[Resistant arterial hypertension and a prominent sternum in a 77-year-old woman]. / Therapierefraktäre arterielle Hypertonie und prominentes Sternum bei einer 77-jährigen Patientin.

The case of a 77-year-old woman who was admitted with resistant arterial hypertension is reported. In view of a history of pheochromocytoma 2 years ago, catecholamine levels were examined and found to be elevated; in addition, MIBG scintigraphy showed a positive area in the anterior mediastinum. Computer tomography showed a tumor in the sternum. Histology confirmed metastasis from the pheochromocytoma, and the corpus was removed surgically. Currently, the patient is without any evidence of relapse.

Angiography and cerebral perfusion scintigraphy in balloon test occlusion of carotid artery in head and neck tumors.

PURPOSE: Surgery of head and neck tumors and other tumors involving the carotid artery may demand complete sacrifice of the carotid as part of the necessary tumor therapy. Sacrifice of the carotid may result in permanent brain perfusion damage. This uncorrectable procedure has to be tested beforehand in order to exclude this possibility. MATERIALS AND METHODS: In order to predict this possible unstable hemodynamic brain perfusion damage, we evaluated 12 patients with head neck tumors prior to possible sacrifice of the carotid. The following tests were applied: angiography of the neck vessels, balloon test occlusion (BTO) of the carotid lasting 10 minutes combined with perfusion reserve testing using 1000 mg acetazolamide i. v. All patients received brain perfusion scintigraphy SPECT with Tc-99 m HMPAO injected during BTO. RESULTS: All patient data were evaluated for clinical neurological defects under BTO. Perfusion of the great vessels was evaluated semiquantitatively for angiography (filling delay of the ophthalmic artery) and perfusion SPECT. None of the patients suffered from neurological defects. 9 /12 patients showed mild to severe perfusion defects. 9 /12 patients showed filling delays of more than 1 second. Both tests showed a very good correlation (p = 0.005). Only 2 /12 cases were discrepant in one degree. All severe defects were congruent in both tests. CONCLUSION: None of the patients with severe defects underwent sacrifice of the carotid. Both tests resulted in increased security regarding the prediction of possible brain perfusion damage. The combination of angiography and brain scintigraphy is logistically easy and has a high value of prediction.

3-[123I]Iodo-alpha-methyl-L-tyrosine uptake in cerebral gliomas: relationship to histological grading and prognosis.

3-[123I]Iodo-alpha-methyl-L-tyrosine (IMT) is employed clinically as a tracer of amino acid transport in brain tumours using single-photon emission tomography (SPET). This study investigates the role of IMT SPET in the non-invasive histological grading and prognostic evaluation of cerebral gliomas. The files of patients investigated by IMT SPET in our clinic between 1988 and 1996 were evaluated retrospectively. Complete follow-up was available for 58 patients with cerebral gliomas investigated by IMT SPET shortly after tumour diagnosis. Seventeen patients had low-grade gliomas (WHO grade II), 14 had anaplastic gliomas (WHO grade III) and 27 had glioblastomas (WHO grade IV). Thirty-six cases were primary tumours and 22 cases, recurrences. Maximal and mean tumour-to-brain (T/B) ratios of IMT uptake at the first IMT SPET investigation were related to histological grading and survival time. Patients with low-grade gliomas showed significantly longer survival than patients with high-grade (grade III or IV) tumours. Gliomas without contrast enhancement on computed tomography or magnetic resonance imaging scans were associated with longer patient survival than tumours with contrast enhancement. The T/B ratios of IMT SPET showed no differences in relation to histological grading [WHO grade II: 1.73+/-0.59; WHO grade III: 1.74+/-0.38; WHO grade IV: 1.59+/-0.35, (mean+/-SD, T/B ratios of mean tumour uptake)]. The median survival time of patients with a high T/B ratio on IMT SPET was not significantly different from that of patients with a low T/B ratio (T/B ratio <1.6, 14.8 months; T/B ratio > or =1.6, 13.0 months). Thus, no evidence could be found for a relationship between IMT uptake in cerebral gliomas and either histological grading or survival time. Nevertheless, IMT SPET constitutes a useful method for the detection of primary and recurrent gliomas, determination of tumour extent and individual follow-up.

