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1.
Lupus ; 27(6): 1039-1044, 2018 May.
Article in English | MEDLINE | ID: mdl-29460702

ABSTRACT

Background Systemic lupus erythematosus (SLE) is a complex autoimmune disease that occurs worldwide in both children and adults, with different disease manifestations, activity and severity between them. Objectives To analyse the difference in disease onset patterns and activity in Egyptian children and adults with SLE. Methods A retrospective cohort study conducted on 298 Egyptian SLE patients, 215 adults (a-SLE) (>18 years) and 83 children (j-SLE) (≤18 years). Disease onset, clinical manifestations and laboratory investigations were recorded. The systemic lupus erythematosus disease activity index (SLEDAI) was used to assess disease onset activity; renal biopsy was performed for all cases affected with renal symptoms. Results A total of 215 a-SLE (F/M: 14.4/1), mean age 29.65 ± 10.235 years, and 83 j-SLE (F/M: 5.4/1), mean age at diagnosis 12.63 ± 3.112 years. The most frequent initial a-SLE symptoms were constitutional (88.8%), mucocutaneous (71.2%), haematological (64.2%), articular (62.3%), renal (43.7%), vascular (15.3%), serositis (14.4%) and finally central nervous system (11.6%). There were no significant differences between a-SLE and j-SLE with regard to constitutional, mucocutaneous, renal, vascular and serositis manifestations, which were 92.8%, 74.7%, 53%, 16.9% and 10.8%, respectively, but the j-SLE haematological (88%) and central nervous system (30.1%) manifestations were significantly higher than a-SLE and articular manifestations were significantly lower in j-SLE (14.5%) than a-SLE. Antinuclear antibodies were positive for 95.3% of a-SLE and 97.6% of j-SLE. Anti-dsDNA was positive for 84.7% a-SLE and was significantly higher in j-SLE (92.8%). The SLEDAI score was 12.23 ± 4.966 in a-SLE and was significantly higher in j-SLE (27.13 ± 19.968). International Society of Nephrology lupus nephritis classes III and IV (42.4%) were the commonest findings in a-SLE; however, classes I and III (57.9%) were the commonest in j-SLE. Conclusions SLE had a wide variety of clinical and immunological manifestations, with some similarity and differences between a-SLE and j-SLE; juvenile onset lupus had a higher SLEDAI with more aggressive initial manifestations than a-SLE.


Subject(s)
Lupus Erythematosus, Systemic/epidemiology , Adolescent , Adult , Age of Onset , Autoantibodies/blood , Biomarkers/blood , Child , Egypt/epidemiology , Female , Humans , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/immunology , Male , Prognosis , Retrospective Studies , Risk Factors , Severity of Illness Index , Young Adult
2.
Lupus ; 24(13): 1455-61, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26223297

ABSTRACT

OBJECTIVE: The objective of this article is to define disease onset pattern and understand the response to therapy in children with systemic lupus erythematosus (SLE) in Egypt. METHODS: A prospective cohort of 41 Egyptian children diagnosed with SLE was analyzed. SLE Disease Activity Index (SLEDAI) score was used to record disease activity at onset, and renal biopsy was performed to define the stage of lupus nephritis. Response to therapy over a follow-up period ranging from 10 to 50 months was evaluated. RESULTS: The mean age at diagnosis was 12.12 ± 3.45 years. Thirty-six (87.8%) patients were females. Most patients had multiple manifestations at onset. The most common presenting symptoms were pallor and fever (51.2% and 43.9%, respectively). Lupus nephritis was found in 27 (65.9%) children. International Society of Nephrology (ISN) classes I and III were the most common findings on renal biopsy. Neuropsychiatric manifestations were present at disease onset in 19 patients (46.3%) with a bad prognostic course. At diagnosis, high SLEDAI scores were recorded (mean: 29.95 ± 2.06). The mean renal SLEDAI score was 10.2 ± 4. At follow-up 16 (39.02%) patients were in complete remission, 10 (24.39%) were in partial remission, two (4.87%) had active disease, five (12.9%) had relapsed, four (9.75%) had died and four (9.75%) patients were lost to follow-up. CONCLUSIONS: Egyptian children with SLE appear to have severe disease on presentation with high SLEDAI scores and high prevalence of lupus nephritis, but respond well to therapy with a favorable short-term prognosis.


