18F-FDG labelling of human leukocytes.

Radiolabelled leukocytes are useful for the imaging of inflammation and infection, and 18F-fluorodeoxyglucose (18F-FDG) is known to concentrate in metabolically active cells. We evaluated the feasibility of leukocyte labelling with 18F-FDG using ACD and heparin anticoagulants at 20 degrees C and 37 degrees C, with and without gentle mixing during incubation. With leukocytes (WBC) harvested from 20 ml blood, studies were performed using 18F-FDG in concentrations of 3.7-74 MBq (0.1-2.0 mCi). 18F-FDG WBC stability in platelet-poor plasma was assessed at 1-4 h. Satisfactory labelling efficiency was achieved with incubation in heparin-saline at 37 degrees C for 30 min (62.7+/-1.6%), and was further enhanced by mixing during incubation (78.1+/-3.9%). Cell labelling was predominantly of granulocytes (78.5+/-1.4%). 18F-FDG WBC was relatively stable in platelet-poor plasma for up to 4 h, and no cell staining was observed in viability studies using trypan blue. These results indicate the feasibility of leukocyte labelling with 18F-FDG, providing an approach that may be useful in PET imaging of inflammation and infection.

Biodistribution and radiation dosimetry of stabilized 99mTc-exametazine-labeled leukocytes in normal subjects.

UNLABELLED: Labeling leukocytes with 99mTc-exametazime is a validated technique for imaging infection and inflammation. A new radiolabeling technique has recently been described that enables leukocyte labeling with a more stable form of 99mTc-exametazime. A normal value study of stabilized 99mTc-exametazime-labeled leukocytes has been performed, including biodistribution and dosimetry estimates in normal subjects. METHODS: Ten volunteers were injected with stabilized 99mTc-exametazime-labeled autologous leukocytes to study labeled leukocyte kinetics and dosimetry in normal subjects. Serial whole-body imaging and blood sampling were performed up to 24 h after injection. Cell-labeling efficiency and in vivo viability, organ dosimetry, and clearance calculations were obtained from the blood samples and imaging data as well as urine and stool collection up to 36 h after injection. RESULTS: Cell-labeling efficiency of 87.5% +/- 5.1% was achieved, which is similar to or better than that reported with the standard preparation of 99mTc-exametazime. In vivo stability of the radiolabeled leukocytes was also similar to in vitro results with stabilized 99mTc-exametazime and better than previously reported in vivo stability for nonstabilized 99mTc-exametazime-labeled leukocytes. Organ dosimetry and radiation absorbed doses were similar with a whole-body absorbed dose of 1.3 x 10(-3) mGy/ MBq. Urinary and fecal excretion of activity was minimal, and visual assessment of the images showed little renal parenchymal activity and no bowel activity up to 2 h after injection. CONCLUSION: Cell labeling and in vivo stability appear improved compared with the leukocytes labeled with the nonstabilized preparation of 99mTc-exametazime. There are advantages in more cost-effective preparation of the stabilized 99mTc-exametazime and an extended window for clinical usage, with good visualization of abdominal structures on early images. No significant increase in specific organ and whole-body dosimetry estimates was noted compared with previous estimates using nonstabilized 99mTc-exametazime-labeled leukocytes.

Clinical experience with radiolabelled monoclonal antibodies in the detection of colorectal and ovarian carcinoma recurrence and review of the literature.

A retrospective study was carried out to determine the diagnostic value of OncoScint CR/OV immunoscintigraphy in assessing patients with suspected recurrence of carcinoma of the colon and ovary. The scintigraphic results of 31 patients were compared with surgical and histopathological findings, conventional radiological examinations and clinical disease outcome over an average 3-year follow-up. Detected lesions were divided by location into hepatic or extrahepatic and the latter group was classified as local recurrence at the resection site, pelvic or abdominal regional lymph node involvement and distant metastatic disease. The combined sensitivity and accuracy of immunoscintigraphy in the detection of extra-hepatic disease was significantly higher than that of cross-sectional radiological imaging (87% and 83% vs 44% and 53% respectively) with equal specificity of 74%. Scintigraphy identified 14 (36%) of 39 extra-hepatic malignant lesions not diagnosed by conventional radiological techniques and influenced therapeutic planning in 8 (26%) of 31 patients studied. In the liver, conventional imaging had a significantly higher detection rate than immunoscintigraphy (sensitivity 93% vs 28%). In conclusion, these results show that OncoScint scintigraphy is a sensitive method for the detection of local recurrence and extra-hepatic metastases in colorectal and ovarian carcinoma and has an important role in the therapeutic decision-making process.

