, patients were classified into 3 groups: complete remission (CR) (n = 16), local recurrence (LOC) (n = 7) and distant recurrence (DIS) (n = 25). Age, gender and pretreatment biochemical parameters were correlated with clinical outcome and survival. For survival 70 patients staged as having extensive disease (ED) served as a control group.No differences in survival were found in patients with LOC (14% 2 year survival) and DIS (16% 2-year survival) (p = 0.67). Patients achieving a complete remission had a significantly better survival (75% two-year survival). LDH was found to be the only significant correlate of both tumor progression and survival. All patients with pretreatment LDH levels240 U/L (n = 13) had tumor recurrence. The survival rate of patients with LDH levels, 240 U/L (41% 2-year survival) was much better than that of patients with LDH levels240 U/L 8% 2-year survival) (p = 0.0001). No significant difference in survival (p = 0.33) was found between patients with LD and LDH240 U/L and patients with ED and LDH400 U/L. Patients with ED and LDH values400 U/L showed the poorest outcome.LDH may be used for the identification of prognostic subgroups in SCLC. Patients showing pretreatment LDH levels240 U/L have an extremely high risk of tumor recurrence, while their survival is poor and comparable to that of patients staged as having extensive disease and LDH values400 U/L.

A head-to-head comparison between 99mTc-sestamibi SPECT and planar myocardial imaging using dipyridamole low-level exercise stress was performed for the assessment of coronary artery disease (CAD) and for the impact on patient management in 78 patients (pts) who underwent coronary arteriography. Overall sensitivity and specificity for detection of CAD were 82% and 82% for SPECT, and 78% and 73% for planar imaging, respectively (both NS). Compared to planar imaging the sensitivity of SPECT imaging was significantly higher for detecting left anterior descending (p = 0.02) and left circumflex (p = 0.03) coronary artery disease. In predicting distally located stenoses, SPECT was significantly superior to planar imaging for the left circumflex artery (p = 0.025). Concordance analysis of perfusion status showed agreement in 308 of 390 (79%) of coronary flow regions both with respect to the presence or absence of perfusion and to the reversibility or irreversibility of defects (kappa = 0.60, SE 0.04). Stress-induced perfusion defects were significantly more detected by SPECT than by planar imaging (p0.001). Based on SPECT findings 31 pts were proposed for revascularization compared to 30 pts based on planar imaging (NS). Overall there was agreement in 65 (83%) pts regarding treatment strategy. We conclude that in a head-to-head comparison SPECT provided improved diagnostic value compared with planar imaging. However, with respect to patient treatment, the superiority of SPECT was not always translated into improved patient management.

Aim of the study was to evaluate [99mTc]hexamethyl-propylamine-oxime (HMPAO) leukocyte scintigraphy for the assessment of disease activity and extent in inflammatory bowel disease patients. Results and scores of scintigraphy using [99mTc]HMPAO-labeled leukocytes were retrospectively compared with the activity index of van Hees, laboratory parameters, and gastroenterologists' assessment of disease using endoscopy, radiology, and histology plus clinical parameters in 136 patients with Crohn's disease (115) and ulcerative colitis (21) and in 29 controls. There were 114 positive and 22 negative [99mTc]HMPAO leukocyte scintigrams. Sensitivities for active disease at 1 and 3 hr were 98% and 98% and specificities were 100% and 83%, respectively. [99mTC]HMPAO leukocyte scintigraphy is superior to the activity index and the gastroenterologists' clinical assessment of active inflammation in IBD patients. Scintigraphy allows assessment of the existence, extent, and intensity of active inflammation in IBD patients in one examination with high accuracy.