Subject(s)
Lupus Erythematosus, Systemic/diagnosis , Lupus Nephritis/diagnosis , Adolescent , Age of Onset , Child , Cohort Studies , Egypt/epidemiology , Female , Follow-Up Studies , Humans , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/epidemiology , Lupus Erythematosus, Systemic/immunology , Lupus Nephritis/drug therapy , Lupus Nephritis/epidemiology , Lupus Nephritis/immunology , Male , Prospective Studies
3.
Neuroimage ; 44(2): 312-8, 2009 Jan 15.
Article in English | MEDLINE | ID: mdl-18948211

ABSTRACT

Although much is known about the perceptual characteristics of tinnitus, its neural origins remain poorly understood. We investigated the pattern of neural activation in central auditory structures using positron emission tomography (PET) imaging in a rat model of salicylate-induced tinnitus. Awake rats were injected with the metabolic tracer, fluorine-18 fluorodeoxyglucose (FDG), once in a quiet state (baseline) and once during salicylate-induced tinnitus. Tinnitus was verified using a behavioral technique. Brain imaging was performed using a high-resolution microPET scanner. Rats underwent magnetic resonance imaging (MRI) and reconstructed MRI and microPET images were fused to identify brain structures. FDG activity in brain regions of interest were quantified and compared. MicroPET imaging showed that FDG activity in the frontal pole was stable between baseline and tinnitus conditions, suggesting it was metabolically inert during tinnitus. Inferior colliculi (p=0.03) and temporal cortices (p=0.003) showed significantly increased FDG activity during tinnitus relative to baseline; activity in the colliculi and temporal cortices increased by 17%+/-21% and 29%+/-20%, respectively. FDG activity in the thalami also increased during tinnitus, but the increase did not reach statistical significance (p=0.07). Our results show increased metabolic activity consistent with neuronal activation in inferior colliculi and auditory cortices of rats during salicylate-induced tinnitus. These results are the first to show that microPET imaging can be used to identify central auditory structures involved in tinnitus and suggest that microPET imaging might be used to evaluate the therapeutic potential of drugs to treat tinnitus.


Subject(s)
Brain/diagnostic imaging , Brain/metabolism , Disease Models, Animal , Fluorodeoxyglucose F18/pharmacokinetics , Sodium Salicylate , Tinnitus/diagnostic imaging , Tinnitus/metabolism , Animals , Brain/drug effects , Humans , Male , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics , Rats , Rats, Sprague-Dawley , Tinnitus/chemically induced
4.
Dentomaxillofac Radiol ; 29(4): 216-22, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10918454

ABSTRACT

OBJECTIVE: To examine the feasibility of substituting observers determining the accuracy of endodontic measurements for measurements of physical qualities in comparison of digital imaging systems. METHODS: Sensors from six digital imaging systems were compared for signal-to-noise ratio (SNR), modulation transfer function (MTF) and detective quantum efficiency (DQE). A total of 45 canals in teeth from human cadavers were instrumented to their apical foramina. Endodontic files, ranging in size from size 8 to size 20, were glued in place at random distances from the apical foramina spanning a range of +/- 3 mm. The teeth were imaged with the six digital systems and dental X-ray film. Fifteen dentists independently measured the distance from the end of the file to the apical foramen. Results were expressed as the measurement error. Measurement error was compared to SNR, MTF and DQE for each digital system. RESULTS: CDR (Schick, New York, NY, USA), Digora (Sordex, Helsinki, Finland) and Dexis (Provision Dental Systems, Palo Alto, CA, USA) produced the highest SNR values followed closely by RVG-4 (Trophy, Croissy-Beavborg, France). Sens-A-Ray (Dent-X/Regam Medical Systems, Sundsvall, Sweden), Dexis and the RVG-4 produced the best MTF results. Dexis had the greatest DQE. The mean measurement errors (in mm) were: Film 0.65, Dexis 0.69, CDR 0.71, RVG-4 0.74, Digora 0.89, Sens-A-Ray 0.97, and Visualix-2 (Gendex, Monza, Italy) 0.98. CONCLUSIONS: Digital systems closely approximate film in their accuracy when used for endodontic measurement providing that the assessment instruments have similar resolving power. DQE was the best physical predictor of system accuracy when compared with endodontic length measurements. MTF and SNR alone did not accurately predict observer precision.