Positron emission tomography (PET) for staging and evaluation of response to treatment in patients with Hodgkin's disease.

Forty two examinations utilizing F-18 FDG-PET were performed in 23 patients with Hodgkin's disease to study for involved lymphoma regions and compared to conventional staging procedures. Twenty stagings were performed at diagnosis of untreated Hodgkin's disease or at first relapse, and 22 restagings during and after chemoradiotherapy. At diagnosis in 5 of 20 patients PET and other procedures revealed different extranodal manifestations and in 3 patients established different clinical staging. PET seemed to be accurate in the assessment of lymphoma involvement in nodal sites. During follow up, in 10 out of 22 investigations different results and discrepancy were recorded, mostly due to the different extent of F-18-FDG metabolism in residual masses in lymphatic tissues compared to CT, X-ray or ultrasonography. The results indicate that PET may have advantages in the assessment of remissions in nodal sites. Less conclusive results were observed with regard to extranodal involvement or inflammatory disease. In conclusion PET may be sufficient for the staging of the majority of patients with Hodgkin's disease and particularly for assessing remission status in nodal sites, but PET may have disadvantages in the evaluation of extranodal lymphoma and inflammatory disease.

Metabolic (PET) and receptor (SPET) imaging of well- and less well-differentiated tumours: comparison with the expression of the Ki-67 antigen.

[111In-DTPA-D-Phe1]-pentetreotide has been shown to localize well-differentiated and slowly growing neuroendocrine tumours, whereas increased FDG uptake is associated with malignancy. This prospective study explores the role of metabolic (PET) and receptor (SPET) imaging in well- and less well-differentiated tumours--gastroenteropancreatic (GEP) tumours, medullary thyroid carcinomas (MTC) and thymic carcinomas--in comparison with the expression of the Ki-67 antigen. Ten patients with GEP tumours, five with MTC and five with thymic carcinomas were studied. Prior to PET, somatostatin receptor scintigraphy (SRS) was performed in all patients. Sixty minutes after the intravenous administration of 18F-FDG (370 MBq), whole-body PET was performed. In addition, the resected tissues were prepared for immunocytochemistry examination (cell cycle-associated Ki-67 antigen). Preoperative SRS detected multiple primary tumours and metastatic lesions in four patients with well-differentiated carcinoids (low Ki-67 expression). Whole-body PET demonstrated normal distribution of FDG in all of these patients. In patients with recurrent MTC and rapidly increasing CEA levels, SRS showed no in vivo somatostatin receptor expression, whereas whole-body PET localized 24 locoregional lymph node metastases with increased FDG uptake. Immunocytochemistry of the resected lymph nodes demonstrated high Ki-67 expression associated with a high proliferative activity. Similar results in receptor scintigraphic and metabolic behaviour were obtained from patients with metastasizing thymic carcinomas (high Ki-67 expression). In conclusion, SRS has been shown to localize well-differentiated GEP tumours. In contrast, FDG PET is only valuable for predicting malignancy in less well-differentiated GEP tumours and malignant MTC associated with rapidly increasing CEA levels. Therefore, an additional 18F-FDG PET procedure should only be performed if SRS is negative. Furthermore, our preliminary results suggest that increased FDG metabolism reflects the invasiveness of thymic carcinomas.

Screening for colorectal neoplasms with a new immunological human faecal haemoglobin and albumin test.

