Imaging infection with LeuTech.

LeuTech is a 99Tcm labelled, anti-CD15, IgM, murine monoclonal antibody shown to have high affinity (Kd = 10(-11) M) for CD15 receptors (5.1 x 10(5)/cell) expressed on human neutrophils. LeuTech was injected directly, intravenously, and its efficacy in imaging infection in 46 consecutive patients was determined. Human anti-mouse antibody (HAMA) response was examined in 30 normal volunteers using a standard LeuTech dose reconstituted with decayed 99Tcm solution. There were 38 true positive, six true negative, and two false negative scans. Of the 38 positive images, 33 (92%) were positive within 10 min after injection of LeuTech. LeuTech accuracy in this group of patients was 96%, sensitivity 95%, specificity 100%, positive predictive value (PPV) 100%, and negative predictive value (NPV) 75%. No elevation of the HAMA titre was observed in any of the 30 normal volunteers and no adverse reaction was noted in any patient. LeuTech is a highly promising agent for rapid imaging of infectious foci.

Scintigraphic determination of equivocal appendicitis.

We evaluated Tc-99m-labeled anti-CD15 immunoglobulin M monoclonal antibody (LeuTech) for scintigraphic detection of acute appendicitis in patients with an equivocal clinical presentation. LeuTech avidly binds to circulating and sequestered human polymorphonuclear neutrophils in vivo eliminating the need for in vitro cell labeling and the risks of blood handling. We studied 99 patients to evaluate the safety and efficacy of LeuTech imaging. Serial dynamic and static planar images were acquired for up to 3 hours after the intravenous administration of 10 to 20 mCi of Tc-99m LeuTech. Scans were read as positive or negative for acute appendicitis or other intra-abdominal infection. The institutional diagnosis was established by surgery and histopathology of the appendix, results of other diagnostic studies, or 2-week clinical follow-up. Scans were positive for appendicitis in 39 of 40 patients with appendicitis at surgery (sensitivity 98%) and negative for appendicitis in 49 of 58 patients without appendicitis (specificity 84%). One was lost to follow-up. Accuracy, positive predictive value, and negative predictive value were 90, 81, and 98 per cent respectively. In patients with appendicitis and positive scans more than 50 per cent of the images were positive at 4 minutes, and all were positive by 1 hour. Mean time of first positive image was 15 minutes. There were no serious adverse reactions. We conclude that LeuTech imaging is a highly sensitive test for detection of appendicitis in equivocal cases. There are advantages of this agent over the other currently used radiotracers in terms of convenience and time to diagnosis particularly the rapidity with which acute appendicitis will be seen on the images.

Neutrophil-specific 99mTc-labeled anti-CD15 monoclonal antibody imaging for diagnosis of equivocal appendicitis.

UNLABELLED: We evaluated 99mTc-labeled anti-CD15 immunoglobulin M monoclonal antibody (LeuTech) for diagnosing acute appendicitis in patients with an equivocal clinical presentation. LeuTech avidly binds to circulating and sequestered human polymorphonuclear neutrophils in vivo, eliminating in vitro cell labeling and blood handling. METHODS: We studied 49 patients to evaluate the safety and efficacy of LeuTech imaging. 99mTc-labeled LeuTech was prepared on site using a lyophilized kit, 99mTc-labeled pertechnetate, and 2 different incubation techniques, 1 at room temperature and the other at 37 degrees C. The abdomen was serially imaged for up to 3 h after the intravenous administration of 370-740 MBq 99mTc-labeled LeuTech. Scans were read as positive or negative for acute appendicitis or other intraabdominal infection. The institutional diagnosis was established by surgery, other diagnostic studies, or 1-mo clinical follow-up. RESULTS: Scans were positive for appendicitis in all 26 patients with appendicitis, for a sensitivity of 100%, and negative for appendicitis in 19 of 23 patients without appendicitis, for a specificity of 83%. Accuracy, positive predictive value, and negative predictive value were 92%, 87%, and 100%, respectively. Results were not different between the LeuTech preparations. The rate of laparotomies with negative findings in patients who underwent surgery was 10%. The average time from injection to LeuTech visualization in the appendix for cases positive for appendicitis was 9 min. No serious adverse reactions occurred. CONCLUSION: LeuTech imaging is safe, rapid, and sensitive for diagnosis of appendicitis in equivocal cases. The potential advantages of LeuTech over currently available radiopharmaceuticals for infection imaging are ease of preparation, absence of blood handling, excellent image quality, no requirement for SPECT, and rapid diagnostic uptake.

