BACKGROUNDDuring the process of bone cement joint replacement, some patients show a series of complications, such as a sudden drop in blood pressure or dyspnea. The cause of the complication is considered to be due to emboli caused by the femur prosthesis insertion. The purpose of the present study was to detect the pulmonary embolism in rabbits after bone cement perfusion by radioimmunoimaging, and to explore its protective measures.

METHODSForty rabbits, 2.5 - 3.0 kg weight, were randomly assigned to four groups, with ten rabbits in each group. Group I (no intervention): Bone cement perfusion was done after medullary cavity reaming and pressurizing. Group II (epinephrine hydrochloride intervention): The medullary cavity was rinsed with a 1:10 000 normal saline-diluted epinephrine hydrochloride solution followed by bone cement perfusion after medullary cavity reaming and pressurizing. Group III (fibrin sealant intervention): The medullary cavity was precoated with fibrin sealant followed by bone cement perfusion after medullary cavity reaming and pressurizing. Group IV (blank control group): The medullary cavity was not perfused with bone cement after reaming. In each group, the rabbits underwent femoral head resection and medullary cavity reaming. Before bone cement perfusion, 2 ml of developing tracer was injected through the ear vein. Radionuclide imaging was performed at 60, 120, and 180 minutes after bone cement perfusion, and the pulmonary radioactivity in vivo was measured. The rabbits were immediately sacrificed, and the pulmonary tissue was removed and its radioactivity was measured in vitro. Pulmonary tissue was then fixed and the pulmonary embolism and the associated pathological changes were observed.

RESULTSThe pulmonary radioactivity in vivo was measured at 60, 120, and 180 minutes after bone cement perfusion. The radioactivities of the four groups were 11.67 ± 2.16, 14.59 ± 2.92 and 18.43 ± 4.83 in group I; 8.37 ± 3.05, 10.35 ± 2.24 and 11.48 ± 2.96 in group II; 3.91 ± 1.19, 5.53 ± 2.95 and 7.25 ± 1.26 in group III; 1.04 ± 0.35, 1.14 ± 0.87 and 1.43 ± 0.97 in group IV. The radioactivities of groups I, II, III at 60, 120 and 180 minutes were significantly higher than group IV (P < 0.05). The pulmonary embolism could be detected. Pretreatment with epinephrine hydrochloride and fibrin sealant significantly decreased the pulmonary radioactivity in group II and group III, but it was still higher than in the group IV.

CONCLUSIONSRadioimmunoimaging is an alternative method for the dynamic observation of rabbit pulmonary embolism after bone cement perfusion. Radioimmunoimaging is the optional way to evaluate the effect of pretreatment with epinephrine hydrochloride or fibrin sealant on pulmonary embolism after bone cement perfusion.

Animals ; Bone Cements ; Pulmonary Embolism ; diagnosis ; Rabbits ; Radioimmunodetection ; methods

PURPOSE: Radiolabeled CEA79.4 antibody has a possibility to be used in radioimmunoscintigraphy or radioimmunotheraphy of cancer. We investigated the in vitro properties and biodistribution of CEA79.4 antibody labeled with Re-188 or Tc-99m. MATERIALS AND METHODS: CEA79.4 was reduced by 2-mercaptoethanol to produce-SH reside, and was labeled with Re-188 or Tc-99m. For direct labeling of Tc-99m, methylene-diphosphonate was used as transchelating agent. CEA79.4 in 50 mM Acetate Buffered Saline (ABS, pH 5.3) was labeled with Re-188, using stannous tartrate as reducing agent. In order to measure immunoreactivity and the affinity constant of radiolabeled antibody, cell binding assay and Scatchard analysis using human colon cancer cells SNU-C4, were performed. Biodistribution study of labeled CEA79.4 was carried out at 1, 14 and 24 hr in ICR mice. RESULTS:. Labeling efficiencies of Tc-99m and Re-188 labeled antibodies were 92.4+/-5.9% and 84.7+/-4.6%, respectively. In vitro stability of Tc-99m-CEA79.4 in human serum was higher than Re-188-CEA79.4. Immunoreactivity and affinity constant of Tc-99m-CEA79.4 were 59.2% and 6.59x109 M-1, respectively, while those of Re-188-CEA79.4 were 41.6% and 4.2x109 M-1, respectively. After 24 hr of administrations of Re-188 and Tc-99m labeled antibody, the remaining antibody, the remaining antibodies in blood were 6.32 and 9.35% ID/g respectively. The biodistribution of each labeled antibody in other organs was similar because they did not accumulate in non-targeted organs. CONCLUSION: In vitro properties and biodistribution of Re-188-CEA79.4 were similar to those of Tc-99m-CEA79.4. It appears that Re-188-CEA79.4 can be used as a suitable agent for radioimmunotherapy.
Animals ; Antibodies ; Colonic Neoplasms ; Humans ; Hydrogen-Ion Concentration ; Mercaptoethanol ; Mice ; Mice, Inbred ICR ; Radioimmunodetection ; Radioimmunotherapy

