Use of Sulesomab, a radiolabeled antibody fragment, to detect osteomyelitis in diabetic patients with foot ulcers by leukoscintigraphy.

Diabetic patients suspected of having osteomyelitis secondary to foot ulcers underwent scintigraphic imaging with Sulesomab, an anti-granulocyte antibody Fab' fragment labeled with technetium-99m. Among 122 patients who had osteomyelitis confirmed or excluded by histopathologic and/or microbiologic techniques, Sulesomab had a 91% sensitivity, a 56% specificity, and an accuracy of 80%. One planar imaging session was usually sufficient for diagnosis, typically requiring 20-30 minutes of camera time 1-2 hours after injection. Compared with ex vivo autologous white blood cell (WBC) scans, Sulesomab performed comparably but with significantly greater sensitivity (92% vs. 79%; P < .05). Sulesomab results were more sensitive than radiography (90% vs. 62%; P < .05) and more specific than bone scans (50% vs. 21%; P < .05) and would have altered management plans in most patients. No related adverse events occurred, and there was no induction of human anti-mouse antibody. Sulesomab is an effective and rapid imaging agent that is diagnostically comparable or superior to WBC scans in this setting, with significant advantages in safety and ease of use.

Comparative study of monoclonal antibody scan in diagnosing orthopaedic infection.

When clinical data are insufficient to diagnose infection of bone or joints, nuclear scanning becomes crucial in making an accurate diagnosis. The efficacy of (99m)technetium antigranulocyte monoclonal antibody Fab' fragment (LeukoScan) is prospectively compared with (111)indium white blood cell and (99m)technetium methylene diphosphonate bone scans in 74 patients with suspected musculoskeletal infections. They were grouped according to site of suspected infection: 33 long bones, 23 prosthetic joints, and 18 diabetic feet. Sixty-two of these 74 patients had surgical verification with histopathology or culture. The remaining 12 patients had clinical followup as proof of absence of infection. The overall sensitivity of LeukoScan, (111)indium white blood cell, and (99m)technetium methylene diphosphonate bone scans was 93%, 85% and 92%, respectively. Specificity was 89%, 75% and 52%, and accuracy was 90%, 79% and 74%, respectively. The conclusion from this study is that LeukoScan is more accurate in detecting osteomyelitis, with better sensitivity and specificity in prosthetic joints. Compared with (111)indium white blood cell scans, LeukoScan++ gives superior images, and results are obtained in 1 to 6 hours without biohazard risk from handling blood products.

Haemodialysis during cardiopulmonary bypass using a haemofilter.

The decision to employ haemofiltration and/or haemodialysis is based on various criteria depending on institutional protocol. Cardiac surgical patients, especially those with renal failure, often require fluid and electrolyte intervention. In the past haemodialysis patients were closely monitored and often delayed for surgery depending on their electrolyte status. Operative technique was changed to accommodate the impending sequelae of cardioplegic solutions, blood transfusions and fluid administration. Although haemofiltration has been used successfully in the management of hypervolaemia and anaemia due to haemodilution, the rate of uraemic toxins and solute removal may not be adequate. The use of haemodialysis helps in the treatment of these difficult and often unpredictable cases. The type of dialysate and method of administration has simplied the technique of haemodialysis, during CPB, allowing effective solute and toxin removal while being able to control the amount of fluid removed.

Use of technetium antigranulocyte monoclonal antibody Fab' fragments for the detection of osteomyelitis.

Accurate early diagnosis of osteomyelitis is critical for optimal clinical management. Conventional radiology (X-rays, CT) and nuclear medicine scans (bone, gallium, and technetium/indium white blood cell [WBC]) have limitations and drawbacks. The monoclonal antibody (MAb) ImmuRAID-MN3 (Immunomedics Inc., Morris Plains, NJ), a 99m-Tc Antigranulocyte Fab' fragment, recognizes a surface glycoprotein NCA-90/95 shared by granulocytes, carcino-embryonic antigen (CEA), and meconium antigen (MA). Intravenous injection of radiolabeled MAb enables in vivo labeling of human granulocytes and targets infected lesions in the bone and throughout the body. Technetium labeled Fab' fragments rapidly clear the blood pool and high-quality images can be obtained the same day, as early as 1 h postinjection. Results at our institution on 13 patients with clinically suspected osteomyelitis of infected long bones, prostheses, and diabetic foot ulcers were compared with the surgical/bacteriological verification of the presence or absence of infection. The MAb scan showed six true positives, six true negatives, and one false negative (very low grade infection). The procedure was safe, no clinical or laboratory adverse reactions were encountered. The MAb fragments are markedly less immunogenic than whole IgG, resulting in lower induction of human antimouse antibody (HAMA) titers. No HAMA to this MAb fragment has been detected in 24 patients (data from multiple institutions). Our preliminary results suggest that 99m-Tc ImmuRAID-MN3 is highly accurate for detection of osteomyelitis. This study is part of an ongoing multiinstitutional project sponsored by Immunomedics, Inc. to evaluate the efficacy and safety of this radiopharmaceutical.

