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PubMed1994

Indium-111-labeled anti-EGFr-425 scintigraphy in the detection of malignant gliomas.

BACKGROUND: The monoclonal antibody anti-epidermal growth factor receptor (EGFr) antibody-425, against the epidermal growth factor receptor, has the potential to bind specifically to gliomas and not normal brain tissue. A prospective study was conducted (1986-1988) to evaluate the use of Indium-111 (111In)-labeled anti-EGFr-425 in the localization of gliomas before radioimmunotherapy with Iodine-125 (125I)-labeled anti-EGFr-425. METHODS: Twenty-eight patients with intracranial neoplasms were injected intravenously with an average dose of 2.2 mCi 111In-labeled anti-EGFr-425. Planar and single-photon emission computed tomography scans were performed after 48 and 72 hours. Control studies also were performed in two cases with 111In-labeled Co 17-1A (an antibody to colorectal cancer) and in one case with unlabeled 111In chloride. RESULTS: The immunoscintigraphic findings were generally in good agreement with computerized tomographic findings. The definitive diagnosis was established by biopsy findings: 23 gliomas (1 Grade I, 5 Grade II, 6 Grade III, and 11 Grade IV), 1 meningioma, and 4 metastatic lesions. The localization of gliomas with 111In-labeled anti-EGF-425 had a sensitivity of 0.96, a specificity of 0.60 and an accuracy of 0.90. CONCLUSION: Immunoscintigraphy with 111-In labeled anti-EGFr-425 can be useful in the management of malignant gliomas, especially before radioimmunotherapy with 125I-labeled anti-EGFr-425.

Adult↗
PubMed1994

Immunoscintigraphy in cancer care.

Despite numerous publications on the ability of immunoscintigraphy to detect recurrent gastrointestinal and ovarian tumors much earlier than other diagnostic methods currently used in the postoperative follow-up, this method has still not received the clinical recognition it deserves. This is due to multiple factors, but mostly to the lack of well designed multicenter trials intended to assess the large scale efficacy of the method. The cost-benefit approach might be helpful in designing such studies.

Clinical Trials as Topic↗
PubMed1994

A new fiducial alignment system to overlay abdominal computed tomography or magnetic resonance anatomical images with radiolabeled antibody single-photon emission computed tomographic scans.

BACKGROUND: The use of computed tomography (CT) or magnetic resonance (MR) to overlay or register uptake patterns displayed by single-photon emission computed tomography (SPECT) with specific underlying anatomy has the potential to improve image interpretation and decrease diagnostic reading errors. The authors have developed a method that will allow the selection of a region of interest on MR or CT images that correlates with SPECT antibody images from the same patient. This method was validated first in phantom studies and subsequently was used on three patients with suspected colorectal carcinoma. METHODS: Two patients were injected with the technetium-99m-labeled 88BV59 immunoglobulin G human antibody, and the third patient was injected with the iodine-131-labeled 16.88 immunoglobulin M human antibody. CT or MR scans were obtained before antibody infusion, and subsequent SPECT scans were obtained on the first or fourth day after infusion. A customized body cast with landmarks was used for each patient during the CT, MR, and SPECT scans to match slice positions for all scanning modalities. Corresponding fiducial landmarks were identified on axial images. A computer graphics program was written to match and overlay corresponding landmarks for each imaging modality. The image registration accuracy was measured by comparing fiducial marker separations (center to center) on the registered scans. This separation uncertainty was 1-2 mm for CT-MR and 3-4 mm for CT-SPECT phantom studies. RESULTS: For patient studies, the fiducial alignment uncertainty was 3-4 mm for axial CT-SPECT and MR-SPECT images, and 6-8 mm for sagittal CT-SPECT and MR-SPECT images. The accuracy of the anatomic alignment of the patient and image registration system was +/- 1 cm in the medial-lateral axis and +/- 2 cm in the cranial-caudal direction. CONCLUSIONS: This type of image analysis may resolve uncertainties with the anatomic correlation of SPECT images that otherwise may be regarded as questionable when SPECT is used alone for radioimmunodiagnosis.

Colorectal Neoplasms↗
PubMed1994

Small animal imaging with pinhole single-photon emission computed tomography.