Subject(s)
Dental Pulp Cavity/anatomy & histology , Radiography, Dental, Digital , Root Canal Preparation/instrumentation , Cadaver , Dental Pulp Cavity/diagnostic imaging , Feasibility Studies , Humans , Image Processing, Computer-Assisted , Observer Variation , Radiographic Image Enhancement , Radiography, Dental, Digital/instrumentation , Reproducibility of Results , Signal Processing, Computer-Assisted , Tooth Apex/anatomy & histology , Tooth Apex/diagnostic imaging , X-Ray Film
5.
Cancer ; 89(1): 104-15, 2000 Jul 01.
Article in English | MEDLINE | ID: mdl-10897007

ABSTRACT

BACKGROUND: An adjunctive noninvasive test that is predictable and highly specific for breast carcinoma would complement the high false-positive rate of mammography in certain patients. METHODS: This prospective, multicenter study evaluated the accuracy, safety, and immunogenicity of carcinoembryonic antigen (CEA) antibody imaging in women with known or suspected breast carcinoma. Scintigraphic breast images were obtained approximately 3-8 hours after the administration of technetium 99m ((99)Tc) labeled anti-CEA Fab' and correlated with histopathology. RESULTS: The (99)Tc labeled anti-CEA Fab' detected tumor CEA expression in 46 of 49 women (94%) initially entered with known primary breast carcinoma regardless of histology or serum CEA levels. In women scheduled for biopsy confirmation of mammographic and physical examination findings, 104 (99)Tc labeled anti-CEA Fab' studies had a sensitivity of 61% (17 of 28 cases) and a specificity of 91% (69 of 76 cases). In total, (99)Tc labeled anti-CEA Fab' detected 52 of 62 invasive ductal carcinomas, 5 of 5 invasive lobular carcinomas, and 3 of 6 noninvasive tumors (2 ductal carcinomas in situ and 1 intracystic papillary carcinoma). Tumor size significantly affected sensitivity (P = 0.041), with 11 of 14 missed lesions

Subject(s)
Breast Neoplasms/diagnostic imaging , Carcinoembryonic Antigen/analysis , Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging , Mammography , Radioimmunodetection , Adult , Aged , Breast Neoplasms/immunology , Carcinoma, Ductal, Breast/diagnostic imaging , Carcinoma, Lobular/diagnostic imaging , Carcinoma, Papillary/diagnostic imaging , False Positive Reactions , Female , Humans , Immunoglobulin Fab Fragments , Mass Screening , Middle Aged , Neoplasm Invasiveness , Prospective Studies , Sensitivity and Specificity , Technetium
6.
Clin Positron Imaging ; 3(4): 163, 2000 Jul.
Article in English | MEDLINE | ID: mdl-11150766

ABSTRACT

Purpose: The purpose of this study was to assess the accuracy in localizing mediastinal, hilar and intraparenchymal lymphadenopathy in patients with primary lung carcinomas, using FDG-PET and CT of the thorax and to correlate with surgical pathology.Method: Thirty-five patients with primary lung carcinomas and minimal metastatic lymph node involvement, (either N solidus in circle or N1 disease) underwent FDG-PET and CT of the thorax prior to surgical intervention. Both FDG-PET and CT of the thorax were blindly read independent of one another.Results: Histologically, 23 patients had negative lymph nodes (N solidus in circle) and 12 patients had N1 disease. The imaging performance characteristics for FDG-PET and CT of the thorax in N solidus in circle/N1 disease was evaluated and reported in Table 1.Conclusion: This study demonstrates the higher specificity, accuracy, PPV, and NPV of FDG-PET over CT of the thorax in patients with minimal lymph node disease.