Reinjection of thallium-201 (201Tl) improves the detection of myocardial ischaemia in approximately 50% of irreversible defects present on 3 h redistribution images. Additional reinjection studies, however, may limit the capacity of the nuclear laboratory and they are not patient-friendly Previous studies have suggested that only severe persistent defects with less than 50% of maximal 201Tl uptake are irreversibly damaged, with little chance of recovery following coronary artery bypass grafting (CABG). We examined the ability of a modified stress-reinjection protocol without redistribution imaging to predict subsequent improvement in myocardial perfusion post-CABG. Thirty-seven patients underwent quantitative planar stress/3 h reinjection 201Tl scintigraphy before and after uncomplicated CABG. After stress, segments were classified as normal (or = 75% maximum 201Tl uptake), moderate defect (50-75%) or severe defect (50%). After reinjection, they were classified as completely normalizing (or = 75%), partially improving moderate defect (increaseor = 10% but75%), partially improving severe defect (increaseor = 10% but50%), persistent moderate defect (10% increase) or persistent severe defect (50% initial uptake with10% increase). Scintigraphic classification was compared with left ventricular wall motion and post-operative classification. Of 336 initial stress defects, 264 (79%) were moderate defects and 72 (21%) were severe defects. After reinjection, 146 (55%) moderate defects normalized, 25 (9%) improved partially and 93 (35%) persisted. Nineteen (26%) severe defects normalized, 33 (46%) improved to become moderate defects, 7 (10%) improved only slightly and 13 (18%) persisted. Post-CABG, 201T1 uptake was normal in 123 of 146 (84%) completely normalizing moderate defects, 15 of 25 (60%) partially improving moderate defects, 53 of 93 (57%) persistent moderate defects, 11 of 19 (58%) completely normalizing severe defects and 13 of 33 (39%) partially improving moderate defects. None of the partially improving severe defects or persistent severe defects normalized. The sensitivity and specificity of detection of viability with pre-CABG stress-injection scintigraphy were 66% and 72% respectively, with pre-CABG wall motion 80% and 40% respectively, whereas in combination they resulted in a sensitivity and specificity of 94% and 70% respectively. We conclude that stress/3 h reinjection without redistribution imaging is a clinically feasible method for predicting myocardial 201T1 uptake post-CABG. The severity of defects and the pattern of change of uptake after stress-injection are related to the likelihood of normal 201T1 uptake post-CABG. Severe defects after reinjection are very unlikely to recover.

Interleukin-8 (IL-8) is a chemoattractant cytokine involved in chemotaxis and activation of neutrophils. Because in vivo administration of IL-8 induces mobilization of hematopoietic stem cells in mice, we assessed the mobilizing properties of IL-8 in rhesus monkeys. Recombinant human IL-8 was administered as a single intravenous injection at doses of 10, 30, and 100 micrograms/kg to rhesus monkeys (age, 2 to 3 years; weight, 2.5 to 4.5 kg). Venous blood samples were obtained at time intervals ranging from 1 to 480 minutes after IL-8 administration. Cell counts, colony-forming unit-Mix assays, and fluorescence-activated cell sorter analysis were performed. Plasma was harvested to assess IL-8 levels. A time-controlled bolus intravenous injection of 100 micrograms IL-8 per kilogram of body weight resulted in peak IL-8 plasma levels up to 5 micrograms/mL. The calculated half-time life of free IL-8 was 9.9 +/- 2.2 minutes. IL-8 injection resulted in instant neutropenia that was due to pulmonary sequestration, as shown using 99mTc-labeled leukocytes. Within 30 minutes after IL-8 injection, neutrophilia developed with counts up to 10-fold greater than baseline levels. The numbers of hematopoietic progenitor cells (HPCs) increased from 45 +/- 48/mL to 1,382 +/- 599/mL of blood at 30 minutes after injection of 100 micrograms IL-8 per kilogram of bodyweight (mean +/- SD, n = 8). Individual animals showed 10- to 100-fold increase in numbers of circulating HPCs that returned to almost pretreatment values (92 +/- 52 CFU/mL) at 240 minutes after the injection of IL-8. Immunophenotyping showed no significant changes in lymphocyte (sub)populations. A second bolus injection of IL-8 with an interval of 72 hours resulted in similar numbers of mobilized stem cells as observed after the first injection, showing that no tachyphylaxis had occurred. We conclude that IL-8 induces mobilization of HPCs from the bone marrow of rhesus monkeys in a rapid and reproducible fashion. Therefore, IL-8 may be a potentially useful cytokine in the setting of blood stem cell transplantation.

In small-cell lung cancer (SCLC), CT scan remains the most accurate imaging modality for evaluating local extension and specific sites of metastatic disease. The role of nuclear medicine in the work-up of SCLC is still limited to the detection of bone metastases. Recently, a new potential diagnostic tool has been introduced based on the presence of somatostatin receptors in SCLC. With the use of radiolabelled somatostatin analogues it is hoped that an equally effective but simpler staging system has been found that gives a better separation of prognostic subgroups. This article reviews the role of nuclear medicine in general and somatostatin receptor scintigraphy in particular in the imaging and staging of SCLC. Clinical value in terms of sensitivity and specificity is discussed in relation with other imaging and staging modalities.