BACKGROUND: High resolution spatial details of the distribution of activity in three dimensions is required to evaluate the localization and dosimetric properties of radiolabelled monoclonal antibodies in tumors and normal tissues. Planar imaging of small animals with a resolution of 5-10 mm is usually the imaging modality of choice. The authors investigated high resolution single-photon emission computed tomographic (SPECT) imaging, based on a rotating pinhole scintillation camera. Although the sensitivity of the pinhole collimator is low, several radionuclides offer suitable decay properties to perform pinhole SPECT, especially in conjunction with high activity levels used in radioimmunotherapy. METHODS: Transverse, sagittal, and coronal sections were reconstructed using a three-dimensional cone-beam algorithm, which is a generalization of the two-dimensional fan-beam filtered backprojection algorithm. Before reconstruction, the pinhole projections were corrected for the decay of the radionuclide, geometric and intrinsic efficiency variations of the camera system, and center of rotation shift. RESULTS: The spatial resolution at 50 mm from the pinhole collimator with 3.3 mm aperture was 3.4 mm, and the sensitivity 7.2 c/s microCi for technetium-99m. With the 2 mm collimator the resolution was 2.2 mm, and the sensitivity was 2.6 c/s/microCi. To show the spatial resolution in vivo, a rat was injected with 185 MBq of technetium-99m-methylene diphosphonate or with 5 mCi technetium-99m-hexamethylpropylene amine oxime. The bone structures were well delineated in the methylene diphosphonate image, and in the hexamethylpropylene amine oxime image, the brain was nicely shown. For comparison a magnetic resonance image for the same section was done. CONCLUSIONS: High resolution SPECT imaging with the pinhole collimator provides mapping of the activity in three-dimensions, needed for more detailed biodistribution data and to perform more accurate dosimetry.

Algorithms↗
PubMed1995

The significance of intraoperative periportal lymph node metastasis identification in patients with colorectal carcinoma.

BACKGROUND: Nine patients who underwent Radioimmunoguided Surgery (RIGS) (Neoprobe Corporation, Dublin, OH) procedures for colorectal cancer were found to have disease recurrence in the periportal area. This led to a retrospective study to determine whether periportal lymph node involvement could have been predicted intraoperatively for these patients. METHODS: One hundred twenty-four patients underwent second-look RIGS for recurrent colon and rectal cancer from 1986 to 1992. The monoclonal antibody (MAb) B72.3 was administered as the carrier agent to 87 patients and the CC49 second-generation MAb was administered to 37 patients. Both MAbs were radiolabeled with Iodine-125. RESULTS: Periportal lymph nodes with RIGS-positive tissue were found in 47 (38%) patients, hematoxylin and eosin-positive lymph nodes were found in 13 of 47, and in further immunohistochemical studies performed for 31 of the remaining 34 patients, positive lymph nodes were found in 8, resulting in an incidence of 48% (21/44). A critical review of the nine patients' charts who later presented with a tumor mass in the periportal area demonstrated intraoperative gamma-detecting probe counts in ratios three to five times that of the normal adjacent tissues in the periportal area at the time of first exploration. Probe-directed biopsy was reported to be histologically negative for tumor in these patients, and, thus, the surgeon proceeded assuming the periportal area to be negative. A retrospective study of the periportal lymph nodes of these patients using cytokeratin immunohistochemical analysis identified tumor in five (56%). CONCLUSIONS: These findings suggest that the RIGS system may be a valuable method of intraoperative prediction and detection of periportal lymph node metastasis.

Antibodies, Monoclonal↗
PubMed2000

Radioimmunoguided surgery for recurrent colorectal cancer manifested by isolated CEA elevation.