The aim of this research is to prepare a novel monoclonal antibody against granulocytes by the intraperitional routine procedure and evaluate the usefulness of (99)Tc(m) labelled anti-granulocyte monoclonal antibody (McAb) SZ-102 for the detection of experimental inflammatory areas in rabbits. It was characterized as IgG1 subclass by the double immunodiffusion analysis. The flow cytometry demonstrated that SZ-102 reacted selectively with human granulocytes, monocytes, and with their bone marrow precursors, while human lymphocytes, red blood cells and platelets remained negative. In addition, SZ-102 antigen was expressed on the macrophages of liver, lung, thymus, spleen and lymph node by immunohistochemical SP methods. It is suggested that McAb SZ-102 is mainly against granulocytes. SZ-102 was labelled with (99)Tc(m) using 2-iminothiolane modification McAb and (99)Tc(m) -glucoheptonate (GH) transchelation method. The experimental rabbit model of inflammatory areas was prepared,through injecting with (99)Tc(m)-SZ-102 by ear-edge vein, and then imaged by SPECT. (99)Tc(m) labelled murine IgG was used as a negative control. The inflammatory areas in rabbits were clearly imaged at 2 to 4 hour after injection of (99)Tc(m)-SZ-102, while the control group after injection of (99)Tc(m)-labeled murine IgG was negative. In conclusion, the McAb SZ-102 may be a potential agent for the diagnosis and localization of inflammatory areas of carcinomas and clinically concealed infectious diseases.
Animals ; Antibodies, Monoclonal ; Flow Cytometry ; Granulocytes ; immunology ; Humans ; Inflammation ; diagnostic imaging ; Mice ; Mice, Inbred BALB C ; Rabbits ; Radioimmunodetection ; Technetium

Nuclear oncolgy is important in the diagnosis, staging, and long-term surveillance of a number of cancers. Over the past 10 years there has been an explosion of new radioisotopic tracers aimed at detecting, staging and eventually treating tumors. Clinicians and oncologists can now use specific radiolabeled metabolic tracers, monoclonal antibodies, and molecular probes based on the sequencing of the human genome. The current applications of positron emission tomography (PET) in oncology have included characterizing tumor lesions, differentiating recurrent disease from treatment effects, staging tumors, evaluating the extent of disease, and monitoring therapy. The future developments in medicine may use the unique capabilities of PET not only in diagnostic imaging but also in molecular medicine and genetics. Radioimmunoscintigraphy is a technique which uses radiolabeled antibodies to visualize tumors, taking advantage of antigens preferentially expressed by malignant tissue. However, the implementation of radiolabeled antibodies as "magic bullets" for detection and treatment of diseases such as cancer has required addressing several shortcomings of murine monoclonal antibodies. Genetic engineering provides a powerful approach for redesigning antibodies for use in oncologic applications in vivo. Recently, noninvasive molecular imaging has been developed. Most current molecular imaging strategies are "indirect" and involve the coupling of a "reporter gene" with a complementary "reporter probe". Imaging the level of probe accumulation provides indirect information related to the level of reporter gene expression. In this article, the author discuss the current status of PET, radioimmunoscintigraphy, gene imaging and receptor imaging with a brief review on nuclear oncology.
Antibodies ; Antibodies, Monoclonal ; Diagnosis ; Diagnostic Imaging ; Explosions ; Genes, Reporter ; Genetic Engineering ; Genetics ; Genome, Human ; Humans ; Molecular Imaging ; Molecular Medicine ; Molecular Probes ; Nuclear Medicine* ; Positron-Emission Tomography ; Radioimmunodetection

OBJECTIVETo establish a two-step pretargeting approach to lymphoma radioimmunoimaging in mice using biotinynaled CD45 monoclonal antibody (McAb) and (188)Re-avidin in a tumor-bearing mouse model.

METHODSSix Nod-Scid mice bearing lymphoma cell xenograft were randomized to receive either an intravenous injection of 50 µg/200 µL biotinyled CD45 McAb followed 24 h later by an intraperitoneal injection of 3.7 MBq (50 µg/100 µL) (188)Re-avidin (two-step pretargeting group), or a single intravenous injection of 3.7 MBq (100 µg/100 µL) (188)Re-CD45 McAb (control group). SPECT was performed at 0.5, 1, 6 and 23 h post-injection to characterize (188)Re isotope biodistribution. At 24 h pos-injection, the mice were sacrificed for measurement of radioactivity uptake in the tumor and normal tissues and calculation of the tumor-to-non-tumor (T/NT) ratios.