In Germany, screening for colorectal cancer shows low efficiency, which is partly due to demographic changes with a rising mean age of the population, a low participation rate and an unsatisfactory sensitivity of guaiac tests for detecting faecal occult-blood. Therefore, a pilot screening study with a new immunological faecal haemoglobin and albumin test was performed in Ostringen, Germany to assess its compliance, performance characteristics and cost-effectiveness. Two thousand, seven hundred and eighty-five persons (1,498 women and 1,287 men) collected 1 ml samples from two different sites of one stool. The upper limit of normal was 10 micrograms/g stool for haemoglobin and 100 micrograms/g stool for albumin. The compliance was 82%; 224 persons (8%) had a positive test result. Of these, 184 underwent full colonoscopy. We detected 14 colorectal cancers, 10 of which were Dukes' stage A carcinomas removed by endoscopic polypectomy, 34 large adenomas and 43 small adenomas. The detection rate for colorectal neoplasms was above the rate described for other immunological haemoglobin tests and for Haemoccult tests. The specificity of the test--defined with false-positive results if a normal colon mucosa and no other reasons for upper or lower gastrointestinal bleeding were found--was 99.5%. The cost-effectiveness was assessed by comparing the diagnostic costs with the savings resulting from prevention of colorectal carcinomas by endoscopic polypectomy of malignant polyps (Dukes' stage A). The savings in our screening study exceeded the diagnostic costs by approximately 2.3 times. The combined immunological faecal haemoglobin and albumin test should substitute the Haemoccult test in colorectal cancer screening because of its higher sensitivity and specificity combined with cost-effectiveness and good patient compliance.

Comparison of metabolic and receptor imaging in recurrent medullary thyroid carcinoma with histopathological findings.

Early diagnosis of metastases of medullary thyroid carcinoma (MTC) provides the optimal condition for curative outcome. The aim of this study was to appraise the detection of metastases in patients with recurrent MTC using [111In-DTPA-d-Phe1]-pentetreotide and pentavalent technetium-99m dimercaptosuccinic acid [99mTc(V)-DMSA] in comparison with histopathological findings. Eighteen MTC patients with persistently elevated tumour marker (calcitonin, carcinoembryonic antigen) levels underwent somatostatin receptor scintigraphy using [111In-DTPA-d-Phe1]-pentetreotide (222 MBq) with early (4 h after injection) and delayed (24 h) whole-body scans and single-photon emission tomography (SPET) imaging. Metabolic whole-body and SPET imaging using 500 MBq 99mTc(V)-DMSA was performed 4 h after injection. Metabolic and receptor imaging revealed 51 sites of focal accumulation in the 18 patients investigated. Comparison with histological findings revealed that metabolic and receptor imaging had a sensitivity of 84% for the diagnosis of MTC. Using [111In-DTPA-d-Phe1]-pentetreotide, SPET discovered four lymph node metastases in two patients in whom planar views had previously identified only one lymph node metastasis, and provided no new information in the other 16 patients. In comparison, SPET studies [using 99mTc(V)-DMSA] additionally localized eight lymph node metastases in four patients and confirmed the diagnosis of hepatic metastases (n=5) in another patient in whom conventional imaging modalities and planar views had previously detected only three liver metastases. Overall, lesion detection sensitivities for 99mTc(V)-DMSA and [111In-DTPA-D-Phe1]-pentetreotide were 69% and 29%, respectively. Five surgically removed foci were adjudged false-positive with respect to MTC metastases. False-positve results were caused by lymphadenitis, an enchondroma and a pheochromocytoma (histologically proven). The smallest lesion identified by metabolic imaging was a 6 mm in diameter lymph node metastasis located in the upper mediastinum. Somatostatin receptor scintigraphy only demonstrated tumour sizes more than 1 cm in diameter. These preliminary results suggest that the combination of metabolic [99mTc(V)-DMSA] and receptor ([111In-DTPA-D-Phe1]-pentetreotide) imaging is more sensitive for tumour localization in patients with recurrent MTC than the use of only one radiopharmaceutical. However, neither 99mTc(V)-DMSA nor [111In-DTPA-D-Phe1]-pentetreotide is specific for MTC and false-positive scintigraphic findings have to be considered. Furthermore, somatostatin receptor scintigraphy cannot visualize small tumour sites (<1 cm). Further studies are needed to evaluate the role of combined metabolic and receptor imaging in the management of patients with recurrent MTC.