8.
Ann Surg Oncol ; 5(6): 489-94, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9754756

ABSTRACT

BACKGROUND: External immunoscintigraphy using a single monoclonal antibody has been employed successfully to localize primary, recurrent, and occult colorectal carcinoma. This prospective study investigated the accuracy and sensitivity of external immunoscintigraphy when the combination or "cocktail" of radiolabeled monoclonal antibodies, CYT-103 (an IgG1a) and CYT-372 (an IgG2b) directed against TAG-72 and CEA, respectively, is given to patients with known or suspected colorectal cancer. METHODS: Eleven patients enrolled in this open label phase I/II study underwent preoperative external immunoscintigraphy after intravenous cocktail administration of two indium 111-labeled monoclonal antibodies (MoAb), CYT103 and CYT372. Antibody dose ranged from 0.2 mg (five patients) to 1.0 mg (six patients), each antibody radiolabeled with 2.5 mCi of indium 111, delivering a total dose of 5 mCi per patient. Planar and SPECT images were performed 2 to 5 days postinjection. Suspected lesions were surgically resected within 2 weeks of injection. RESULTS: A total of 23 lesions (sites) were identified in the eleven patients, 19 of which were confirmed by pathology (hematoxylin and eosin [H&E]). Cocktail immunoscintigrams identified 16 of the 19 confirmed lesions. Computed tomography (CT) scan detected 9 of the 19 lesions. The sensitivities of cocktail immunoscintigraphy and CT scan for the detection of colorectal cancer were 84% and 64%, respectively. The positive predictive value for immunoscintigraphy was 94%. The antibody scans detected six occult, previously unsuspected lesions. Cocktail immunoscintigraphy changed the surgical management in four of the 11 (36%) patients. CONCLUSIONS: The combination of In 111 CYT-103 and CYT-372 improved the sensitivity of external immunoscintigraphy for the detection of colorectal cancer compared to that obtained with a single MoAb imaging. Cocktail antibody imaging may enhance the staging and management of patients with cancers of colon and rectum.


Subject(s)
Antibodies, Monoclonal , Colorectal Neoplasms/diagnostic imaging , Indium Radioisotopes , Radioimmunodetection , Aged , Antigens, Neoplasm , Carcinoembryonic Antigen , Colorectal Neoplasms/surgery , Female , Glycoproteins , Humans , Male , Middle Aged , Oligopeptides , Pentetic Acid/analogs & derivatives , Prospective Studies , Sensitivity and Specificity , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray Computed
9.
Radiology ; 206(3): 755-60, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9494497

ABSTRACT

PURPOSE: To evaluate the diagnostic usefulness of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) in patients with primary colorectal carcinomas. MATERIALS AND METHODS: Forty-eight patients with biopsy-proved (n = 44) or high clinical suspicion for (n = 4) colorectal cancer underwent whole-body PET after intravenous administration of 10 mCi (370 MBq) of FDG. FDG PET results were correlated with computed tomographic (CT), surgical, and histopathologic findings. RESULTS: PET depicted all known intraluminal carcinomas in 37 patients (including two in situ carcinomas) (sensitivity, 100%), but findings were false-positive in four of seven patients without cancer (three with inflammatory bowel conditions, one who had undergone polypectomy). Specificity was 43% (three of seven patients); positive predictive value, 90% (37 of 41 patients); and negative predictive value, 100% (three of three patients). No FDG accumulation was noted in 35 hyperplastic polyps. FDG PET depicted lymph node metastases in four of 14 patients (sensitivity, 29%). Results were similar to those obtained with CT (true-positive, two of seven patients [sensitivity, 29%]; true-negative, 22 of 26 patients [specificity, 85%]). FDG PET depicted liver metastases in seven of eight patients and was superior to CT, which depicted liver metastases in three patients (sensitivity of 88% and 38%, respectively). FDG PET and CT, respectively, correctly depicted the absence of liver metastases in 35 and 32 patients (specificity, 100% and 97%; negative predictive value, 97% and 86%). CONCLUSION: FDG PET has a high sensitivity and specificity for detection of colorectal carcinomas (primary and liver metastases) and appears to be superior to CT in the staging of primary colorectal carcinoma.


