lewis-x-antigen and Appendicitis

LeuTech is a sterile, lyophilised kit-packaged diagnostic system containing murine anti-CD15 IgM monoclonal antibody proprietary radiolabelled with technetium 99m ((99m) Tc) for infection imaging. After intravenous injection of LeuTech, diagnostic imaging can be obtained within 1h with conventional planar gamma camera techniques. LeuTech binds to neutrophils in vivo at the infection site. LeuTech is a fast (1h to obtain image), convenient (one-step injection), safe, effective (bright, clear images) and cost-effective diagnostic for existing and new nuclear imaging markets including chronic and acute indications such as appendicitis, ischaemic bowel, post-surgical infection and nosocomial infection. Palatin Technologies has successfully completed a Phase III trial with LeuTech in 203 patients at 10 sites in the USA for the detection of equivocal appendicitis. A BLA with the US FDA for LeuTech has been filed for the diagnosis of equivocal appendicitis. The US FDA has recommended LeuTech for approval for the diagnosis of appendicitis in patients with equivocal signs and symptoms. On 28 September 2000 Palatin received a 'complete review' letter from the FDA regarding the BLA for LeuTech. While, there were no further data requested on the safety and clinical efficacy of LeuTech, FDA requested some manufacturing, quality control and validation steps and data to be completed prior the approval of LeuTech. Palatin plans to finalise the amendments to BLA in the H2 of 2002. LeuTech is also being investigated in Phase II clinical trials for the diagnosis of osteomyelitis in 45 patients at four sites. Positive interim results from a Phase II clinical study conducted in 19 patients with diabetic foot ulcers and suspected osteomyelitis were announced at the Society of Nuclear Medicine Annual Meeting, Toronto, Canada, in June 2001. Imaging with LeuTech provided a diagnostic image within 1 hour compared with the 24 hours required to obtain an image using standard-of-care diagnostic, Indium oxide-labelled white blood cells. Walter Reed Army Medical Center is evaluating LeuTech for early detection of inhalation anthrax. LeuTech is planned to be evaluated for the detection of osteomyelitis secondary to joint replacements (such as hip replacement), postoperative abscesses, ulcerative colitis and other intra-abdominal infections (colitis, spleen or urinary tract). Palatin Technologies has exclusive rights to murine anti-CD15 IgM monoclonal antibody from The Wistar Institute o

Topics: Acute Disease; Antibodies, Monoclonal; Appendicitis; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Freeze Drying; Gamma Cameras; Humans; Inflammation; Lewis X Antigen; Radionuclide Imaging; Reagent Kits, Diagnostic; Technetium

Appendicitis frequently presents in an atypical fashion leading to misdiagnosis or a delay in diagnosis. This is particularly true in early cases where the patient may be erroneously discharged from an emergency department and will invariably return with perforated appendicitis. The standard of care is hospital admission for observation or early operation. Adjunctive imaging tests have been used with mixed results in this equivocal patient population. The authors studied a promising new monoclonal antibody, 99mTc-labeled anti-CD 15 (LeuTech; Palatin Technologies, Inc., Princeton, NJ), which specifically targets neutrophils and may be used for imaging appendicitis. This prospective, multicenter, open-label study evaluated the diagnostic efficacy and clinical impact of LeuTech scintigraphy for detecting appendicitis in patients with an equivocal presentation.. A total of 200 patients (121 females, 79 males; age range 5-86 years; mean age 30.5 +/- 16.5 years) completed the study. Management plan was formulated before and reassessed following LeuTech imaging to determine impact on management. Following intravenous injection of LeuTech, the abdomen was imaged with a standard gamma camera for 30 to 90 minutes.. Fifty-nine patients had a histopathologic diagnosis of acute appendicitis. LeuTech identified 53 of 59 patients with appendicitis (90% sensitivity) and was negative in 122 of 141 patients without appendicitis (87% specificity). Accuracy, positive predictive value, and negative predictive value were 88%, 74%, and 95%, respectively. Diagnostic efficacy was unchanged in a subgroup of 48 pediatric patients (5-17 years). Diagnostic images for appendicitis were achieved within 8 minutes postinjection in 50% of patients and within 47 minutes in 90% of patients. Significant shifts in patient management decisions were evident following LeuTech results. LeuTech was well tolerated with no serious adverse events reported.. LeuTech is a convenient, safe, rapid, and sensitive imaging test for diagnosis of appendicitis and favorably impacts patient management in adult and pediatric patients with equivocal signs and symptoms.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Appendicitis; Child; Female; Humans; Lewis X Antigen; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Radionuclide Imaging; Technetium

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.

Topics: Adult; Animals; Antibodies, Monoclonal; Appendicitis; Bone Diseases; False Negative Reactions; Female; Humans; Infections; Lewis X Antigen; Lung Diseases; Male; Mice; Middle Aged; Predictive Value of Tests; Radiopharmaceuticals; Reference Values; Reproducibility of Results; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

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.. 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.. 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.. 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.

Topics: Acute Disease; Adult; Animals; Antibodies, Monoclonal; Appendicitis; Female; Humans; Isotope Labeling; Lewis X Antigen; Male; Mice; Neutrophils; Radioimmunodetection; Radiopharmaceuticals; Sensitivity and Specificity; Sodium Pertechnetate Tc 99m

Topics: Acute Disease; Animals; Antibodies, Monoclonal; Appendicitis; Emergency Service, Hospital; Humans; Lewis X Antigen; Mice; Radioimmunodetection; Radiopharmaceuticals; Sodium Pertechnetate Tc 99m

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.

Topics: Abdomen; Abdominal Pain; Acute Disease; Antibodies, Monoclonal; Appendectomy; Appendicitis; Follow-Up Studies; Humans; Immunoglobulin M; Injections, Intravenous; Lewis X Antigen; Neutrophils; Predictive Value of Tests; Radioimmunodetection; Radiopharmaceuticals; Safety; Sensitivity and Specificity; Technetium Tc 99m Exametazime

Topics: Antibodies, Monoclonal; Appendicitis; Clinical Trials as Topic; Humans; Lewis X Antigen; Radioimmunodetection; Reagent Kits, Diagnostic; Technetium