To determine effectiveness of technetium-99m labelled polyclonal human immunoglobulin G (99mTc-IgG) scintigraphy to monitor variation in arthritis activity in patients with rheumatoid arthritis (RA).The results of semiquantitative 99mTc-IgG scintigraphy were compared with those of examination before and 26 weeks after initiation of parenteral gold treatment in 19 patients with RA.Clinical and laboratory variables of arthritis activity as well as the scores of 99mTc-IgG scintigraphy were significantly lower after gold treatment compared to the scores before treatment. However, the difference between the mean scores of 99mTc-IgG scintigraphy before and after treatment was statistically significant for more joints than such difference in scores for joint pain and joint swelling.99mTc-IgG scintigraphy is able to reflect variations in arthritis activity in patients with RA.

Prednisone is frequently used in the treatment of elderly-onset rheumatoid arthritis (RA), but the balance between efficacy and toxicity, including the effect on bone mass, has not been investigated in long-term studies. This prospective, randomized study was undertaken to compare disease activity and bone mass during long-term treatment with prednisone versus chloroquine in this patient population.Patients with active RA diagnosed at ageor = 60 were randomized to receive prednisone (15 mg/day for 1 month, with the dosage tapered as low as possible thereafter) (n = 28) or chloroquine (n = 28). Patients who did not show a response received other second-line drugs as an adjunct to prednisone or as a replacement for chloroquine. Bone mass was measured by dual-energy x-ray absorptiometry. The study duration was 2 years.During the 2 years, treatment with other second-line drugs was needed for 12 patients in the prednisone group (43%) and 8 in the chloroquine group (29%). Functional capacity and disease activity improved significantly in both groups and did not differ significantly between the groups, except for a greater improvement in the prednisone group at 1 month. Radiographic scores for joint destruction progressed similarly in both groups. There was a nonsignificant excess bone loss of 1.8% in the spine and 1.5% in the hip in the prednisone group, compared with the chloroquine group.Neither treatment was entirely satisfactory since a significant number of patients needed an additional second-line drug over the 2-year period.

This study addressed the following questions: How does 99mTc-IgG scintigraphy compare to physical examination in the detection of synovitis as determined histologically, and is 99mTc-IgG scintigraphy a sensitive detector of histologically documented synovitis activity in the absence of clinically detectable knee joint swelling?The results of measuring synovitis activity by physical examination and by scintigraphy with technetium-99m labelled polyclonal human immunoglobulin G (99mTc-IgG) were compared with the results of histological examination of synovial biopsies taken from the knee joints of patients with rheumatoid arthritis (n = 21), osteoarthritis (n = 9) and various other rheumatic diseases (n = 10).The sensitivity of 99mTc-IgG scintigraphy in detecting synovitis activity, as determined histologically (85%), was higher than the sensitivity of joint swelling (65%). In the absence of clinically detectable knee joint swelling the sensitivity of 99mTc-IgG scintigraphy was 83%.This study shows that 99mTc-IgG scintigraphy is a more sensitive method than physical examination in detecting histologically documented synovitis activity.

In this article clinical examples of extraskeletal localization of technetium-99m (99mTc)-labeled diphosphonate are described. In several of these cases this finding was relevant for clinical decision-making. 99mTc-labeled diphosphonates have been used for skeletal imaging since 1971, and from 1973 on many reports of extraskeletal localizations of these agents have been published. This visualization can be due to (1) an abnormality of the excretory route of 99mTc-labeled diphosphonate or (2) increased uptake in pathologically altered tissues and organs. The latter has been recorded in a multitude of disease processes, such as ischaemic injury, inflammatory processes, benign or malignant neoplasms, non-skeletal metastases, malignant pleuritis, scars, radiation injury and amyloidosis. Although the precise mechanism of extraskeletal uptake of 99mTc-labeled diphosphonate remains uncertain, binding of this radiopharmaceutical to calcium-containing compounds is thought to play a critical role.

Application of the Thallium-201 quantitative analysis method to Tc-99m Sestamibi planar myocardial perfusion images results in oversubtraction of tissue crosstalk, defined as 'activity within the myocardial image, which originated outside the heart'. A modified algorithm, specific for Tc-99m Sestamibi, was applied in 60 patients and the results of quantitative analysis to estimate the risk of coronary artery disease were compared with coronary angiographic findings and with visual analysis. New crosstalk planes were generated based on the results in 20 male healthy volunteers. The results in our study group indicate a higher diagnostic accuracy when circumferential profiles are generated on the basis of maximal counts compared to mean counts. Quantitative analysis was able to predict the presence or absence of CAD as accurately as visual analysis. Odds ratios were 1.07 and 1.32 respectively (P0.001) for both quantitative maximal uptake and visual uptake analysis. Sensitivity of visual analysis alone was 89%, increasing to 96% with combined visual/quantitative analysis. Specificity of visual analysis decreased from 79% to 64% with combined analysis. Although only minor differences are seen, the maximal count uptake profiles were found to have additional diagnostic value compared to visual analysis alone.

