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.

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.

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.

Clonidine and glucose intolerance.

Changes in carbohydrate metabolism were observed in a diabetic, hypertensive patient managed with clonidine. After a slight increase in the clonidine dose, his blood sugar control deteriorated. However, when the clonidine was withdrawn, the glucose intolerance subsided. Because clonidine preferentially binds alpha 2-subtype receptors, we investigated animal pancreatic tissue by radioligand binding technique and found it to contain alpha-adrenergic receptors predominantly of the alpha 2-subtype. In consideration of the response from withdrawal of clonidine and the results of our radioligand studies, wer concluded the glucose intolerance seen in this patient was most likely due to the specific action of clonidine on alpha 2-pancreatic receptors.