Subject(s)
Adenocarcinoma/diagnostic imaging , Colorectal Neoplasms/diagnostic imaging , Fluorine Radioisotopes , Fluorodeoxyglucose F18 , Tomography, Emission-Computed , Adenocarcinoma/pathology , Adenocarcinoma/secondary , Aged , Colorectal Neoplasms/pathology , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Lymphatic Metastasis , Male , Neoplasm Staging , Predictive Value of Tests , Sensitivity and Specificity , Tomography, X-Ray Computed
10.
Am Surg ; 62(11): 956-60, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8895722

ABSTRACT

Colorectal cancer has continued to increase in incidence over the past 25 years. It now ranks as the second most common noncutaneous malignancy for men and women together. The projected 1995 statistics predict 153,000 new cases in the United States, with 109,000 of colonic origin and 44,000 cancers of the rectum. The shift to more proximal colonic involvement and a decrease in size of the presenting lesion is again noted. Unfortunately, the warning signals (rectal bleeding, change in bowel habits and, later, abdominal pain, distention, and weight loss), often become evident only after the tumor has progressed significantly in the patient. Despite improvements in endoscopic detection, anesthesia, pre- and postoperative care and more extensive en-bloc resections, the cure rate for all patients with colorectal cancer remains unchanged at 53 per cent at five years. Although radical resectional surgery is relied on for locoregional control of the disease, there has been an increased use of cross-sectional radiologic studies for staging of the cancer. This newer management of colorectal cancer is the result of a better understanding of the natural history and biologic behavior of the cancer. The main strategy presently is to diagnose the disease sooner, stage the cancer more accurately, select tumors that will respond to adjuvant therapy, and detect recurrences more efficiently. It is in the area of staging of the primary tumor and accurate localization of recurrences that this new modality, immunoscintigraphy, is felt to have an impact.


Subject(s)
Colorectal Neoplasms/diagnostic imaging , Radioimmunodetection , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Female , Humans , Male , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery
11.
Semin Surg Oncol ; 12(4): 253-63, 1996.
Article in English | MEDLINE | ID: mdl-8829284

ABSTRACT

Noninvasive differentiation of benign from malignant disease has emerged as an important diagnostic challenge in this age of health-care cost containment. Most physicians today acknowledge that early and accurate detection of cancer is the key to successful treatment. Antibodies have been developed and used to detect and treat tumors. In the next few years, several radiolabeled antibodies will likely receive FDA approval for imaging colorectal, lung, and prostate carcinomas, thus expanding and improving the physician's ability to detect and follow cancer in patients. There is ample evidence in the literature that suggests that imaging with labeled antibodies is clinically useful for detecting colorectal cancer in patients with suspected recurrence, in patients with presumed isolated resectable liver metastasis, and in those at high risk of the development of recurrence. This paper reviews these studies, and also discusses some data obtained from positron emission tomography (PET) imaging in colorectal patients.


Subject(s)
Colonic Neoplasms/diagnostic imaging , Radioimmunodetection , Rectal Neoplasms/diagnostic imaging , Antibodies, Neoplasm/analysis , Carcinoma/diagnostic imaging , Colonic Neoplasms/pathology , Diagnosis, Differential , Follow-Up Studies , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Lung Neoplasms/diagnostic imaging , Male , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Staging/methods , Prostatic Neoplasms/diagnostic imaging , Radioimmunodetection/methods , Rectal Neoplasms/pathology , Risk Factors , Tomography, Emission-Computed , United States , United States Food and Drug Administration
12.
Dis Colon Rectum ; 37(2): 129-37, 1994 Feb.
Article in English | MEDLINE | ID: mdl-8306832

ABSTRACT

PURPOSE: The role of immunoscintigraphy with 111In-satumomab pendetide in the medical and/or surgical management of colorectal cancer patients was evaluated in a multicenter trial. METHODS: This 103 patient study population included 46 individuals with rising serum carcinoembryonic antigen levels and otherwise negative diagnostic evaluation, 29 patients with known recurrence, presumed to be isolated and resectable, and 28 patients for whom standard diagnostic tests provided equivocal information. RESULTS: No adverse reactions were noted following intravenous administration of 1 mg of satumomab pendetide radiolabeled with approximately 5 mCi of 111In. Thirty percent of patients developed human anti-mouse antibodies postinfusion. In the 84 patients for whom correlation with histopathologic, diagnostic, and/or clinical findings was available, antibody imaging demonstrated a sensitivity of 73 percent in patients with confirmed tumor (36/49) and negative results for all 35 patients with no evidence of malignancy. Occult disease was detected in 18 patients. CONCLUSION: 111In-satumomab pendetide immunoscintigraphy was helpful in the medical and/or surgical management of 45 (44 percent) patients and provided information unavailable from other diagnostic modalities.