Suspected non-small cell lung cancer: incidence of occult brain and skeletal metastases and effectiveness of imaging for detection--pilot study.

PURPOSE: To estimate the incidence of occult metastases to the brain and skeleton in patients suspected of having non-small cell lung cancer (NSCLC) (stage higher than T1Nomo) with surgically resectable disease, to assess the accuracy of screening magnetic resonance (MR) imaging and radionuclide bone scanning for help in identifying occult metastases, and to determine the effectiveness of a high dose of MR contrast material. MATERIALS AND METHODS: Twenty-nine patients suspected of having NSCLC localized to the lung or to the lung and regional nodes underwent preoperative MR imaging with contrast material enhancement and radionuclide bone scanning for detection of brain or skeletal metastases. Patients were followed up for 12 months to determine the incidence of clinical metastatic disease. RESULTS: Eight (28%) patients had occult metastatic disease to the brain or skeleton. Brain metastases were identified on MR images in five of six patients. Bone metastases were identified on MR images in four of five patients and on bone scans in three of five patients. MR imaging was no more accurate than bone scanning for skeletal evaluation. A high dose of MR contrast material allowed detection of more metastases and of small lesions. CONCLUSION: Contrast-enhanced MR imaging of the brain is indicated for the exclusion of brain metastases in patients with clinically operable known or possible NSCLC and a large (> 3-cm) lung mass. Skeletal imaging may be indicated if an isolated brain metastasis is detected.

Medium-term effects of a new 5HT3 antagonist, alosetron, in patients with carcinoid diarrhoea.

BACKGROUND: Carcinoid diarrhoea is associated with rapid small bowel and proximal colonic transit. Intravenous administration of a serotonin type 3 receptor (5HT3) antagonist restores postprandial colonic tone towards normal in carcinoid patients. AIMS: To evaluate the medium-term effects of an oral 5HT3 antagonist, alosetron, on symptoms, stool fat, and transit in patients with carcinoid diarrhoea. METHODS: In 27 patients with carcinoid diarrhoea, symptoms were recorded daily and gastrointestinal transit was measured by scintigraphy in a three dose (0.1, 0.5, 2.0 mg, twice daily), randomised (1:1:1), parallel group, four week study. Placebo was given during the first week. Loperamide (2 mg capsules) was used as rescue medication. RESULTS: There were numerical improvements in median diarrhoea score, stool weight, loperamide use, and overall colonic transit at four hours, but no overall significant drug effect was shown. Alosetron reduced the proximal colon emptying rate (p < 0.05 in 20 evaluable comparisons), but did not significantly alter small bowel transit. CONCLUSIONS: Alosetron retardation of proximal colonic emptying in patients with carcinoid diarrhoea confirms the potential role of a 5HT3 mechanism in this disorder. Doses of alosetron higher than 2.0 mg twice daily will be required for symptomatic benefit in carcinoid diarrhoea.

Reproducibility and simplification of 13C-octanoic acid breath test for gastric emptying of solids.

OBJECTIVE: The accuracy of the 13C-octanoic acid breath test is enhanced by breath sampling over 6 h rather than 4 h, but this increases the cost of the test. Our aim was to validate a less costly but accurate sequence of breath sampling for measuring gastric emptying of solids. METHODS: We performed the 13C-octanoic acid breath test and tested its reproducibility relative to simultaneous scintigraphy in 30 healthy volunteers. RESULTS: There was a significant but weak correlation between t1/2 measured by the two tests (rs = 0.54, p < 0.005), but not between the duration of the lag phase. The differences in the t1/2 measurements between the tests were different between subjects but were highly reproducible within subjects. Within- and between-subject variations of measurements of gastric emptying with the 13C-octanoic acid breath test were not significantly different from the variations observed with scintigraphy. A subset of 11 breath samples collected over 6 h (24 samples) predicted (r2 > 0.95) the variables characterizing the cumulative appearance of 13CO2 in breath; these samples were at 35, 50, 95, 110, 140, 155, 215, 245, 260, 290, and 335 min. The accuracy of this subset of sampling times was confirmed in a separate set of breath test samples over 6 h from the same 30 subjects. CONCLUSIONS: The 13C-octanoic acid breath test for gastric emptying of solids is as reproducible as scintigraphy. A subset of 11 sampling times provides sufficient information to characterize the whole breath-test curve, but the sampling period should be extended to 6 h after dosing.

Colonic transit scintigraphy labeled activated charcoal compared with ion exchange pellets.