BACKGROUND: Carcinoembryonic antigen (CEA) is a sensitive marker for detecting recurrent colorectal carcinoma. An asymptomatic rise of CEA can precede by several months the detection of recurrent cancer by standard imaging modalities. Yet, surgeons are hesitant to operate solely on the basis of an observed increase in CEA. We investigated the ability of radioimmunoguided surgery to enhance the surgeon's capability of detecting intraabdominal disease in these patients. METHODS: Nineteen patients who underwent radioimmunoguided surgery for suspected tumor recurrence based solely on elevated CEA were included in the study. They underwent colonoscopy and CT of the abdomen and chest, all of which were negative. They then underwent scintigraphy scan with an anti-CEA monoclonal antibody (MoAb) labeled with (99m)Tc or Indium I-111. All patients were injected with the CC49 MoAb (an anti-TAG-72 tumor-associated glycoprotein) labeled with (125)I three weeks before surgery. During surgery, traditional exploration was followed by survey with a gamma-detecting probe. RESULTS: Traditional surgical exploration identified 26 recurrent tumors: 7 hepatic, 8 pelvic, 6 retroperitoneal, 3 colonic, 1 splenic, and 1 anastomotic. Radioimmunoguided surgical exploration confirmed all recurrent tumors and identified additional tumor sites in seven patients that resulted in changing the surgical plan. CEA scans correlated with intraabdominal findings in seven patients. Abdominal pathology did not correlate completely with the scans in three patients, and CEA scan results were undetermined in two patients. CONCLUSION: Patients with elevated CEA and no other findings should be operated upon without delay, and radioimmunoguided surgery should be used to enhance the surgeon's knowledge of the extent of disease.

Adult↗
PubMed2000

A therapeutic human anti-idiotypic antibody mimics CD55 in three distinct regions.

The human anti-idiotypic antibody 105AD7 was isolated from a colorectal cancer patient receiving the anti-tumor antibody 791T/36 for radioimmuno-scintigraphy of liver metastases. We have mapped the binding site of 791T/36 to the first two small consensus repeat (SCR) domains of the complement regulatory protein (CD55) that is overexpressed by a wide range of solid tumors. Cloning of both antigen and anti-idiotype has identified the molecular basis of their mimicry. Amino acid homology has been identified between three complementarity-determining regions of 105AD7 and three regions of CD55 within the first two SCR domains. 791T/36 and anti-anti-idiotypic (Ab3) polyclonal antibodies raised against 105AD7 showed specific binding to these peptides. The antibodies were also found to bind synergistically to combinations of these peptides, indicating cooperativity between the peptides in stabilizing antibody binding. This also implies that the contact face on both CD55 antigen and 105AD7 is generated by the cooperation of several peptides positioned on two domains in each protein. Thus a human monoclonal anti-idiotypic antibody generated by a cancer patient is able to show both amino acid and structural homology with the complement regulatory protein CD55. These findings help identify the mechanism by which a human anti-idiotypic antibody is able to mimic a tumor-associated antigen and stimulate anti-tumor B and T cell responses.

Adenocarcinoma↗
PubMed2002

Targeted radiotherapy with [(90)Y]-SMT 487 in mice bearing human nonsmall cell lung tumor xenografts induced to express human somatostatin receptor subtype 2 with an adenoviral vector.

BACKGROUND: Novel approaches to increasing the therapeutic efficacy of targeted radiotherapy of cancer are required. One strategy to achieve this goal is to induce high-level expression of a receptor on the surface of tumor cells that can be targeted with a radiolabeled peptide. The objectives of this study were to 1) induce somatostatin receptor (SSTr2) expression in tumor cells using an adenovirus encoding the SSTr2 gene (AdSSTr2), 2) demonstrate tumor localization of [(111)In]-DTPA-D-Phe(1)-octreotide in AdSSTr2-injected tumors, and 3) show therapeutic efficacy with [(90)Y]-DOTA-D-Phe(1)-Tyr(3)-octreotide ([(90)Y]-SMT 487). METHODS: SSTr2 expression was validated in vitro by the binding and subsequent internalization of [(111)In]-DTPA-D-Phe(1)-octreotide (21.3% per mg of total protein) in A-427 cells infected with AdSSTr2. In vivo imaging confirmed 5- to 10-fold greater uptake 5.5 hours after intravenous administration of [(111)In]-DTPA-D-Phe(1)-octreotide in AdSSTr2-injected tumors relative to control tumors. For therapy studies, mice bearing established subcutaneous A-427 tumors were given two intratumoral injections of AdSSTr2 1 week apart, followed by an intravenous injection of 400 microCi or 500 microCi [(90)Y]-SMT 487 at 2 and 4 days after each adenoviral administration. Control animals either were not treated or were administered 500 microCi [(90)Y]-SMT 487 with no AdSSTr2 injection. RESULTS: These studies showed that untreated animals and animals treated with no virus and 500 microCi [(90)Y]-SMT 487 had median tumor quadrupling times of 16 and 25 days, respectively. Mice administered AdSSTr2 and either 400 microCi or 500 microCi of [(90)Y]-SMT 487 demonstrated significantly longer median tumor quadrupling times of 40 and 44 days, respectively (P < 0.02). CONCLUSIONS: These studies are the first to demonstrate in vivo therapeutic efficacy using a radiolabeled peptide targeted to a receptor expressed on the surface of tumor cells following gene transfer. Future studies will focus on the optimization of this approach.