Subject(s)
Adenocarcinoma/diagnostic imaging , Antibodies, Monoclonal , Colorectal Neoplasms/diagnostic imaging , Immunotoxins , Indium Radioisotopes , Oligopeptides , Pentetic Acid/analogs & derivatives , Adenocarcinoma/immunology , Adult , Animals , Carcinoembryonic Antigen/blood , Colorectal Neoplasms/immunology , Female , Humans , Male , Mice/immunology , Sensitivity and Specificity , Tomography, Emission-Computed, Single-Photon
13.
Nucl Med Commun ; 15(2): 81-93, 1994 Feb.
Article in English | MEDLINE | ID: mdl-8170642

ABSTRACT

The aims of this prospective, nonrandomized phase I/II study were to evaluate (1) the safety and (2) the detection rate of tissue culture-derived, 111In-labelled anti-CEA monoclonal antibody IVP ZCE 025 in patients with primary, metastatic and occult colorectal carcinomas. 111In-IVP ZCE 025 imaging correctly identified 31 of 37 primary colorectal carcinomas, 10 of 19 hot liver metastases, 11 of 16 distant metastases and seven of seven local tumour recurrences. Previously unsuspected tumours were detected by IVP ZCE 025 imaging in 11 of 34 patients. The scans were also true negative in four patients. The overall performance characteristics of IVP ZCE 025 at monoclonal antibody doses of 1.0-5.0 mg were comparable to those obtained with 40.0 mg ascites-produced ZCE 025. No clinical or biochemical adverse reactions were encountered in the 61 patients entered into this study.


Subject(s)
Colorectal Neoplasms/diagnostic imaging , Indium Radioisotopes , Radioimmunodetection , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/epidemiology , Female , Humans , Male , Middle Aged , Prospective Studies
14.
J Nucl Med ; 34(10): 1818-22, 1993 Oct.
Article in English | MEDLINE | ID: mdl-8410303

ABSTRACT

This study evaluated the ability of ex vivo gamma-probe scanning to detect lymph node metastases in resected surgical specimens from primary colorectal carcinoma patients undergoing external scintigraphy following intravenous administration of 4.1-5.3 mCi of 111In-labeled anti CEA monoclonal antibodies. The ex vivo probe counting technique led to a twofold to fourfold increase in the number of detectable lymph nodes with the majority measuring 2-5 mm in diameter. Results indicate a potentially useful role for ex vivo probe counting in detection and mapping small (2-5 mm) lymph nodes metastases.


Subject(s)
Colorectal Neoplasms/pathology , Indium Radioisotopes , Lymphatic Metastasis/diagnostic imaging , Radioimmunodetection , Aged , Gamma Cameras , Humans , In Vitro Techniques , Male , Methods , Middle Aged , Prospective Studies
15.
Cancer ; 71(12 Suppl): 4241-7, 1993 Jun 15.
Article in English | MEDLINE | ID: mdl-8508386