A gamma camera was equipped with a special collimator and arm assembly for bone mineral measurements with dual photon absorptiometry (DPA). The system was evaluated in vitro and in vivo and compared both with a rectilinear DPA and a dual energy X-ray (DEXA) system. All 3 systems showed a linear response in measurements of 4 vials, containing different amounts of hydroxyapatite. Phantom measurements with the gamma camera system showed a precision of 1.6% to 2.8%. Results obtained in 8 healthy volunteers with rectilinear and gamma camera systems were well correlated (R2 = 0.78). With the photon beam directed from posterior to anterior, the separation of vertebrae was easy with the gamma camera system. We conclude that bone mineral measurements can be made with a gamma camera for assessment of fracture risk and in the decision process whether a patient needs treatment or not. For follow-up, the precision of DPA with a gamma camera is inadequate.

Bone mass measurements were performed in a group of 30 ambulant, non-steroid treated female patients with rheumatoid arthritis (RA) of relatively short duration (mean 4.9 years). The bone mineral density (BMD) of the lumbar spine and femoral neck was assessed by dual-energy x-ray absorptiometry (DEXA), and related to parameters of disease activity and severity. Lumbar BMD was within the range of normal while femoral BMD was decreased compared to age-matched controls. BMD values, expressed as the percentage of age-matched healthy controls (BMD%), were positively related to the body mass index and negatively related to the number of swollen joints, the erythrocyte sedimentation rate and the platelet count. No relation was found between the lumbar and femoral bone mass on the one hand and disease duration, number of disease modifying anti-rheumatic drugs ever used, Ritchie articular index, C-reactive protein, functional ability or radiological scores on the other. It is concluded that in ambulant non-steroid treated female RA patients lumbar bone mass as measured with DEXA is within the range of normal, while femoral bone mass is slightly reduced. Both lumbar and femoral bone mass are related to the body mass index and parameters of disease activity.

In a prospective comparative study of 14 patients with inflammatory bowel disease (IBD), the abilities of 99mTc-HMPAO labeled white blood cells (WBCs) and 111In-granulocytes to assess the presence and location of active disease were compared. The two examinations were carried out within 2 wk of each other. Scintigraphically concordant positive or discordant segments were evaluated by radiologic or endoscopic examination performed within 14 days. When bowel segments were compared, concordance was found for 102/111 (91.8%) segments between 99mTc-WBC images obtained at 1 hr after injection and 3-hr 111In-granulocyte images. For five of five 99mTc-WBCs positive/111In-granulocyte negative segments, it could be proven that the 99mTc-WBC result was caused by active disease. For patients, 99mTc-WBC scintigraphy detected four more patients with active disease than 111In-granulocytes (11 and 7 patients, respectively). Technetium-WBCs was superior in the assessment of active disease, especially for small bowel segments. We conclude that early imaging 1 hr after the injection of 99mTc-WBCs can reliably replace 111In-granulocyte scintigraphy in IBD patients because the radiopharmaceutical is available on a daily basis. Thus, there is less radiation burden to the patient and cell separation is simpler and less time-consuming.

Thallium-201 reinjection following 3-4-hr redistribution imaging improves the detection of viable myocardium but considerably prolongs the total investigation time. We compared the results of immediate 201Tl reinjection with 3-hr redistribution imaging in 120 consecutive patients who were evaluated for myocardial ischemia. Thallium-201 was reinjected immediately following the postexercise study. The images were acquired 1 hr later and reacquired at 3 hr redistribution. A total of 960 segments per imaging series were evaluated, of which 320 (33%) segments showed perfusion defects on the post-exercise images. On the 1-hr images, 220 (69%) segments demonstrated enhanced thallium uptake, 97 (30%) segments did not change and 3 (1%) segments showed reverse redistribution. Of the 100 (97 + 3) persistent defects, only 12 (4%) segments showed fill-in of 201Tl on 3 hr redistribution images. A total of 49 (15%) segments showed reverse redistribution. Defects on postexercise images were seen in 95 patients (79%) of whom 9 (10%) showed no change on immediate reinjection images. In only 1 (1%) patient was the diagnosis changed from myocardial necrosis to myocardial ischemia after analysis of the 3-hr redistribution images. These data indicate that immediate postexercise reinjection of 201Tl followed by 1-hr image acquisition may be superior to 3-hr redistribution imaging in identifying viable myocardium in patients evaluated for myocardial ischemia. This protocol eliminates the need for an additional series of 3-4-hr redistribution images and offers the advantages of reduced total imaging time, improved convenience for the patient and increased patient throughput.