Adenoviridae↗
PubMed1993

Monoclonal antibodies in the management of ovarian cancer. A clinical perspective.

Despite recent advances in the conventional management of ovarian cancer, this disease remains the leading cause of death among the gynecologic malignancies, killing more American women each year than all other gynecologic cancers combined. As a tumor arising from a nonessential organ that remains primarily confined to the peritoneal cavity, ovarian cancer makes an attractive target for monoclonal antibodies (MoAb). Several MoAb have been developed that have actual or potential clinical use in the management of ovarian cancer. Serum assays using a MoAb against an ovarian cancer-associated antigen (CA 125) are currently in routine clinical use for monitoring the course of disease in women with known ovarian cancer. Such assays may play a role in multitechnique screening programs. Radiolabeled antibodies are under study for use in external imaging or intraoperative detection of ovarian cancer. Isotope-labeled antibodies also are being evaluated in the treatment of ovarian cancer as are antibodies coupled to drugs or biologic toxins. Some antibodies may have direct antitumor effects through binding to biologically active receptors or through immune effector functions. The use of antibody fragments, chimeric antibodies, human antibodies, and genetically engineered antibodies is under active investigation. MoAb have important potential for improving the diagnosis, monitoring of response to therapy, and treatment of ovarian cancer.

Antibodies, Monoclonal↗
PubMed2004

Perfusion of 99Tcm-labeled CD105 Mab into kidneys from patients with renal carcinoma suggests that CD105 is a promising vascular target.

There is strong published and unpublished evidence that our CD105 Mab E9, which is highly reactive with angiogenic endothelial cells, could be a useful reagent to target the vasculature of solid tumors in man. Since Mab E9 does not cross-react with animal tissues, we undertook here to evaluate its localization using human kidney as an ex vivo model. Perfusion was performed through the renal artery of 99Tcm-labeled purified CD105 Mab in freshly excised kidneys from 7 patients with renal carcinoma. In all 7 cases, immunoscintigraphs showed the presence of well-defined radioactive hot spots, which matched the positions of the tumors as identified by presurgery MRI scans and subsequent histopathologic examination. Importantly, in one instance, where a presurgery MRI scan had identified only one tumor, immunoscintigraphs showed 2 distinct hot spots of radioactivity. The pathology report confirmed that the additional hot spot corresponded to a small secondary well-vascularized tumor. The implication of this finding is that the radiolabeled Mab, E9, may be of use in the detection of metastatic disease. That the labeling of tumors was specific was confirmed when prior perfusion of unlabeled mab E9 in 2 kidneys completely blocked the localization of 99Tcm-conjugated Mab E9. Radioactivity in samples of tumor and normal tissue taken from 7 kidneys was counted in a gamma counter. In all cases, there was a greater uptake of radioactivity in tumors compared with the corresponding normal kidneys. The median values, adjusted per gram wet weight, for 99Tcm were 14.8 times (range, 4.8-113.0) greater in kidney tumors than in normal kidney tissue (p < 0.007). Immunofluorescent staining of cryostat sections of tumor tissues in each of the 7 cases showed strong and uniform localization of Mab E9 in tumor microvessels. Interestingly, chimeric staining of endothelial cells (ECs) was seen in an occasional microvessel segment. That is, while most of the ECs lining a microvessel were strongly stained, an occasional EC was negative. This was not an artifact of staining. Unstained ECs may be nonangiogenic or apoptotic since CD105 is a proliferation/activation-associated antigen. Further investigations are warranted to establish the pharmacokinetics of 99Tcm-labeled CD105 antibody in vivo. This would enable us to determine whether an apparently highly successful ex vivo study has the potential for tumor imaging/therapeutic vascular targeting in patients with cancer.