Validity of new immunological human fecal hemoglobin and albumin tests in detecting colorectal neoplasms--an endoscopy-controlled study.

BACKGROUND: Screening for occult blood by means of guaiac tests has an unsatisfactory sensitivity for the detection of colorectal neoplasms. To increase sensitivity and specificity the immunological determination of human hemoglobin and albumin in feces has been developed. The validity of analyzing only two samples from one bowel movement of either test is not known. METHODS: An immunological determination of human fecal hemoglobin and albumin using luminescence immunoassays (LIA) was performed in 739 patients with gastrointestinal complaints before scheduled colonoscopy. Each patient collected two 1 ml samples from one stool. There were no dietary restrictions. RESULTS: The sensitivity for detecting colorectal carcinomas was 95.3% (95% confidence interval 84.2-99.4%) with hemoglobin and 67.4% (95% confidence interval 51.2-80.9%) with albumin. The sensitivity for detecting large adenomatous polyps was 62.9% (95% confidence interval 50.5-74.1%) with hemoglobin and 32.9% (95% confidence interval 22.1-45.1%) with albumin. The specificity was 97% for hemoglobin, 96% for albumin and 94% for the combined test. CONCLUSIONS: The immunological determination of fecal hemoglobin is superior to albumin and has a better sensitivity for the detection of colorectal neoplasms than that reported for guaiac tests, even if two samples from one bowel movement are examined. The immunological determination of fecal hemoglobin should therefore be evaluated for use in colorectal cancer screening.

Intraoperative gamma probe detection of neuroendocrine tumors.

UNLABELLED: Previous studies of the intraoperative use of a handheld gamma probe to localize metastases and primary tumors of colorectal cancer have shown improved assessment of tumor spread and changes in surgical management based on added information gained by radioimmunoguided surgery. We conducted a prospective study to determine whether intraoperative radiodetection is able to reveal microscopic and occult disease of neuroendocrine tumors [medullary thyroid carcinomas (MTCs), gastroenteropancreatic (GEP) tumors]. METHODS: After the injection of 180 MBq [111In-diethylenetriaminepentaacetic acid (DTPA)-D-Phe1]pentetreotide and/or 500 MBq 99mTc-dimercaptosuccinic acid (DMSA) (both for double-nuclide scintigraphy), preoperative somatostatin receptor imaging (12 patients with GEP tumors) and double-nuclide scintigraphy (10 patients with relapsing MTCs were performed. The results were combined with the information obtained from conventional imaging modalities (CT and sonography). Intraoperative radiodetection was performed 24 hr after administration of [111In-DTPA-D-Phe1]pentetreotide or 4 hr after the injection of 99mTc-DMSA using a handheld gamma probe. RESULTS: Intraoperative gamma counting localized 70 somatostatin receptor-positive lesions of GEP tumors, whereas preoperative receptor imaging visualized 74%, surgical palpation visualized 44% and radiological imaging modalities localized only 43%. In 10 patients with recurrent MTCs, the surgeon was successful in localizing and removing 30 tumor lesions using the gamma probe. Twenty-seven of 30 lesions demonstrated tumor involvement, whereas 3 lesions were false-positive (lymphadenitis). Double-nuclide scintigraphy revealed 67% (Octreoscan, 7 of 20; 99mTc-DMSA, 13 of 20), surgical palpation revealed 60% and conventional imaging methods (CT, sonography) revealed only 50% of all lesions detected intraoperatively by the handheld gamma probe. The smallest lesion identified by the handheld probe (not palpated by the surgeon) was a lymph node metastasis (5-mm diameter). CONCLUSION: The preliminary data show that intraoperative handheld gamma probe detection of microscopic and occult endocrine tumors is feasible and more sensitive than external scintigraphy and conventional imaging.

[Combined arthroscopic and radiation synovectomy in rheumatoid arthritis]. / Synovektomie und Synoviorthese als Kombinationstherapie bei rheumatoider Arthritis.