The role of radiolabeled leukocyte imaging in the management of patients with acute appendicitis.

Acute appendicitis is a clinically challenging surgical disease particularly difficult to diagnosis in women and children. An atypical presentation of acute appendicitis is a major factor leading to delay in diagnosis and unnecessary surgery. Delay in diagnosis is associated with morbidity from perforation, abscess and prolonged hospitalization. The routine use of adjunctive imaging studies has not improved the diagnostic accuracy for acute appendicitis nor has impacted clinical outcome. 99mTc HMPAO-labeled leukocyte imaging is one diagnostic imaging test that has the potential of altering the clinical management of acute appendicitis. 99mTc HMPAO-labeled leukocyte imaging is highly sensitive for detecting even small inflammatory processes in the abdomen because of high target to background and early rapid uptake at sites of inflammation. We studied the use of 99mTc HMPAO-labeled leukocytes for diagnosis and management of suspected acute appendicitis in 124 patients with an atypical clinical presentation. Emergent imaging was performed immediately following injection of labeled leukocytes and continued until positive or through 2 hours if negative. The scan correctly and rapidly detected acute appendicitis in 50 of 51 patients with surgical confirmation for a sensitivity of 98%. The specificity was 82% leading to an overall accuracy of 90%. The high negative predicted value of 98% allowed early discharge from the emergency department and avoided costly observation in the hospital and potentially unnecessary surgery in these patients with negative scans. The negative exploratory laparotomy rate was 4% in this patient population compared to 9% in a similar population of patients who were not scanned. These data have been confirmed now in over 600 patients scanned in our department. The main drawbacks of 99mTc HMPAO-labeled leukocyte imaging are the requirement of blood handling and a delay in diagnosis because of the 2-hours preparation time prior to imaging. There are new radiopharmaceuticals on the horizon which have the potential of replacing 99mTc HMPAO-labeled leukocyte imaging and offer advantages of a shorter preparation time and no blood handling. These include 99mTc labeled monoclonal antibodies and chemotactic peptides. The 99mTc anti-SSEA-1 IgM antibody (LeuTech) is currently under investigation for use in acute appendicitis. In summary, nuclear medicine can play a key role in the diagnosis of acute appendicitis in patients with an atypical presentation. This technique is cost effective and appears to impact favorably on clinical outcome.

99mTc-hexamethylpropyleneamine oxime (Tc-WBC) scan for diagnosing acute appendicitis in children.

We used a radiolabeled white blood cell (WBC) scan as an adjunct to diagnose appendicitis in 100 children with equivocal signs or symptoms of appendicitis. WBC separation and labeling took 2 hours. Patients were imaged up to 3 hours after injection of labeled Tc-WBC. Accuracy was established in all 100 children by histopathological findings, medical records and follow-up interviews. Scans were positive in 40 and negative in 60. Positive scans averaged 76 +/- 40 minutes after injection (mean +/- SD); negative scans required 150-180 minutes. Tc-WBC scan correctly identified appendicitis in 36 of 37 children (sensitivity, 97%) and correctly excluded appendicitis in 59 of 63 (specificity, 94%). The false negative scan occurred in a patient whose perforated appendix was discovered at operation 3 days following the scan. Accuracy of the examination was 95 per cent, with a positive predictive value of 90 per cent and a negative predictive value of 98 per cent. The negative laparotomy rate for the entire group was 4 per cent. Tc-WBC imaging is an accurate, noninvasive test for ruling out appendicitis in children with right lower quadrant abdominal pain and equivocal presentation, although positive scans require more clinical judgment. The high sensitivity and negative predictive value suggest its potential for screening and discharging children from the emergency department.