UNLABELLED: Scintigraphic measurement of colonic transit is currently performed by delivering 111In ion exchange resin pellets to the colon in a methacrylate-coated capsule. However, use of this method is constrained by the need for an investigational drug permit. We have demonstrated previously optimal adsorption in vitro of commonly used radioisotopes (e.g., 99mTc or 111In) to activated charcoal in milieus that mimicked gastric and small intestinal content. The aim of this study was to compare the transit profiles of radioactive activated charcoal and resin pellets delivered to the colon in the same methacrylate-coated capsule. METHODS: In 10 healthy volunteers, we compared the colonic transit profiles over 32 hr of simultaneously administered resin pellets labeled with 111In and activated charcoal mixed with 99mTc-diethylenetriaminepentaacetic acid. Transit was summarized as the geometric center (weighted average of counts) in the colon at each scanning period. RESULTS: Colonic transit profiles were virtually identical with the two markers, with less than 0.1 geometric center unit differences in the transit profiles over the 32-hr periods. CONCLUSION: Activated charcoal is a suitable alternative to resin pellets when delivered in a methacrylate-coated, delayed-release capsule to the colon for measurement of transit by scintigraphy.

The effects of anagrelide on human megakaryocytopoiesis.

Anagrelide, an inhibitor of platelet aggregation, decreases the number of platelets in normal subjects and in patients with myeloproliferative disorders. We describe studies aimed at discovering the general mechanism(s) by which anagrelide acts. We examined three hypotheses: (1) anagrelide shortens platelet survival, (2) anagrelide inhibits the proliferation of megakaryocytic-committed progenitor cells (CFU-M), and (3) anagrelide inhibits maturation of megakaryocytes. We observed that anagrelide did not shorten platelet survival. Proliferation of CFU-M in vivo was not affected by anagrelide, although high concentrations of anagrelide inhibited CFU-M in vitro. In-vivo and in-vitro anagrelide altered the maturation of megakaryocytes, causing a decrease in their size and changing other morphometric features. We conclude that anagrelide decreases the number of platelets primarily by interfering with the maturation of megakaryocytes.

[13C]octanoic acid breath test for gastric emptying of solids: accuracy, reproducibility, and comparison with scintigraphy.

BACKGROUND & AIMS: Previous work suggested that a breath test using 13C accurately measures gastric emptying of solids. Thus, breath test half emptying time (t1/2) minus 66 minutes was claimed to estimate accurately t1/2 by scintigraphy. The aim of this study was to evaluate the accuracy and reproducibility of this breath test in healthy subjects. METHODS: Fifteen volunteers (8 men and 7 women; mean age, 41 +/- 13 years) underwent simultaneous scintigraphy and [13C]octanoic acid breath test. Scans and breath samples were obtained every 15 minutes for 4 and 6 hours, respectively. The breath test was repeated three times within a 3-week period. RESULTS: Parameters from scintigraphy and breath test were not correlated significantly. Differences of lag phase and t1/2 between the two tests were highly variable (range for t1/2, -33.1 to 169.6; mean, 48.0 minutes). Increasing breath test "duration" (samples over 4, 5, or 6 hours) yielded decreasing estimates of the lag phase and t1/2. Although widely different values were observed in some subjects, repeated breath tests showed a high degree of reproducibility within individuals (mean coefficient of variation, 12%). CONCLUSIONS: [13C]Octanoic acid breath test for gastric emptying of solids requires further validation before it can substitute for scintigraphy as a diagnostic test, but it seems useful for intraindividual comparisons.

Technical pitfalls in image acquisition, processing, and display.

Optimal image quality is an ideal in nuclear medicine that is not always realized, being subject to a variety of conditions that can act, either singly or in combination, to undermine its accomplishment. These conditions include potential defects and limitations in both the hardware and software used for the acquisition and reconstruction of nuclear medicine images. Factors relating to individual patients can contribute to these obstacles, including limitations in mobility and compliance. Importantly, suboptimal or erroneous technique is a common source of poor imaging results, with loss of diagnostic efficacy. Appropriate test selection and careful attention to patient preparation and procedural details are essential elements in avoiding image flaws and artifacts in nuclear medicine.

Patient-related pitfalls and artifacts in nuclear medicine imaging.

Quality control in nuclear medicine is all important. This applies not only to preparation of the patient and acquisition of the image, but also to interpretation of the study. Although it may seem self-evident, it is important to remain aware of artifacts that are directly related to the patient and need special consideration. Furthermore, at times the distinction between normal variants and artifacts can be difficult. Commonly encountered patient-related artifacts include artifacts caused by attenuation, contamination artifacts, and artifacts caused by intravenous lines, tubes, and catheters. Less commonly, artifacts arise because of the use of multiple isotopes, the presence of fistulas or surgically altered anatomy, and pharmaceuticals and other substances interfering with expected radiopharmaceutical uptake and distribution. The diagnostic accuracy of nuclear medicine reporting can be improved by awareness of these patient-related artifacts. Both awareness and experience are also important when it comes to detecting and identifying normal (and abnormal) variants.