Antibodies, Monoclonal↗
PubMed2002

Enhancement of colorectal tumor targeting using a novel biparatopic monoclonal antibody against carcinoembryonic antigen in experimental radioimmunoguided surgery.

Biparatopic CEA, carcinoembryonic antigen (MAb) was newly designed and tested as to whether it enhanced the accuracy of tumor detection by reducing non-specific binding in experimental radioimmunoguided surgery. Biparatopic MAb was prepared by using cross-linking of reduced Fab' fragments from PR1A3 and T84.66. Fifty-nine tumors from 2 human colorectal carcinoma cell lines with high (KM-12c) and low (Clone A) carcinoembryonic antigen (CEA) expression were successfully implanted subcutaneously on the backs of 42 nude mice. Tumors were localized using 125I-labeled MAbs: IgG, F(ab')(2) and Fab' of PR1A3, and biparatopic MAb of PR1A3 and T84.66. Radioactivity counted on a portable radioisotope detector correlated well with that counted on a gamma counter (p < 0.001). Accumulations of radioactivity in control mice without tumorigenesis were the greatest in PR1A3 IgG-pretreated mice and the least in biparatopic MAb-pretreated mice. Tumors of 2 cell lines did not differ in the distribution of radiolabeled MAbs. Localization indices of the tumor in various organs revealed 1.3 to 4.1 in PR1A3 IgG-pretreated mice, 2.4 to 6.6 in fragment MAbs of PR1A3-pretreated mice and 2 to 4.6 in biparatopic MAb-pretreated mice. Silver grains and immune staining were predominantly distributed in tumor cells of all types of MAb-pretreated mice. Sensitivity and specificity of tumor localization by radioimmunoguided surgery (RIGS) were the highest in the biparatopic MAb-pretreated mice (90.9% and 94.5%, respectively) and the least in the PR1A3 IgG-pretreated mice (50% and 72%). The biparatopic MAb using 2 anti-CEA MAbs against different epitopes achieved a great affinity and avidity with accurate localization of colorectal carcinoma in experimental radioimmunoguided surgery.

Adenocarcinoma↗
PubMed1991

Improvement by affinity chromatography on antiidiotypic monoclonal antibodies (MAbs) of immunoreactivity and in vivo targeting of radiolabelled anti-HMW-MAA MAb TP61.5 in nude mice bearing human melanoma lesions.

The human high-molecular-weight melanoma-associated antigen (HMW-MAA) represents a useful marker for immunoscintigraphy in patients with melanoma. Since injection of a radiolabelled anti-HMW-MAA monoclonal antibody (MAb) visualizes only about 60% of melanoma lesions, approaches are being developed to increase the sensitivity of immunoscintigraphy. One of them aims at improving the immunoreactivity of radiolabelled anti-HMW-MAA MAbs, since this approach may improve the targeting of radiolabelled MAbs to melanoma lesions. We have previously shown that affinity chromatography on insolubilized anti-idiotypic MAbs is a useful method for purifying immunoreactive anti-HMW-MAA MAb TP61.5 from 125I-labelled MAb preparations and that not all the anti-idiotypic MAbs are useful for this purpose. Since the increasing number of available anti-idiotypic MAbs is likely to facilitate the application of this procedure in many antigenic systems, we have now tested criteria to select anti-idiotypic MAbs suitable for the purification procedure. Furthermore, we have investigated the effect of the increase in immunoreactivity of 125I-MAb TP61.5 on its in vivo targeting to human melanoma lesions transplanted into nude mice. Among the 3 anti-idiotypic MAbs tested, the most effective in purifying immunoreactive MAb TP61.5 molecules following radiolabelling is MAb TK7-110, with which 125I-MAb TP61.5 displays an immunoreactivity similar to that displayed with melanoma cells. This parameter may represent a useful criterion to identify anti-idiotypic MAbs suitable for the purification procedure, if the present results are confirmed with a large number of anti-idiotypic MAbs in different antigenic systems. We have also shown that an incubation time for up to 4 hr of 125I-MAb TP61.5 with insolubilized MAb TK7-110 is the most effective in increasing immunoreactivity and in recovering immunoreactive MAb applied to the affinity matrix. The increase in the immunoreactive fraction of 125I-MAb TP61.5 significantly increases its specific localization in human melanoma lesions transplanted into nude mice. These results suggest that purification of radiolabelled immunoreactive anti-HMW-MAA MAb TP61.5 by affinity chromatography using anti-idiotypic MAb TK7-110 represents a useful approach to increasing the sensitivity of immunoscintigraphy in patients with melanoma.