In rheumatoid arthritis of the knee joint good results are obtained using arthroscopic synovectomy or radiation synovectomy. Aim of our study was to investigate, whether the combination of these two minimal invasive interventions achieves better results. First we performed arthroscopic synovectomy of the knee joint followed by radiation synovectomy with application of 111-222 MBq Yttrium-90 6 weeks later. In a prospective randomised clinical trial between 1987 and 1991 we performed radiation synovectomy on 22 knee joints and combined arthroscopic and radiation synovectomy on 26 knee joints. We explored the patients preoperatively, 6 weeks and 6 months postoperatively. In 1996 we evaluated 141 knee joints in a retrospective clinical trial. 90 Knee joints had been treated with the combined therapy, 39 only with radiation synovectomy and 12 only with arthroscopic synovectomy. Depending on the three different therapeutic interventions, the patients were classified into midterm (3-5 years) and long-term (6-8 years) observation groups. The trials are based on the standardized ARO-Questionnaire of the knee joint, the modified ARO Knee-Score and the radiological grading according to Larsen, Dale and Eek. In the prospective clinical trial we found significant better results for patients treated with the combined therapy than for patients treated with radiation synovectomy only regarding the parameter swelling, effusion, range of motion, pain and Knee-Score. In the long-term results of the retrospective clinical trial the patients treated with the combined therapy showed a significant better outcome for the parameters pain, swelling and Knee-Score, than the patients treated with radiation synovectomy. Although no statistically significant difference was found comparing the results of the combined therapy with arthroscopic synovectomy, an improvement of the clinical outcome can be observed performing arthroscopic synovectomy followed by radiation synovectomy. In the treatment of rheumatoid arthritis of the knee joint a better outcome is achieved performing combined arthroscopic and radiation synovectomy than performing only one of the methods.

Combined arthroscopic and radiation synovectomy in rheumatoid arthritis.

In rheumatoid arthritis of the knee joint good results are obtained using arthroscopic synovectomy or radiation synovectomy. Aim of our study was to investigate, wether the combination of these two minimal invasive interventions achieves better results. First we performed arthroscopic synovectomy of the knee joint followed by radiation synovectomy with application of 111-222 MBq Yttrium-90 6 weeks later. In a prospective randomised clinical trial between 1987 and 1991 we performed radiation synovectomy on 22 knee joints and combined arthroscopic and radiation synovectomy on 26 knee joints. We explored the patients preoperatively, 6 weeks and 6 months postoperatively. In 1996 we evaluated 141 knee joints in a retrospective clinical trial. 90 Knee joints had been treated with the combined therapy, 39 only with radiation synovectomy and 12 only with arthroscopic synovectomy. Depending on the three different therapeutic interventions, the patients were classified into mid-term (3-5 years) and long-term (6-8 years) observation groups. The trials are based on the standardized ARO-Questionnaire of the knee joint, the modified ARO Knee-Score and the radiological grading according to Larsen, Dale and Eek. In the prospective clinical trial we found significant better results for patients treated with the combined therapy than for patients treated with radiation synovectomy only regarding the parameter swelling, effusion, range of motion, pain and Knee-Score. In the long-term results of the retrospective clinical trial the patients treated with the combined therapy showed a significant better outcome for the parameters pain, swelling and Knee-Score, than the patients treated with radiation synovectomy. Although no statistically significant difference was found comparing the results of the combined therapy with arthroscopic synovectomy, an improvement of the clinical outcome can be observed performing arthroscopic synovectomy followed by radiation synovectomy. In the treatment of rheumatoid arthritis of the knee joint a better outcome is achieved performing combined arthroscopic and radiation synovectomy than performing only one of the methods.

[Lymph drainage routes and variability in preoperative efferent lymph flow scintigraphy in malignant melanoma of the trunk]. / Drainagewege und Variabilität bei der präoperativen Lymphabflussszintigraphie beim malignen Melanom des Rumpfes.