The additional diagnostic yield of exercise 201Tl scintigraphy using both visual and quantitative analysis was determined in 221 patients with known or suspected coronary artery disease (CAD). The coronary arteriogram was adopted as the gold standard. After pretest clinical and exercise electrocardiographic data were taken into consideration, scintigraphy added diagnostic accuracy both in the diagnosis of CAD and of multivessel disease. The diagnostic yield of the scintigraphy in terms of sensitivity and specificity was, however, not significant. In 79% (121/153) of the patients, the diagnosis of the presence, or exclusion, of CAD was highly probable (P0.80 or P0.20) when considering clinical and exercise data. The diagnosis was, however, not significantly improved by the scintigraphic result. Twenty-seven per cent (20/73) returned a negative scintigraphic results with a high (P0.80) prescintigraphic probability for CAD and a positive arteriogram. It was concluded that 201Tl scintigraphy has additional diagnostic value after clinical and exercise parameters were taken into consideration in the diagnosis of coronary artery and multiple vessel disease. It is not recommended to refer patients with either a low or high probability of CAD for screening and diagnosis as in a high proportion of patients the diagnosis of CAD could have been made using clinical or exercise data alone.

Bicycle exercise and treadmill exercise are the commonest devices used in the evaluation of coronary artery disease. However, not all patients are capable of performing a maximal exercise test due to orthopaedic, vascular or pulmonary disease, poor physical condition and motivation. Alternative tests as a reliable substitute for the more conventional methods have been proposed, such as right atrial pacing, arm ergometry, handgrip test, cold pressure test, and inotropic stimulation. In particular, pharmacological stress testing with dipyridamole (and recently with adenosine and dobutamine) in combination with radionuclide techniques has gained much interest. This review will consider the usefulness and role of alternative stress testing to provoke myocardial ischaemia, with emphasis on pharmacological stress testing in conjunction with thallium-201 myocardial perfusion scintigraphy.

The incremental diagnostic yield of exercise 201Tl scintigraphy with visual and quantitative analysis was determined in 191 patients with known or suspected coronary artery disease (CAD). The coronary arteriogram was used as the gold standard. After pre-test clinical and exercise electrocardiographic data were taken into consideration, scintigraphy was found to have additional diagnostic value both in the diagnosis of CAD and of multivessel disease, with quantitative analysis being superior to visual analysis. The impact of 201Tl scintigraphy on the patient's treatment--conservative treatment versus revascularization--was also evaluated. The impact was relatively low, as the decision for revascularization was based primarily on the angiographic result and the severity of the anginal pain. This result reflects only the decision making process used in our clinic and permits no conclusion to be made concerning the possible value of 201Tl scintigraphy in this type of medical decision making process.

The ability of 99mtechnetium labelled nonspecific, polyclonal human immunoglobulin G (99mTc-IgG) scintigraphy to depict and quantify synovial inflammation was studied in 30 patients with rheumatoid arthritis (RA). All patients were injected with 350 MBq 99mTc-IgG and imaging was performed 4 h later. This resulted in excellent images of inflamed synovium. Scores for 99mTc-IgG joint scintigraphy correlated highly with scores for joint swelling and C-reactive protein levels, weakly with pain scores and not with radiographic scores of joint destruction. These results suggest that 99mTc-IgG joint scintigraphy may provide an objective test to detect synovitis and measure the activity of the disease.

In bone densitometry, the precision of the instrument, the number of measurements and the time-points of the measurements are important criteria for monitoring bone mass changes. The most appropriate follow-up procedure can be determined by numerical comparison of various combinations of these three criteria. This can be done by computing the confidence interval of changes in bone mass. We developed a model to estimate the length of a confidence interval for the observed changes in individual patients. With specific instrument precision, a specified number of measurements and, assuming a linear rate of bone mass changes, the best estimate of the actual changes in bone mass is obtained by measurements at the end of an observation period. With the current precision of bone densitometers, follow-up of patients with yearly duplicate measurements is recommended. A shorter scan time interval offers no additional information unless very rapid bone loss is expected.