Animals↗
PubMed1992

Human carcinoembryonic antigen cDNA expressed in rat carcinoma cells can function as target antigen for tumor localization of antibodies in nude rats and as rejection antigen in syngeneic rats.

We have tried to develop a new model consisting of rats transplanted with syngeneic colon carcinoma PROb cells transfected with cDNA coding for the carcinoembryonic antigen (CEA), the human tumor marker most commonly used as target for MAbs. The antigenic density of the 4 CEA-expressing clones selected for a precise characterization ranged from 5 x 10(4) to 1 x 10(6) CEA molecules per cell. In all clones the CEA was shown to be attached to the membrane by a phosphatidylinositol (PI) anchor. Using a panel of radiolabeled MAbs directed against the 5 major epitopes described on the CEA molecule, we showed that all these CEA epitopes were expressed by the 4 transfectants. Southern-blot analysis showed that the entire CEA cDNA was present in the transfectants. Western-blot analysis, however, showed that the size of the CEA expressed by the 4 transfectants was slightly smaller than that of CEA produced by 2 reference human colon-carcinoma cell lines. Two clones, expressing 1 x 10(5) and 1 x 10(6) CEA molecules per cell, respectively, were grafted s.c. in nude mice and rats. Injection of radiolabeled anti-CEA F(ab')2 fragments into these animals showed specific tumor localization with the highest percentages of injected doses for the transfectants expressing the highest CEA level. When grafted into immunocompetent syngeneic BDIX rats, the CEA-expressing clones induced a strong antibody response against CEA and tumor rejections in a majority of the animals. Although the analysis of the immune response against the CEA-cDNA-transfected carcinoma cells is under investigation, the present results demonstrate that human CEA could function as a rejection antigen when transfected into rat carcinoma cells.

Adenocarcinoma↗
PubMed1994

A comparison of 67Cu- and 131I-labelled forms of monoclonal antibodies SEN7 and SWA20 directed against small-cell lung cancer.

The intact anti-SCLC monoclonal antibody (MAb) SEN7 and its F(ab')2 were labelled with the beta-emitting isotope 67Cu. Both materials retained their biological activity in vitro as determined by the Lindmo assay. In a direct comparison of in vivo distribution in a xenograph model, 131I- and 67Cu-labelled intact SEN7 showed similar absolute tumour accumulation. Blood levels were markedly lower in the case of the 67Cu-labelled antibody, resulting in improved tumour:blood ratios which reached a maximum of 13:1 compared with only 4.5:1 for 131I-SEN7. In the case of the 67Cu-labelled F(ab')2, very high accumulation of the nuclide was observed in the kidney. Levels of radio copper in liver and spleen were also found to be significantly raised when compared with radio iodine. SWA20, a MAb which had previously failed to show any selective in vivo accumulation in tumour xenografts when labelled with radio iodine showed higher and more stable tumour accumulation when labelled with 67Cu.

Animals↗
PubMed2002

Non-invasive imaging of vulnerable plaques by molecular targeting of oxidized LDL with tagged oxidation-specific antibodies.