Immunoscintigraphy performed with In-111-labeled CYT-103 in the management of colorectal cancer: comparison with CT.

Immunoscintigraphy performed after intravenous administration of indium-111-labeled CYT-103, an immunoconjugate of monoclonal antibody B72.3, was evaluated in patients with suspected primary or recurrent colorectal cancer at 25 centers in the United States. Gamma camera imaging, computed tomography (CT), and confirmatory surgical exploration were completed in 169 of 227 patients who received single infusions of In-111 CYT-103. Eight patients (3.5%) had reversible, nonserious adverse reactions, and 39% developed antimurine antibodies. Surgery revealed that 155 of 169 patients had colorectal carcinoma. In these 155 patients, immunoscintigraphy and CT demonstrated similar sensitivity (69% and 68%, respectively) and specificity (77%). However, immunoscintigraphy had greater sensitivity in detection of pelvic tumors (74% vs 57%, P = .035) and extrahepatic abdominal tumors (66% vs 34%, P less than .001); CT enabled detection of a greater proportion of liver metastases (84% vs 41%, P less than .001). These results indicate that In-111 CYT-103 can be administered safely and that immunoscintigraphy performed with this agent frequently enables identification of extrahepatic abdominal sites of disease not visualized with CT.

Functional studies of left upper quadrant mass aid management of idiopathic thrombocytopenic purpura.

ITP (idiopathic thrombocytopenic purpura) causes rapid sequestration and destruction of thrombocytes by the spleen, liver, bone marrow, and reticuloendothelial elements of other organs. The usefulness of multiple radionuclide functional imaging procedures in the management of a 34-year-old woman with chronic ITP, two splenectomies (removal of the initial spleen and then a hypertrophied accessory spleen), and the failure of chemotherapy to control her thrombocytopenia, are discussed. A combination of In-111 oxine autologous platelet imaging, liver/spleen imaging, disofenin (liver/gallbladder) imaging, and glucoheptonate renal imaging demonstrated that her platelets were being sequestered by a markedly enlarged left hepatic lobe extending to the left lateral wall, with a small amount in the kidneys and lungs, and that there was no second accessory spleen.

Pharmacokinetics of indium-111-labeled B72.3 monoclonal antibody in colorectal cancer patients.

Mean time parameters provide a new approach to plasma pharmacokinetics of radiolabeled Mabs that may show important patient differences affecting diagnosis or treatment. We determined mean time pharmacokinetic parameters for 11 patients entered in a Phase I/II clinical trial for detection of colorectal cancer. Patients were administered 0.5-2 mg of B72.3 anti-TAG-72 radiolabeled with 3.5-5 mCi of 111In, plasma activity was measured over time. Mean time pharmacokinetic parameters were (mean +/- s.e.m.): mean residence time; body (MRTB) 88.9 +/- 7.2 hr, central (MRTC) 73.8 +/- 6.0 hr; mean transit time, central (MTTC) 41.1 +/- 9.0 hr; mean residence time, periphery (MRTP) 15.1 +/- 3.4 hr; intrinsic mean residence time, periphery (IMPTP) 39.0 +/- 7.6 hr; mean transit time, periphery (MTTP) 24.0 +/- 6.7 hr; probability of distribution (PRD) 50% +/- 10%; and n compartmental cycles of 4.54 +/- 2.3 times. In patients with increased circulating specific TAG-72 antigen, MRTC greater than MTTC and n much greater than 1. In patients without specific antigen, MRTC approximately equal to MTTC and n much less than 1. Pharmacokinetic studies may identify patients who do not have the tumor produced target antigen for the specific Mab and may provide an opportunity to select another specific Mab with an increased chance for successful diagnosis or treatment.

Human biodistribution of 111In-labeled B72.3 monoclonal antibody.

The murine IgG1 monoclonal antibody B72.3 reacts with human colorectal, breast, lung, pancreatic, gastric, and ovarian tumors. Human biodistribution studies using intact 131I-B72.3 have been reported by Carrasquillo et al. (J. Nucl. Med., 29: 1022-1030, 1988). We have performed similar studies on five patients using i.v. infusion of 20 mg of intact 111In-B72.3 (Cytogen Corp.). Serum clearance is similar with a t1/2 of 64.2 h (range, 44-80) for 111In-B72.3 and 65 h (range, 32-106) for 131I-B72.3 (J. A. Carrasquillo et al., J. Nucl. Med., 29: 1022-1030, 1988). However, organ biodistribution is markedly different. For 131I-B72.3, hepatic and splenic clearance mirrors blood pool clearance (J. A. Carrasquillo et al., J. Nucl, Med., 29: 1022-1030, 1988). For 111In-B72.3, there is rapid uptake in tumor, liver, spleen, kidney, lumbar spine, and testes by 2-6 h with no significant clearance over the next 9 days. For 111In-B72.3, quantitative analysis of liver (from biopsy specimens), spleen, kidney, and lumbar spine (from scintiphoto regions of interest after background subtraction and attenuation correction) shows the following peak organ biodistributions in percentage infused dose: liver, 32%; spleen, 3.9%; kidneys, 3.5%; and lumbar vertebral bodies (marrow sample), 2.7%. For both 111In-B72.3 and 131I-B72.3, the principal route of excretion from the body is urinary with excretion rate of 131I faster than 111In. The marked differences between 111In-B72.3 and 131I-B72.3 biodistribution and clearance strongly influence the dosimetry, immunodetection, and immunotherapeutic potentials of B72.3 MoAb.