ABSTRACT

Recurrent colorectal cancer is seen in as many as 40% of patients after curative resection. In view of the limitations of endoscopic and cross-sectional imaging, external immunoscintigraphy has been added to the follow-up regimen of patients at high-risk of recurrent disease. The authors investigated the utility of immunoscintigraphy with Indium-111 (In-111) CYT-103 (site specifically labeled conjugate of monoclonal antibody B72.3) in 19 patients with suspected recurrences after previous curative resection of colorectal carcinoma. Local or regional recurrences (4 patients) and liver metastasis (6 patients) were indicated by physical examination and computed tomography (CT), whereas nine patients had occult disease with increasing serum carcinoembryonic antigen (CEA) levels and negative conventional workups. Serum CEA levels were elevated (mean, 22 ng/ml) in all patients. Approximately 4.3 mCi In-111 labeled to 1.0 mg CYT-103 was administered intravenously to each patient. Planar and single photon emission computed tomography (SPECT) imaging were performed 2-5 days after infusion. The final diagnosis of recurrence or metastasis was established in 18 patients by second-look surgery or biopsy. One patient died before exploration. Tumor was identified at the following locations: pelvis (12 patients), abdominal wall (2 patients), retroperitoneum (1 patient), liver (5 patients), and omentum (2 patients). Superiority of monoclonal antibody (MoAb) scan is noted in the detection of pelvic and intraabdominal recurrences (100%) versus CT scan (43%). Liver metastases were identified with equal facility by both modalities. In-111 CYT-103 scan findings influenced the management of 10 (55%) of 18 patients. Surgery was avoided in one patient with disseminated metastases detected by the scan. Correct identification of occult local recurrences was made in six patients. An isolated liver metastasis was confirmed in one patient with equivocal CT scan. Finally, additional intraabdominal lesions were detected in two patients. These results suggest an important and beneficial role for In-111 CYT-103 MoAb imaging in patients with suspected recurrent colorectal carcinomas, particularly in patients in whom cross-sectional imaging is negative; such imaging may prevent patients from undergoing unnecessary surgical exploration.


Subject(s)
Adenocarcinoma/diagnostic imaging , Antibodies, Monoclonal , Colonic Neoplasms/diagnostic imaging , Indium Radioisotopes , Neoplasm Recurrence, Local/diagnostic imaging , Oligopeptides , Pentetic Acid/analogs & derivatives , Radioimmunodetection , Rectal Neoplasms/diagnostic imaging , Adenocarcinoma/blood , Adenocarcinoma/secondary , Adult , Aged , Carcinoembryonic Antigen/blood , Colonic Neoplasms/blood , Female , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/secondary , Male , Middle Aged , Pelvic Neoplasms/diagnostic imaging , Pelvic Neoplasms/secondary , Rectal Neoplasms/blood
16.
Semin Nucl Med ; 23(2): 165-79, 1993 Apr.
Article in English | MEDLINE | ID: mdl-8511602

ABSTRACT

The use of radiolabeled murine monoclonal antibodies (MoAbs) for cancer immunodetection has been limited by the development of human antimouse antibodies (HAMA). Human monoclonal antibodies do not elicit a significant human antihuman (HAHA) response. The generation and production of human monoclonal antibodies met with technical difficulties that resulted in delaying their clinical testing. Human monoclonal antibodies of all isotypes have been obtained. Most were immunoglobulin (Ig) M directed against intracellular antigens. Two antibodies, 16.88 (IgM) and 88BV59 (IgG3k), recognize different epitopes on a tumor-associated antigen, CTA 16.88, homologous to cytokeratins 8, 18, and 19. CTA 16.88 is expressed by most epithelial-derived tumors including carcinomas of the colon, pancreas, breast, ovary, and lung. The in vivo targeting by these antibodies is related to their localization in nonnecrotic areas of tumors. Repeated administration of 16.88 over 5 weeks to a cumulative dose of 1,000 mg did not elicit a HAHA response. Two of 53 patients developed a low titer of HAHA 1 to 3 months after a single administration of 88BV59. Planar imaging of colorectal cancer with Iodine-131 (131I)-16.88 was positive in two studies in 9 of 12 and 16 of 20 patients preselected by immunohistochemistry. Tumors less than 2 cm in diameter are usually not detected. The lack of immunogenicity and long tumor residence time (average = 17 days) makes 16.88 a good candidate for therapy. Radioimmunlymphoscintigraphy with indium-111 (111In)-LiLo-16.88 administered by an intramammary route was used in the presurgical staging of primary breast cancer. The negative predictive value of lymph node metastases for tumors less than 3 cm was 90.5%. Planar and single photon emission computed tomography imaging of colorectal carcinoma with technetium-99m (99mTc) 88BV59 was compared with computed tomography (CT) scan in 36 surgical patients. The antibody scan was more sensitive than the CT scan in detecting abdominal and pelvic tumors: 68% versus 40% (P < .05). The combination of antibody scan and CT scan was superior to CT scan alone: 80% versus 40% (P < .01). Lesions as small as 0.5 cm in diameter were detected by antibody scan. The CT scan appears superior to the antibody scan for liver metastases. Patients with a high serum titer of HAMA from previous exposure to murine antibodies were successfully imaged. Antibody scans obtained with 99mTc-88BV59 have imaging characteristics similar to murine antibody scans obtained with radiolabeled IgGs. The absence or weak immunogenicity of the human monoclonal antibodies makes them good candidates for radioimmunodetection and radioimmunotherapy.