The concept of the "vulnerable" plaque has recently emerged to explain how quiescent atherosclerotic lesions evolve to cause clinical events. Vulnerable plaques are generally non-obstructive, asymptomatic lesions that may abruptly rupture and induce thrombotic occlusion leading to tissue ischemia and its attendant sequelae. They are responsible for over 50% of cases of sudden death and acute myocardial infarction. The lipid component of vulnerable plaques, which is abundant and highly enriched in oxidized low-density lipoprotein (OxLDL), strongly contributes to their propensity to rupture through physical, inflammatory, and thrombogenic properties. We hypothesized that OxLDL would serve as an ideal target to detect vulnerable plaques. In a series of experimental studies, we have shown that oxidation-specific antibodies (Ox-AB) specifically accumulate in vivo within lipid-rich atherosclerotic lesions but not normal arteries, provide a quantitative measure of the content of OxLDL, allow detection of atherosclerosis progression and regression in the context of enhanced or reduced OxLDL content and non-invasively image atherosclerotic lesions. Ox-AB may be tagged with appropriate labels for use in nuclear scintigraphy, magnetic resonance, or ultrasound imaging. Potential research and clinical applications include studying the natural history of atherosclerosis in animal models and humans, evaluating novel drug or genetic therapies on progression and regression of atherosclerosis, evaluating plaque stability, screening and serial follow-up of high-risk individuals, non-invasive imaging of vulnerable plaques, and assessing the clinical efficacy of new treatments of atherosclerosis.

Animals↗
PubMed1994

Effects of radiolabelled murine antibody infusion on TNF-alpha, IL-1 beta, and soluble IL-2 receptor in cancer patients.

This study evaluates the plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and soluble IL-2 receptor (sIL-2R) in cancer patients infused with radiolabelled murine monoclonal antibodies (MAbs) for the purpose of imaging and dosimetry. Blood samples were collected from 13 patients (10 with colon cancer and 3 with lung cancer) before and at 4 and 7 days after infusion of either conventional intact 111In-MAb or a bifunctional antibody delivery system. For all subjects, except one, this was the first exposure to murine MAb. Before infusion, higher levels of TNF-alpha, IL-1 beta, and sIL-2R than the average expected in the plasma of healthy individuals were found. A significant decrease was noted in TNF-alpha when preinfusion concentrations were compared to 4 day (P < 0.01) or to 7 day (P < 0.05) postinfusion values. A 50% or greater decrease in IL-1 beta was also observed in most individuals with time after infusion. In contrast, sIL-2R concentrations remained relatively stable during the 1 week follow-up period. However, strikingly different patterns in the IL-1 beta and sIL-2R levels were noted in the subject who had received two previous murine antibody infusions. Our data show that the administration of radiolabelled murine antibodies, either conventional or bifunctional, can significantly alter plasma levels of TNF-alpha and IL-1 beta. These cytokines are important in immunoregulation and, perhaps also, in modulation of neoplastic growth.

Adult↗
PubMed2003

Application of 99mTc labeled chimeric Fab fragments of monoclonal antibody A7 for immunoscintigraphy of pancreatic carcinoma.

BACKGROUND: One of the reasons for the poor prognosis of pancreatic carcinoma is the difficulty of obtaining an early diagnosis of pancreatic carcinoma. One possibility is the application of radioimmunoscintigraphy using radiolabeled monoclonal antibodies (Mabs). METHODS: We labeled chimeric (human/mouse) Fab fragments of Mab A7 (chA7Fab) with (99m)Tc and examined the distribution of (99m)Tc-labeled chA7Fab in nude mice bearing human pancreatic carcinoma. RESULTS: The tumor accumulation of (99m)Tc-labeled chA7Fab was larger than that of (99m)Tc-labeled A7 from 2 to 6 hr after injection. (99m)Tc-labeled chA7Fab disappeared from blood more rapidly than (99m)Tc-labeled A7. For all resected normal tissues except kidney, the accumulation of (99m)Tc-labeled chA7Fab was low and similar to that of (99m)Tc-labeled A7. CONCLUSIONS: Because the half-life of (99m)Tc is short (6 hr), chA7Fab, which accumulates rapidly in tumors, may be a better carrier of (99m)Tc than intact Mab A7.

Animals↗
PubMed2003

Tumor markers and colorectal cancer: utility in management.

Colorectal cancer (CRC) is a leading cause of morbidity and mortality. Although genetic testing can screen for rare hereditary CRC syndromes, there is no ideal means of screening for sporadic forms of CRC. This review will focus on markers that are currently used in the management of sporadic CRC and their limitations, as well as possible future clinical applications.

Adenomatous Polyposis Coli↗