RESULTSSPECT showed that the two-step pretargeting method resulted in a low radioactivity in the blood pool during the imaging and a concentrated radioactivity in the liver and spleen. The transplanted tumor began to be displayed at 1 h post-injection and was clearly displayed at 1-6 h; the images were clear even at 23 h. With the two-step pretargeting method, the radioactive uptake at 24 h post-injection were (1.34∓0.52)%, (6.77∓2.32)%, and (2.81∓1.25)% in the tumor, kidney and liver, respectively, with low radioactivity levels in other organs and high tumor/blood and tumor/muscle ratios (4.28∓0.82 and 8.00∓0.88, respectively). In the control group, SPECT revealed intense radioactivity in the liver, spleen, and kidneys with obscure display of the tumor; at 20 h, the radioactivity in the blood pool remained high but that in the tumor was low, and the tumor/blood and tumor/muscle ratios at 24 h were only 0.58∓0.06 and 3.21∓0.24, respectively.

CONCLUSIONCompared with (188)Re-CD45 McAb, the two-step pretargeting approach exhibits a good specificity in targeting lymphoma with an increased T/NT ratio in mice and allows early tumor display at 1 h post-injection.

Animals ; Antibodies, Monoclonal ; Avidin ; Disease Models, Animal ; Lymphoma ; diagnosis ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Radioimmunodetection ; Tissue Distribution ; Tomography, Emission-Computed, Single-Photon

To study bioadhesive property of carbomer 934 in dog alimentary tract, carbomer 934 and ethylcellulose were radiolabelled with technetium-99 m. The gastrointestinal emptying rate of these materials was measured by the technique of gamma scintiscan. The results showed that the empty rate of adhesive material (carbomer 934) was remarkably slower in dog alimentary tract compared to nonadhesive material (ethylcellulose). It is concluded that, in dog, the interaction between gastrointestinal mucus layer and adhesive material or nonadhesive material was significantly different. Carbomer 934 had stronger bioadhesive property in vivo than that of ethylcellulose.
Acrylic Resins ; pharmacokinetics ; Animals ; Cellulose ; analogs & derivatives ; pharmacokinetics ; Digestive System ; diagnostic imaging ; Dogs ; Gamma Cameras ; Gastric Emptying ; Intestinal Mucosa ; metabolism ; Radioimmunodetection

OBJECTIVETo study the mechanism of cardiotoxicity associated with Herceptin.

METHODSHerceptin was labeled with iodine-131 using the Iodogen method. Radioimmunoimaging was performed in 5 rabbits at 3 h to 5 days following (131)I-Herceptin injection to investigate the biodistribution of Herceptin. (131)I-Herceptin uptake in each organ or tissue relative to that in the muscular tissue (O/M ratio) was calculated and compared. On the fifth day following the injection, the organs including the heart, lung, liver and muscles were taken for measurement of the weight and radiocounts. HER2 expression was measured by immunohistochemistry in these organs and tissues.

RESULTSThe O/M ratio of the heart was significantly higher than that of the lung (P=0.032) and liver (P=0.019) at 3 h after Herceptin injection, but reduced significantly at 24 h (P=0.001). The uptake of (131)I-Herceptin in the myocardium was slightly higher that that in the muscle and intestine, but lower than that in the lung and spleen. HER2 expression showed no significant difference between the myocardium and the other tissues such as the liver, lung, and kidney (H=3.236, P=0.172).

CONCLUSIONMyocardium expresses low levels of HER2 and accumulates Herceptin no more than the other tissues.

Animals ; Antibodies, Monoclonal ; administration & dosage ; pharmacokinetics ; toxicity ; Antibodies, Monoclonal, Humanized ; Female ; Iodine Radioisotopes ; administration & dosage ; pharmacokinetics ; Male ; Myocardium ; metabolism ; Rabbits ; Radioimmunodetection ; Receptor, ErbB-2 ; metabolism ; Tissue Distribution ; Trastuzumab