Bone scintigraphy evaluated in diagnosing and staging Langerhans' cell histiocytosis and related disorders.

UNLABELLED: An analysis of patients with proven Langerhans' cell histiocytosis (LCH) was undertaken with the aim of evaluating the role of bone scintigraphy in the diagnosis and staging of LCH. METHODS: Radiographic skeletal surveys and whole-body bone scintigraphy study results were reviewed for all patients treated at the Mayo Clinic in Rochester, Minnesota during 1965-1994 with histologic proven LCH. All available studies were then reported in a randomized and blinded fashion. RESULTS: Of the 73 patients with the histologic diagnosis, 56 (76%) had a definite lesion reported on radiographs and subsequent biopsy-proven bone involvement. For this population, the sensitivity and specificity of radiographic survey were 100% and 61%, respectively, compared to 91% and 55% for bone scintigraphy. Solitary bone lesions were reported on 21 radiographic surveys and 24 bone scintigrams. For solitary lesions, radiograph sensitivity and specificity were 95% and 73%, respectively, compared to 88% and 77% for bone scintigraphy. Bone scintigraphy receiver operating characteristic curves showed the region of greatest diagnostic accuracy to be skull, facial bones and mandible (88% sensitivity, 52% specificity). Radiation dosimetry to adult reproductive organs was less favorable for radiographic skeletal survey compared to bone scintigraphy. CONCLUSION: Our results support the use of radiographic skeletal survey in the initial diagnosis of LCH. Bone scintigraphy may have a role in monitoring a patient's progress in which the initial scintigram and radiographic survey show good correlation.

111In-CYT-103 scanning in recurrent colorectal cancer--does it affect standard management?

PURPOSE: In a blinded fashion, radiolabeled B72.3 was investigated in operative cases of recurrent colorectal cancer to determine if diagnostic accuracy would be improved to ultimately maximize curability and minimize interventional morbidities. METHODS: Study patients underwent conventional evaluation including history, physical examination, abdominal/pelvic computed tomographic scan (CT), colon examination, and carcinoembryonic antigen (CEA) determination, with select magnetic resonance imaging and ultrasonographic imaging as indicated. Murine monoclonal antibody B72.3 was labeled with indium-111 (111In-CYT-103 provided by Cytogen) and scans obtained at 48 hours and, selectively, at 72 and 96 hours. Unlike previous studies, the operating surgeon was blinded to 111In-CYT-103 abdominal scan results until surgical exploration was complete. RESULTS: Of 15 study patients (10 male; 5 female), average age was 57 years, and average CEA was 10 ng/ml (with eight elevated CEA levels). A single patient did not undergo surgery because of presence of pulmonary metastases identified on CT scan but not identified on a 111In-CYT-103 scan. Laparotomies included resection and intraoperative radiation (10), resection alone (1), and biopsy only (3). CT and 111In-CYT-103 scans were compared with operative findings. CT scans had an accuracy and positive predictive value of 47 and 100 percent, respectively, whereas those of 111In-CYT-103 scan were 60 and 82 percent, respectively. Contribution of the scan to diagnosis and management was graded by the surgeon as no effect (67 percent), beneficial effect (13 percent), or negative effect (20 percent). CONCLUSIONS: 111In-CYT-103 was more accurate compared with CT scan, but when value of the scan was examined with respect to its potential contribution to patient management, it was beneficial in only 13 percent of patients. Further refinements may enhance the value of antibody imaging techniques.

Granulocyte accumulation in the transplanted liver does not correlate with clinical and histologic evidence of dysfunction.

RATIONALE AND OBJECTIVES: To evaluate the role of granulocytes in reperfusion injury after liver transplantation. The authors injected radiolabeled granulocytes to determine if human liver graft outcome could be correlated with granulocyte accumulation. MATERIALS AND METHODS: Pure granulocyte suspension was prepared from eight patients 12 to 24 hours after orthotopic liver transplantation. The granulocytes were labeled with indium-111 (111In) oxine and reinjected. Total body radionuclide images were performed. Liver uptake of granulocytes was compared with biochemical and histologic evidence of liver injury. RESULTS: No correlation was found between liver uptake of granulocytes, as measured by geometric mean counts, and the biochemical or histologic measures of liver injury. Liver uptake of 111In was 9.6% for the patient who had liver dysfunction and 10.4% mean of the study group. This technique did not detect early signs of liver dysfunction. CONCLUSIONS: This investigation supports the premise that granulocytes do not play a major role in reperfusion injury of the newly transplanted liver graft.