Subject(s)
Breast Neoplasms/diagnostic imaging , Colorectal Neoplasms/diagnostic imaging , Neoplasms/diagnostic imaging , Radioimmunodetection , Female , Humans , Iodine Radioisotopes , Technetium
17.
Semin Nucl Med ; 23(2): 99-113, 1993 Apr.
Article in English | MEDLINE | ID: mdl-8511606

ABSTRACT

During the past two decades, the in vivo application of monoclonal antibodies (MoAbs) in cancer diagnosis and therapy have been widely studied. This can be related to three main factors: (1) dramatic improvement in monoclonal antibody production, revolutionized by Kohler and Milstein; (2) improvement in radioisotopes and monoclonal antibody conjugation procedure and further simplification and ease of use of these procedures; and (3) the apparent safety of single or, in selected cases, multiple administration of MoAbs to humans. The development of radioimmunoscintigraphy or radioimmunodetection has added a significant new dimension to nuclear imaging, and it is very likely to broaden our approach to diagnosis and perhaps therapy of malignant diseases. The indications and limitation of radioimmunoscintigraphy must be clearly outlined to the referring oncologists and surgeons. The unique capability of radiolabeled MoAbs in detecting occult disease, upstaging patients, and, most importantly, changing patient management must be emphasized.


Subject(s)
Colorectal Neoplasms/diagnostic imaging , Indium Radioisotopes , Radioimmunodetection , Adult , Aged , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/secondary , Male , Tomography, Emission-Computed, Single-Photon
18.
Int J Biol Markers ; 8(2): 73-6, 1993.
Article in English | MEDLINE | ID: mdl-8366298

ABSTRACT

External immunoscintigraphy (IS) is a new imaging tool to diagnose, stage and follow-up solid malignancies. Monoclonal antibodies are raised to tumor-associated antigens, radiolabeled and when injected in the patient localize to the tumor. Detection is with nuclear medicine gamma camera. In colorectal cancer, immunoscintigraphy can be beneficial to the surgeon. With primary colorectal carcinoma, IS detects synchronous primaries, identifies lymph node metastasis, determines extent of disease and detects occult metastasis. Postoperatively, in high-risk patients (Dukes B2, B3 and C lesions) IS assists in the follow-up for recurrence. Particular advantage with IS is seen in pelvic, mesenteric and retroperitoneal recurrences. Rising serum CEA and negative conventional cross-sectional imaging can often be clarified as to site of disease with IS. IS contributes significantly to surgical decision making with alterations in management based on radiolabeled monoclonal antibody scans in 25-32% of primary and recurrent colorectal cancer cases.


Subject(s)
Colorectal Neoplasms/diagnostic imaging , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/immunology , Antigens, Neoplasm , Biomarkers, Tumor/immunology , Colorectal Neoplasms/immunology , Humans , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/immunology , Neoplasm Staging , Radioimmunodetection
19.
Radiology ; 185(1): 179-86, 1992 Oct.
Article in English | MEDLINE | ID: mdl-1523304

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal , Colorectal Neoplasms/diagnostic imaging , Indium Radioisotopes , Oligopeptides , Pentetic Acid/analogs & derivatives , Radioimmunodetection , Tomography, X-Ray Computed , Adult , Aged , Antigens, Neoplasm/blood , Colorectal Neoplasms/blood , Female , Glycoproteins/blood , Humans , Male , Middle Aged
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