PURPOSE: This prospective study was performed to evaluate the usefulness of preoperative radioimmu-noscintigraphy and intraoperative scintimetric examination (radioimmunoguided surgery: RIGS) using (99m)Tc-anti-CEA F(ab')(2), fragment. MATERIALS AND METHODS: Nineteen patients with rectal cancer underwent preoperative whole body planar scintigraphy at 4 hours after injection of (99m)Tc-anti-CEA F(ab')(2), fragment and SPECT imaging at 18 hours. Surgical operation was performed at 24 hours after injection. During laparotomy, radioactivities from intraabdominal viscera were measured by gamma probe. The radioac-tivities from excised tumor and lymph nodes were also measured and compared with pathology. RESULTS: All nineteen patients were confirmed to have adenocarcinomas in the rectum. Twenty-seven of 97 excised lymph node groups had metastasis and 2 patients had liver metastasis in pathology. Preoperative radioim- munoscintigraphy detected primary tumors in 11 patients (sensitivity 55%) and it couId not detect any lymph nodes or liver metastasis. All patients showed high radioactivity in the kidneys, liver, spleen, and major vessels in intraoperative measurement by gamma probe, and tumor activity was not discriminated from background activity. However, ra4ioactivity from excised tumor was higher than normal rectum (T/B ratio; 3.47+/-2.25). When excised lymph node activity/background activity ratio > 1,5 was considered as positive criteria of metastasis, sensitivity, specificity, positive and negative predictive values were 78.6%, 73.9%, 55.0% and 89.5%, respectively. CONCLUSION: Radioimmunoscintigraphy using (99m)Tc-anti-CEA F(ab')(2). has no additional value for preoperative staging and use of early RIGS using (99m)Tc-anti-CEA F(ab')(2)is inappropriate. For early RIGS using (99m)Tc labeled antibodies in rectal cancer patients, further development of more specific antibodies and methods to reduce background activity are needed.
Adenocarcinoma ; Antibodies ; Humans ; Kidney ; Laparotomy ; Liver ; Lymph Nodes ; Neoplasm Metastasis ; Pathology ; Pilot Projects* ; Prospective Studies ; Radioactivity ; Radioimmunodetection* ; Radionuclide Imaging ; Rectal Neoplasms* ; Rectum ; Sensitivity and Specificity ; Spleen ; Tomography, Emission-Computed, Single-Photon ; Viscera

BACKGROUNDMonoclonal antibodies (mAbs) such as DD3, raised against progastrin-releasing peptide(31-98) (ProGRP (31-98)) antigen, have been used to target small cell lung cancer (SCLC). However, as an intact mAb, DD3 is cleared slowly from the body, with an optimal radioimmunoimaging time of 72 hours. More recently, a single-chain antibody fragment has demonstrated reduced excretion time in blood and normal tissues and is increasingly used in diagnostic cancer research. Thereby, it potentially increases the radioimmunoimaging efficacy. However, there have been few studies with this antibody fragment. The aim of this study was to characterize the preliminary radioimmunoimaging and biodistribution of (131)I-anti-ProGRP(31-98) scFv in nude mice bearing SCLC xenografts.

METHODSAnti-ProGRP(31-98) scFv was used to detect ProGRP expression by flow cytometry analysis and immunohistochemistry. (131)I-anti-ProGRP(31-98) scFv was injected intravenously into healthy Kunming mice and the percentage injected dose per gram (%ID/g) in various organs was calculated. Similarly, the %ID/g and tumor/non-tumor ratio in xenograft-bearing mice was calculated. After injection of (131)I-anti-ProGRP(31-98) scFv, treated mice were imaged at 1, 24, and 30 hours. Then the tumor/base ratios were calculated.

RESULTSProGRP was highly expressed in NCI-H446 cells and xenograft tissue. The metabolism of (131)I-anti-ProGRP(31-98) scFv in healthy mice was consistent with a first-order and two-compartment model; T1/2α and T1/2β were 10.2 minutes and 5 hours 18 minutes, respectively. The %ID/g of (131)I-anti-ProGRP(31-98) scFv in xenografts was much higher than in healthy tissues at 12 hours after injection, reaching a maximum of (5.38±0.92) %ID/g at 24 hours. Successful imaging of xenograft tissue was achieved as early as 1 hour post-injection and persisted until 30 hours, with 24 hours proving optimal.

CONCLUSION(131)I-anti-ProGRP(31-98) scFv shows highly selective tumor uptake with low accumulation in normal tissues and rapid blood clearance, indicating that it could be a promising agent for SCLC radioimmunoimaging.

Animals ; Female ; Flow Cytometry ; Humans ; Immunoglobulin Fragments ; immunology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Peptide Fragments ; immunology ; Radioimmunodetection ; methods ; Recombinant Proteins ; immunology ; Small Cell Lung Carcinoma ; diagnostic imaging ; metabolism ; Xenograft Model Antitumor Assays