There is a need for an easily prepared radiopharmaceutical agent for the detection of inflammation and infection. In a group of 14 patients with inflammatory bowel disease (IBD), the detection of actively involved intestinal segments by nonspecific human polyclonal immunoglobulin (IgG) labeled with 99mTc was compared with that of 111In granulocytes. To determine the specificity of 99mTc-IgG scintigraphy, 8 control patients without clinical indications of intestinal inflammation were examined. 99mTc-IgG was found in the left colon in 8 and in the right colon in 7 of the 8 controls 4 hours after the injection. At that time of scintigraphy only 4 IBD patients exhibited a more intense accumulation at the site of the intestinal segments with active disease. In contrast, in a randomized comparison with 111In granulocytes scintigraphy was positive in 11 patients with the latter technique. Moreover, fewer diseased segments were seen in the 4 patients with positive 99mTc-IgG scintigraphy (6 versus 12 with 111In granulocytes). In view of the low sensitivity and specificity, it is concluded that 99mTc-IgG is not suitable for the scintigraphic staging of IBD patients.

We studied the cases of eleven patients in whom a rotationplasty had been done after wide resection of the distal part of the femur. All patients had had a malignant tumor of bone, but none had the complication of edema or leakage of lymph after the rotationplasty. We made lymphoscintiscans soon after the operation in four patients and weeks or months later in all eleven patients. There was a delay in the flow of lymph in three of the four patients who were examined lymphoscintigraphically soon after the operation and there was obstruction of flow in the fourth patient, but there was evidence of a decreased rate of flow in only two of the eleven patients at the time of the later examination.

Computed tomography, ultrasound, nuclear scintigraphy, and laboratory tests (lactic dehydrogenase, alkaline phosphatase, and 5-nucleotidase) were compared in 135 patients with gastro-intestinal carcinoma to define the most useful test to detect hepatic metastases. Thirty-six patients (26.7 per cent) had hepatic metastases at laparotomy. Sensitivities were low: 46.2 per cent for nuclear scintigraphy, 57.6 per cent for ultrasound, 67.7 per cent for computed tomography and 62.9 per cent for lactic dehydrogenase. Accuracies ranged from 62.9 (lactic dehydrogenase) to 77.6 per cent (nuclear scintigraphy). No significant differences were found. Accurate and efficient detection of hepatic metastases is hampered by relatively low sensitivity, specificity and accuracy of the conventional imaging tests and laboratory tests.

The conventional methods of CT scan (CT), ultrasound (US), scintigraphy (SC), and laboratory tests (LDH, AP, 5-Nt) were prospectively compared in 135 patients with gastrointestinal carcinoma to define the most useful test to detect hepatic metastases. Thirty-six patients (26.7%) had hepatic metastases at laparotomy. Sensitivities were low: 46% for SC, 58% for US, 68% for CT and 63% for LDH. Accuracies ranged from 62% (LDH) to 78% (SC). No significant differences were found. Accurate and efficient detection of hepatic metastases is hampered by the relatively low sensitivity, specificity and accuracy of conventional imaging and laboratory tests.

The diagnostic value of immediate post-exercise left ventricular ejection fraction (LVEF) was assessed in 161 patients at rest, during maximal exercise, and immediately post-exercise by radionuclide angiography. Fifteen patients had a second examination, giving a total of 176 radionuclide examinations. Additionally, the correlation between post-exercise LVEF and physical validity was investigated. Sixty-one patients (35%) with a recent myocardial infarction (less than 4 weeks), 66 patients (37%) with an old myocardial infarction (greater than 4 weeks), and 21 patients (12%) with valvular lesions were studied. Twenty-eight patients (16%) with an abdominal aneurysm were considered as controls based on history and a normal resting and exercise electrocardiogram (ECG). LVEF and a cumulative regional wall motion (RWM) score for three regions were obtained. LVEF post-exercise was significantly increased compared to LVEF at maximal exercise in all four diagnostic groups. Absolute LVEF values were significantly dependent on the level of exercise. We conclude that immediate post-exercise LVEF should not be used for separating patients with and without coronary artery disease.