Evaluation of 201Tl SPET myocardial perfusion imaging in the detection of coronary artery disease after orthotopic heart transplantation.

Accelerated coronary artery disease is a common complication following orthotopic cardiac transplantation. The relationship between acute rejection and accelerated coronary artery disease remains unclear. While thallium-201 (201Tl) imaging has been advocated in the diagnosis of post-transplant coronary arteriopathy, other investigators have found little role for this technique in the evaluation of such patients. We undertook a retrospective review of 13 stress/rest (10 exercise, 2 dobutamine, 1 dipyridamole) and 2 rest/rest 201Tl single photon emission tomographic (SPET) imaging studies performed in seven patients post-cardiac transplantation (mean duration post transplantation = 2.5 years). Four of these patients had serial studies with an average interval between studies of 8.3 months (range 3-14 months). Coronary angiography was performed within 12 months of each 201Tl study (mean = 4.2 months). Using the coronary angiographic diagnostic criterion of > or = 50% stenosis in one or more vessels, one or more fixed or reversible segmental defects were found on 201Tl imaging with a sensitivity of 78% and specificity of 33%. When the angiographic criterion of > 70% stenosis in one or more vessels was used the sensitivity increased to 100%, and where reversible segments were diagnostic the sensitivity was 67% and the specificity range from 42 to 58%. Although based on a small sample of patients, these results suggest that use of appropriate test methods and interpretive criteria may improve the utility of 201Tl SPET myocardial imaging in the diagnosis of coronary artery disease in cardiac transplant patients. Limited specificity may reflect associated pathological processes in these patients, including rejection, oedema and focal inflammation.

A pilot study of splenic and whole body retention of autologous radiolabeled leukocytes in the assessment of severity in inflammatory colitis.

OBJECTIVE: To assess the splenic and whole body retention of radiolabeled autologous leukocytes over 24 or 48 h as measures of the severity of colitis. METHODS: Eleven patients with colitis underwent standardized clinical, endoscopic, histological, and 111In-labeled leukocyte scintigraphy. A logistic discriminant analysis was used to estimate weighting factors for morphological indices, serum albumen, and stool excretion of 111In over 24 h that predicted the clinical assessment of severity. Subsequently, Spearman rank correlation analysis estimated associations among reductions in spleen and whole body radioactivity and the derived indices of inflammation. RESULTS: The reduction in spleen counts over 24 h correlates significantly with morphological indices (rs = 0.83, p < 0.005) and with serum albumen and stool 111In (functional index, rs = 0.77, p < 0.01). Similarly, the reduction in whole body 111In over 48 h correlates significantly with the combined index (rs = 0.8) and with the morphological and functional index separately (rs = 0.72 and 0.79, respectively). CONCLUSION: This pilot study identified weighting factors for morphological and functional indices in assessing severity of colitis; reduction in whole body and splenic retention of radioactivity was sufficient for evaluation of severity of colitis without the need for stool collections.

111In-oxine-labelled granulocyte dosimetry in normal subjects.

The aim of this study was to determine organ uptake and dosimetry in human subjects using 111In granulocytes obtained by ficoll-hypaque purification. Anterior-posterior whole-body imaging was performed at 1, 3, 5, 24 and 48 h after injection of approximately 18.5 MBq (0.5 mCi) 111In granulocytes in 10 normal volunteers. Utilizing relative geometric mean analysis, the fraction of injected activity (FIA) was determined at each imaging time for the kidney, liver, lungs, bone marrow, spleen and whole-body remainder. Residence time was determined by integration of the bi-exponential fit of the FIA data over time. Curve fitting was performed with SAAM software (University of Washington). Red marrow uptake was calculated from activity in the L3-L4 vertebrae and iliac crests. Total body marrow uptake was extrapolated from these data using ICRP 23. Dose was determined with MIRDOSE 2 for the various organs. The liver had the highest organ uptake (40.3% at 48 h). The spleen, liver, red marrow, kidney and lung doses were 4.1, 1.6, 0.8, 0.5 and 0.4 mGy MBq-1, respectively. Urinary and stool excretion was negligible and blood clearance half-time was 6.9 h. Using current methods providing improved quantification of organ uptake and dosimetry, our results confirm the liver, spleen, bone marrow,lungs and kidneys to be the principal target organs of 111In granulocytes.