Tc-99m-HMPAO white blood cell scan for diagnosis of acute appendicitis in patients with equivocal clinical presentation.

OBJECTIVE: The authors' goal was to evaluate the accuracy of Technetium 99m-HMPAO-labeled leukocyte imaging for screening patients with atypically presenting appendicitis and to determine how availability of this test affected practice patterns of surgeons at the authors' medical center. SUMMARY BACKGROUND DATA: Appendicitis can be difficult to diagnose and in equivocal cases usually requires inpatient observation. The delay may increase morbidity and costs. A test that rules out acute appendicitis could be cost effective if it allowed early discharge from the emergency department. Previously, there have been no simple, rapid, accurate noninvasive methods for improving diagnostic accuracy in patients with equivocal presentations of appendicitis. METHODS: Patients referred to rule out appendicitis were analyzed. Patients were imaged up to 3 hours after injection of 10-mCi 99mTc-HMPAO-labeled autologous leukocytes (Tc-WBC), and when the scans became positive, imaging was terminated and the requesting physician notified of the results. Diagnostic accuracy was established by surgical and histopathologic findings or by absence of symptoms after 1 month clinical follow-up. The source of referral, hospital length of stay, disposition of patients, and ancillary tests (ultrasound, computed tomographic scan, and barium enema) were analyzed. RESULTS: One hundred twenty-four patients were studied from November 1991 through December 1995. Fifty-eight percent of positive scans showed uptake within 1 hour of injection and 73% by 2 hours. The Tc-WBC scan correctly identified an inflammatory source of abdominal pain in 65 of 66 cases (sensitivity = 98%) and was correctly negative in 55 of 58 cases (specificity = 95%). The scan correctly diagnosed appendicitis in 50 of 51 cases (sensitivity = 98%) and correctly excluded appendicitis in 62 of 73 cases (specificity = 85%). Outpatient referrals increased from 38% to 87%. In those patients with negativescans, inpatient observation, number of adjunctive tests, and length of stay decreased significantly. CONCLUSIONS: The high sensitivity and negative predictive value of Tc-WBC imaging may permit patients to be screened and discharged from the emergency department. Focally positive scans often indicate disease requiring operation but not in all cases. The Tc-WBC imaging reduced the negative laparotomy rate to 3.9% while reducing admission rates and hospital length of stay.

Gold-195m first-pass radionuclide ventriculography, thallium-201 single-photon emission CT, and 12-lead ECG stress testing as a combined procedure.

Graded, sequential, rest/exercise, gold-195m (Au-195m) (T1/2 = 30 seconds), first-pass ventriculography and thallium-201 (T1-201) single-photon emission computed tomography (SPECT) were performed simultaneously during a single, electrocardiograph-monitored, bicycle stress test in 24 individuals. The technical aspects and logistics involved in performing this combined radionuclide study are stressed in this preliminary report. Fourteen healthy volunteers each had a normal left ventricular ejection fraction and wall-motion response, along with normal Tl-201 perfusion and washout, as determined by both visual and quantitative analysis of the tomographic sections. Each of ten patients with coronary artery disease had at least one abnormality of these parameters. We suggest that it is technically feasible to evaluate both cardiac function and myocardial perfusion simultaneously by combining Au-195m ventriculography and T1-201 SPECT imaging into a single, noninvasive, diagnostic package.

In-111-leukocyte scintigraphy for detection of infection associated with peritoneal dialysis catheters.

In-111-labeled leukocytes were administered to 13 patients on continuous ambulatory peritoneal dialysis in order to locate catheter-associated infections. Using a marker to indicate the catheter exit site, infections of the catheter tunnel were correctly identified prior to surgery in 4 patients with relapsing peritonitis and infections of the exit site were diagnosed in 5 out of 7 patients. There were no false positives or negatives as documented by surgery or follow-up. The authors conclude that In-111-leukocyte scintigraphy appears to be accurate in diagnosing peritoneal infections of the dialysis catheter tunnel.