Malignant melanoma of the skin has become a real problem due to the increasing number of cases. No other tumor is induced by long term UV-radiation of the skin. Excision of the primary tumor is the treatment of choice in this disease. Before excision of the tumor lymphoscintigraphy is the first choice in diagnosis to demonstrate the draining lymph vessels and lymph node groups of an malignant melanoma for later operation. This work current the status quo of lymphoscintigraphy in malignant melanoma of the trunk.

[Systemic infection due to group A Streptococcus pyogenes]. / Systemische Infektion mit Streptococcus pyogenes der Gruppe A.

A 47-year-old woman developed oedematous swelling of the skin over the left hip and leg, with joint pains and reddening over joints of the hands and left ankle. 2 months before her son had had scarlet fever, following which the patient had two episodes of fever. Shortly before hospitalization she was treated with a glucocorticoid because a rheumatic disease had been suspected. On admission the blood sedimentation rate was 58/90, the white cell count was 15.100/microliters with left shift in the differential count. The swellings in arms and legs became abscesses which were incised. An abscess over the left buttock, diagnosed by 67-gallium whole-body scintigraphy, was also treated surgically. On the day of admission penicillin (10 mill. IU three times daily intravenously) and, from the 4th day onwards, gentamicin (80 mg three times daily intravenously) were administered. Histological examination of fascia and muscle biopsies revealed nonspecific inflammation without signs of malignancy, white blood culture grew group A Streptococcus pyogenes. 20 days after the surgical intervention the patient was discharged in full health. Necrotizing fasciitis caused by Streptococcus pyogenes has become more frequent in the last few years and has often been accompanied by severe systemic complications.

Reversal of chemoresistance in malignant gliomas by calcium antagonists: correlation with the expression of multidrug-resistant p-glycoprotein.

Resistance to multiple drugs is often observed in malignant gliomas. The authors used a microtiter tetrazolium test to analyze primary in vitro chemoresistance and chemosensitivity of 15 early cultures of human malignant glioma exposed to 50 micrograms/ml (1,4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosoure a (ACNU), 50 micrograms/ml cisplatin, 1 microgram/ml vincristine, or combinations of these chemotherapeutic agents. Primary chemoresistance was observed in 87% of tumors for ACNU, in 87% for cisplatin, and in 83% for vincristine. All tumors were examined for expression of multidrug-resistant p-glycoprotein, a transport protein of 170,000 D, by means of immunohistochemical staining with the JSB-1 antibody on paraffinized tumor sections. Eight of 15 specimens (53%) showed positive staining for the monoclonal antibody. Primary chemoresistance was overcome by addition of the calcium antagonists verapamil or nimodipine to the cultures if the original tumor expressed p-glycoprotein (p < 0.01 for verapamil, p < 0.05 for nimodipine). In tumors not expressing p-glycoprotein, addition of calcium antagonists to the cell cultures did not influence primary chemoresistance. It is concluded from these data that addition of calcium antagonists to the adjuvant chemotherapy of malignant gliomas might overcome primary chemoresistance in tumors expressing the multidrug-resistant phenotype.

[Immunoscintigraphy of carcinomas in the area of the head-neck with technetium-99m marked monoclonal antibody 174H.64. A new diagnostic procedure]. / Immunszintigraphie von Karzinomen im Kopf-Hals-Bereich mit Technetium-99m-markiertem monoklonalem Antikörper 174H.64. Ein neues diagnostisches Verfahren.

Twenty-one patients with squamous cell carcinomas of the head and neck were studied by immunoscintigraphy and immunoemission, computed tomography (ECT) using monoclonal antibody 174H.64 (Biomira Edminton) labelled with 99Tcm (Schwartz Method). Immunoscintigraphic results were compared with routine clinical assessments, including CT and ultrasonography, and were controlled by histopathological examination after surgery. All primary localizations (pT1 = 3, pT2 = 3, pT3 = 7, pT4 = 5; oropharynx 7, larynx 5, hypopharynx 3, oral cavity 3, lymph nodes 3) could be visualized, while 15 out of 18 neck lesions from tumor metastases could also be visualized (pN1 = 8, pN2 = 8, pN3 = 2). In one case with micrometastases in lymph nodes that could not be demonstrated by other methods, staging was upgraded by the immunoscintigraphic results. Three other micrometastases in lymph nodes could not be visualized. Distant metastases were suspected in 5 cases, three of which were confirmed either histologically or by radiography. Two of the cases with distant metastases were detected by the immunoscintigraphy. The present results indicate that immunoscintigraphy in combination with immuno-ECT can improve preoperative staging of head and neck carcinomas, especially with regard to metastatic neck disease, tumor recurrences and some cases of distant metastases.