Mutant frequencies were measured in T-lymphocytes of patients undergoing radionuclide angiography with erythrocytes labeled in vivo with technetium-99m. Blood from 13 patients was sampled before and after (8-120 days) an injection with 750 MBq technetium-99m. Frequencies of HPRT- mutants were measured with the T-cell cloning method. Results indicated that the mean frequency of mutants after treatment was significantly below that measured before exposure. Thus, in contrast to published data, our results do not support the conclusion that radionuclide angiography with technetium-99m induces HPRT- mutations. Further analysis of our data indicated that the decrease in mutant frequency after exposure can be accounted for by an effect of cloning efficiency.

Serum concentrations of IgG may influence Fc receptor-mediated clearance of immune complexes. For instance, when 123I-labeled aggregates of human IgG (123I-AIgG), used as a model for soluble immune complexes, are administered to patients with systemic lupus erythematosus (SLE), there is an inverse correlation between the serum concentrations of IgG and the clearance and volume of distribution in steady state (Vss) of 123I-AIgG. To answer the question whether IgG has a direct effect on the clearance of immune complexes, we measured the elimination of 123I-AIgG in eight patients with hypogammaglobulinemia, before and after substitution with intravenous gammaglobulin (IVIG). As expected, raising IgG concentrations in these patients (by 6 g/l) caused a significant decrease of the Vss of 123I-AIgG. However, clearance of 123I-AIgG remained unchanged by IVIG. Thus, the results of this study offer no experimental evidence that raising concentrations of IgG influences the clearance of soluble immune complexes.

The purpose of this study was to investigate both the ability of 99mTc-labeled polyclonal human immunoglobulin (HIG) to localize an infection and the modes of action involved in this process. Mice, infected with Staphylococcus aureus ATCC 25923 in a thigh muscle, received HIG intravenously. Scintigrams were made 1, 4, and 24 hr later; subsequently the mice were killed and the activity in several organs and thighs was determined. The radiopharmaceutical demonstrated a time-dependent accumulation at the site of infection. It was found that vascular permeability or Fc binding alone could not account for the mode of action of HIG. Neither the origin of Ig (human versus murine) nor the total amount of protein (0.01-1.0 mg Ig per mouse) affected the target-to-background (T/B) ratios. Ratios were not different for leukocytopenic animals. A correlation (p less than 0.001) was demonstrated between the number of bacteria at the site of infection and the T/B ratio. This was also found after antibiotic treatment (p less than 0.02).

In a group of 72 patients with acute myocardial infarction who underwent a maximal symptom-limited predischarge exercise test in conjunction with radionuclide angiography, 25 (35%) showed greater than 1 mm asymptomatic ST-T-segment depression during exercise. All 25 patients underwent repeated exercise radionuclide angiography 2 days later, 2 h after oral intake of 120 mg diltiazem. Double product was not significantly different before and after diltiazem both at rest and during exercise. Maximal ST-T-segment depression after diltiazem was reduced from 2.4 +/- 0.9 mm to 0.8 +/- 0.6 mm (p less than 0.01). Left ventricular ejection fraction (LVEF) at rest was (before diltiazem) 52.1 +/- 8.9% and (after diltiazem) 55.1 +/- 12.3% (NS). During exercise, LVEF improved after diltiazem from 42.8 +/- 12.1% to 49.1 +/- 10.8% (p less than 0.05). Regional wall motion score (1 = normal, 2 = hypokinetic, 3 = akinetic, 4 = dyskinetic) at rest before diltiazem was 9.9 +/- 2.3 and, after diltiazem, was 9.0 +/- 1.9 (NS). During exercise, regional wall motion score improved after diltiazem from 5.9 +/- 1.3 to 4.2 +/- 1.2 (p less than 0.02). We conclude that diltiazem has acute beneficial effects on asymptomatic ST-T-segment depression and on global and regional left ventricular function in post-infarction patients with silent ischemia.