SPECT gallium scanning for lymphoma and infection.

Thirty gallium scans, using currently acceptable dosage levels (5-6 mCi) and a conventional rotating gamma camera, were performed on 20 patients with lymphoma or infection. Compared to planar scans, SPECT increased sensitivity and lesion detection from 48% to 89% in lymphoma, and from 50% to 80% in infection. The predictive value of a negative site was 81% in lymphoma and 67% in infection. Gallium utility is markedly increased by SPECT imaging. A normal gallium SPECT scan is highly accurate in ruling out disease.

Relationship of creatinine clearance to orthoiodohippurate measured effective renal plasma flow.

Effective renal plasma flow (ERPF) was measured utilizing 1-131 orthoiodohippurate (OIH). The OIH ERPF was correlated in 50 patients with routine 24-hour urine creatinine clearance measurements and with a formula predicting creatinine clearance based on age, weight, and serum creatinine (formula creatinine clearance). The filtration fraction (routine creatinine clearance/OIH ERPF) in 38 patients with hypertensive nephrosclerosis, tubulointerstitial renal disease, or normal renal function were compared. Filtration fractions in the three groups tested were not statistically different. ERPF had a correlation coefficient of 0.62 with routine creatinine clearance and 0.72 with formula creatinine clearance. Thus, OIH ERPF correlates with creatinine clearance measurements but cannot be used to replace creatinine clearance as a method of evaluating renal function. The reasons for the lack of a stronger positive correlation between ERPF and glomerular filtration rate (GFR) remain to be elucidated.

Detection of fetal anencephaly using real-time ultrasound.

Anencephaly can be diagnosed using real-time ultrasonography. This enables visualization of the fetal movements and facilitates identification of the fetal parts, making certain the exact orientation of the fetus. Thus, the negative finding of the lack of fetal calvarium, as well as the positive finding of insufficient space for a calvarium to exist between the fetal thorax and the uterine wall, can be confidently ascertained. One can then be certain that a fetal head is not being missed by the ultrasound beam, as is possible with a rapidly moving fetus using B-mode ultrasound.

Splenic visualization using 99mTc-methylene diphosphonate in a patient with sickle cell disease.

Splenic visualization with a bone-seeking agent 99mTc-methylene diphosphonate (99mTc-MDP) with absence of splenic uptake using sulfur colloid was seen in a 15-year-old boy in sickle cell crisis. Uptake of 99mTc-MDP is probably due to splenic infarction and calcification. This represents a potentially sensitive method for following the functional auto-splenectomy process in sickle cell disease and may also detect the presence of splenic tissue when it is not visualized in a sulfur colloid liver/spleen scan. Splenic visualization by bone-seeking agents should not be confused with skeletal lesions or indicate the presence of an abnormal left upper quadrant mass lesion.

Reference values based on hospital admission laboratory data.

Laboratory values taken from more than 13,000 newly admitted patients to the University of Alabama Hospital were analyzed using a percentile ranking system, and histograms for 24 laboratory tests were prepared. The percentile system is a better way to express test results than the classic normal range. The ability to correlate a test result with a clinical problem rises proportional to the degree of deviation from the midrange. Minor deviations frequently are without explanation, even after intensive clinical investigation. Invariably, great deviations are explainable. If one limits the interpretation of results to three ranges--abnormally low, abnormally high, and normal--much of the value of laboratory test interpretation is lost.

Grey scale ultrasonography: evaluating the jaundiced patient.

Over a period of one year, 75 patients with jaundice were evaluated by grey scale ultrasonography. Intravenous cholangiography was attempted in 26 instances (bilirubin value greater than 4.3 mg/100 ml) and was diagnostic in only four. Ultrasound, on the other hand, was diagnostic for surgical jaundice in 62 of the 75 cases (82%). In 52 of the 62 patients a cause for the extrahepatic obstruction was demonstrated: 40 had cholelithiasis and choledocholithiasis, and 12 had tumors (11 pancreatic tumors, one lymphoma). In the remaining ten instances, obstruction was sonographically demonstrated but the cause was not. Of these, four patients were subsequently proven to have distal common duct stones, five had carcinoma of the pancreas and one had cholangiocarcinoma. This evidence indicates that ultrasound should be the noninvasive procedure of choice in the clinical assessment of obstructive jaundice.

Creatine phosphokinase isoenzyme fractions in the serum of a patient struck by lightning.

Serial creatine phosphokinase (CPK) isoenzyme determinations were taken in an 8-year-old boy whose being struck by lightning resulted in prolonged cerebral anoxia, inferolateral myocardial infarction and death. All three isoenzyme levels (CPK-MM, CPK-MB, and CPK-BB) were elevated. The CPK-BB isoenzyme level increase was transient, being very high three hours postlightning strike and disappearing at approximately 24 hours.