Bifunctional antibody: a binary radiopharmaceutical delivery system for imaging colorectal carcinoma.

In clinical studies we have evaluated a unique monoclonal antibody-based drug delivery system, a bifunctional antibody designed to deliver imaging or therapeutic agents, such as radioisotopes, drugs, or biologics, to tumor cells, while minimizing the dose to normal tissue. The bifunctional antibody, with one specificity to a tumor-associated antigen (carcinoembryonic antigen) and another specificity to a hapten, is injected and allowed to localize at a tumor site for 4 days. A hapten, tagged with a radioisotope, is subsequently injected for delivery to and capture by the prelocalized antibody at the tumor site. In studies reported here, the sulfhydryl groups of Fab' fragments of ZCE-025 and CHA-255 were linked with bis-maleimidomethyl ether to form an F(ab')2 bifunctional antibody coupled by a stable thioether linkage. EOTUBE, a hydroxyethylthiourido derivative of benzyl EDTA, was used as the hapten carrier of 111In. Fourteen patients 62-82 years old with recurrent or metastatic adenocarcinoma of the colon were studied. Twenty of 21 known lesions were imaged, and eight of nine new lesions were confirmed. With this fundamentally new approach to drug delivery, clearance from normal tissue is rapid, and high tumor:normal tissue ratios are expeditiously achieved.

Skeletal scintigraphic changes in osteoporosis treated with sodium fluoride: concise communication.

An appendicular skeletal response to sodium fluoride (NaF) was detected by total skeletal scintigrams. Twelve postmenopausal osteoporotic women were treated with NaF (88 mg/day) and calcium (1500 mg/day). Total skeletal scintigrams were obtained before and during treatment. Within 4 to 21 mo (mean: 8.3), all 12 patients showed new areas of increased uptake corresponding to metaphyseal regions and short bones of the appendicular skeleton. The number of peripheral bones involved in each subject ranged from four to 12. The most frequently involved sites (11 of 12 patients) were the right distal femur and proximal tibia. Nine patients showed an increase in serum alkaline phosphatase activity, which was attributed to an increase in the skeletal isoenzyme. Seven of 12 patients developed bone pain in one or more of the regions of increased uptake. This study establishes that the skeletal scintigram is a sensitive index of the peripheral skeletal response to NaF.

Particulate myocardial perfusion scintigraphy: its clinical usefulness in evaluation of coronary artery disease.

The determination of myocardial viability is a crucial parameter in the evaluation of a patient with coronary artery disease. Particulate myocardial perfusion scintigraphy (PMPS) is one of several methods available for this determination. A brief comparison between PMPS and two other commonly used methods is described in this review. The technique and analysis are described and applied to 194 patients with 366 surgically bypassed regions. The patients are analyzed for postoperative regional wall function and for total ventricular function as expressed by ejection fraction. PMPS is a highly accurate and unique study for clinically predicting myocardial viability.

The pitfalls of technetium Tc 99m/thallium 201 parathyroid scanning.

Technetium Tc 99m/thallium 201 parathyroid scanning has been proved to be effective by multiple researchers. A review of 54 patients who underwent scanning and operations at an institution showed the scans to be accurate in 83%. There were 15% false-negative and 2% false-positive scans. The pitfalls of parathyroid scanning can be related to false-positives and false-negatives.

Parathyroid imaging.

Radionuclide scanning for hyperparathyroidism is an accurate cost-effective preoperative test that can provide the basis for more effective surgery.

Post-laryngectomy localization of I-131 at tracheostomy site on a total body scan.

A post-thyroidectomy, post-I-131-therapy patient had a laryngectomy and neck dissection for recurrent papillary thyroid carcinoma. A subsequent I-131 total body scan revealed persistent anterior neck activity, which disappeared upon removal of the tracheostomy tube and dressings.

Usefulness of SPECT in evaluating osteosarcoma metastases to the lung.

The differentiation of osteosarcoma metastases to the lung vs the ribs with bone scanning agents is not always clear. Single photon emission computed tomography is useful in such differentiation.

Nuclear medicine-important advances in clinical medicine: the role of nuclear and ultrasonic thyroid imaging.

The Scientific Board of the California Medical Association presents the following inventory of items of progress in nuclear medicine. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, research workers or scholars to stay abreast of these items of progress in nuclear medicine that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another.The items of progress listed below were selected by the Advisory Panel to the Section on Nuclear Medicine of the California Medical Association and the summaries were prepared under its direction.

Enhancement of monoclonal antibody binding to melanoma with single dose radiation or hyperthermia.

We undertook this study to determine whether radiation (10 Gray, single dose) or water bath hyperthermia (41 degrees C, 45 min) could enhance binding of 111In-labeled anti-p97a monoclonal antibody (MAb) to human melanoma tumors transplanted subcutaneously into nude mice. Sixty animals were given injections of 1-2 X 10(7) Brown C5513 melanoma cells. At 1-2 weeks postinjection, two-thirds of the mice were treated (one-third served as controls). Within 3 hours after treatment, each animal was given iv 2 muCi 111In-anti-p97a MAb. At 24 and 48 hours thereafter, whole-body scans were done with the use of a MaxiCamera 300 A/M unit, and the ratio of activity at the tumor and liver was determined. Some animals were kept for 7 days posttreatment, whereas others were taken after the 48-hour scan for determination of biodistribution of the radiolabeled complex. Enhancement of MAb binding was demonstrated by either modality, although enhancement was more consistent with radiation. The therapeutic efficacy of MAb may be enhanced with increased binding of radioactive MAb complexes through single dose radiation or hyperthermia.

Relationship between ZCE 025 blood clearance and liver accumulation in patients with colorectal cancer.

Clinical interest in radiolabelled monoclonal antibodies (mAbs) derives from their ability to target tissues and deliver radioisotopes thereto. Diagnostic and therapeutic trials suggest that the potential of mAbs would be optimized with better understanding of factors which influence blood clearance. This study sought to advance that understanding. Nine colon cancer patients were injected with 20 mg 111In radiolabelled ZCE 025 mAb, then laser-positioned and imaged daily for one week via nuclear medicine views. Laser-positioned CT images were also obtained, enabling image registration. Blood samples were taken at 30, 60, and 90 min and at every imaging time point. Sample activity was plotted to estimate the elimination half-life (t1/2 beta). Liver radiation dose was calculated from the images and evaluated for total organ (mCi-h) and region of interest (microCi-h/g). Laboratory values and patients' physical parameters were also studied to determine their impact on liver uptake and mAb blood clearance. Liver radiation dose, as measured in this study, correlated with terminal half-life of the mAb in blood; patients' liver enzymes and physical parameters did not. Radioactivity in a 48-h or 72-h blood sample correlates with t1/2 beta and liver radiation dose, suggesting that a single 72-h sample can predict both.