Four 99mTc and three 123I labeling methods were evaluated for their suitability to label low density lipoproteins (LDL) for the purpose of scintigraphic biodistribution studies. For 99mTc these methods were: direct incorporation in LDL of 99mTcO4- using sodium dithionite (dithionite method); a method using first N,N-dimethylformamide to prepare a 99mTc-complex reacting with LDL in a subsequent step (DMF method); a technique in which 99mTcO4- is first coupled to a diamide dithiolate derivative of pentanoic acid by reduction with dithionite, followed by coupling of this ligand to LDL (N2S2 method); and a method using sodium borohydride and stannous chloride as reducing agents (borohydride method). The iodination techniques were based on oxidation of I(-)----I+, using iodine monochloride (ICl method), 1,3,4,6-tetrachloro-3,6-diphenylglycoluril (Iodogen method), and N-bromosuccinimide (NBS method) as oxidants. We studied labeling yields, modification of LDL caused by the labeling procedures using agarose-gel electrophoresis, and radiochemical stability of the labeled LDL complex upon incubation in plasma at 37 degrees C for 15 h. We used Sepharose CL6B chromatography to separate LDL from other plasma proteins. We also examined whether LDL isolated from frozen plasma (Pool-LDL) gave results similar to LDL obtained from freshly prepared plasma (Fresh-LDL). Pool-LDL radiolabeled by the dithionite, DMF, NBS, and Iodogen methods lost its label upon incubation with plasma. This also happened with Fresh-LDL when the DMF, NBS and Iodogen methods were used. Upon agarose-gel electrophoresis, no modification of LDL was observed with all methods when the radionuclide/LDL ratio was kept low.(ABSTRACT TRUNCATED AT 250 WORDS)

Visual assessment and quantitative analysis of exercise thallium-201 myocardial perfusion scintigraphy was performed in 203 consecutive patients who underwent coronary arteriographic studies to identify the factors associated with false negative and false positive studies. Also the discordance between visual and quantitative analysis was evaluated. One hundred sixty-two (80%) of these 203 patients had significant coronary artery disease (CAD), i.e. a luminal stenosis greater than or equal to 50%. Fifty-two (32%) of these 162 patients with documented CAD showed negative thallium results either by visual or quantitative analysis. When interpreted visually 36/162 (22%) of patients were judged as negative, and when analyzed quantitatively 41/162 (25%) of patients were judged as negative (ns). Of the total group of 52 patients with false negative visual and/or quantitative analysis test results, 27 (17%) showed discordance between these two methods. Of the 41 patients without significant CAD, 12 (29%) showed positive thallium findings. Visual interpretation was positive in 9/41 (22%) of patients without significant CAD, and quantitative analysis in 5/41 (12%) (ns). Of the total group of 12 patients with positive visual and/or quantitative analysis test results, 10 (24%) showed discordance between these two methods. Therefore, in the total group, 37 patients (18%) showed discordance between visual and quantitative analysis. It is concluded that 1) the sensitivity and the specificity of visual interpretation and quantitative analysis of thallium-201 exercise scintigraphy for detecting CAD is similar, and 2) that there is frequent discordance of visual interpretation and quantitative analysis in thallium-201 exercise scintigraphy.

A summary is given of data on the clinical experience with the anti-melanoma antibody 225.28S in ophthalmology and the tissue expression of the high molecular weight-melanoma associated antigen in choroidal melanoma. Results are discussed in relation to other detection methods for ocular melanoma currently employed by the ophthalmologist.

The estimation error due to variations in soft-tissue baseline in lumbar bone mineral content (BMC) measured by dual-photon absorptiometry (DPA) was calculated with a new method of automatic baseline subtraction. In water phantom measurements, the s.d. of the soft-tissue (ST) baseline matched closely (r = 0.98) to the random error, calculated using 44 keV and 100 keV count rates and the directly determined baseline variations. In 21 volunteers and in 70 patients with osteoporosis, the ST variations were larger than the expected random error, revealing a source of error related to the inhomogeneity of soft tissue. The estimation error in BMC caused by ST variations was 0.7% in healthy subjects (mean BMC 40.5 gHA) and 1.5% in patients (mean BMC = 26.4 gHA). These results indicate that ST-related errors are an important limit to the precision of lumbar DPA measurements.

While studying the uptake of iodine-123-metaiodobenzylguanidine ([123I]MIBG) in chemodectomas, we coincidentally detected catecholamine secreting tumors in 5 out of 14 patients. In three of these cases, a norepinephrine secreting abdominal paraganglioma was subsequently removed. One patient had a norepinephrine secreting chemodectoma and one had a dopamine secreting chemodectoma. Prior to [123I]MIBG imaging and urinary catecholamine measurements, endocrine activity was suspected in only one of these five patients. Apart from these five cases, two other patients showed elevated catecholamine secretion and abnormal abdominal [123I]MIBG concentrations. However, these two patients were not surgically explored, because of normal computed tomography (CT) and magnetic resonance (MRI) studies. We suspect that catecholamine-secreting tumors are more common in patients with chemodectomas than is assumed in the literature, and we therefore recommend urinary catecholamine screening for all patients with chemodectomas. In case of elevated catecholamine secretion, MIBG scintigraphy is indicated.