A preliminary study on the functional analysis of peripheral blood lymphocytes from ovarian cancer patients developing HAMA after immunoscintigraphy.

In the follow-up of ovarian cancer patients, rising levels of the tumor-associated antigen CA 125 are an indication for immunoscintigraphy. Human anti-mouse antibodies (HAMA) are frequently found after immunoscintigraphy with murine MAb directed against CA 125. Since we observed that patients developing high HAMA-levels in serum remained free of tumor or had stable disease, we examined the cytotoxic activity of peripheral blood lymphocytes (PBL) by a fluorescence-based assay. Our results demonstrate that PBLs of patients with high anti-idiotypic antibodies show an increased cytotoxic activity (by a factor of 4) compared to those of patients with low HAMA levels. The clinical course of the patients after the first injection of murine monoclonal antibody was observed over a period of 1 to 3 years. Improvement or deterioration of patients' clinical condition corresponded with the results obtained by functional analysis. Further investigations concerning the course of cytotoxic activity in HAMA-positive patients will have to clarify HAMA's role in the immune response.

Activating anti-idiotypic human anti-mouse antibodies for immunotherapy of ovarian carcinoma.

Human anti-mouse antibodies (HAMA) are observed frequently after immunoscintigraphy with monoclonal antibodies (MoAb) directed against CA-125. As the authors have shown previously, HAMA can cause false-positive CA-125 values in routine CA-125 immunoradiometric assay (IRMA) tumor-marker assays (in one case, up to 900 days after immunoscintigraphy). In 32 patients, the authors found a HAMA frequency of 34% (11/32: 3/7 after the first administration, 6/13 after the second, and 2/2 after the third). Ten patients developed extremely high CA-125 levels after undergoing the CIS IRMA assay (up to 80,000 U/ml) in parallel to a significant HAMA increase. The use of different assays, or HAMA removal before in vitro testing, can solve this problem. After a new CA-125 assay containing antibodies that recognize different epitopes on the CA-125 antigen (Biomira Tru-Quant OV) was applied, only mildly increased assay results or normal levels were measured. Most of HAMA-positive patients demonstrated a predominantly anti-idiotypic response, determined with two different HAMA assays. Seven patients with anti-idiotypic HAMA responses after OC-125 immunoscintigraphy remained free of tumor or had stable disease (2-42 or more months), contrary to their poor prognoses that had been made based on the underlying stages of their tumors. All of these patients are currently doing well (Karnofsky Index > 70%) and show no significant tumor progression. In light of their extremely poor prognoses (5-year survival rates of 3-5% in recurrent International Federation of Gynecology and Obstetrics III/IV stages), without further chemotherapy, these courses are extremely unusual. Preliminary in vitro experiments lead to the postulation that anti-idiotypic HAMA may trigger an antitumor effect either by suppressing the growth of CA-125-expressing cancer cells directly, or by activating the patient's immune response via induction of Ab3. Similar results are observed after immunoscintigraphy with a technetium-99m-labeled anti-CA-125 monoclonal antibody (B43.13), which the authors now also use for immunotherapy of ovarian cancer patients by repeated injections, hoping that induction of anti-idiotypic HAMA will be beneficial for prolonged survival of patients with ovarian carcinoma.

Initial clinical results with technetium-99m-labeled LL2 monoclonal antibody fragment in the radioimmunodetection of B-cell lymphomas.

BACKGROUND: Various monoclonal antibodies (MoAb) labeled with Iodine-131 or Indium-111 (In-111) have been investigated for radioimmunodetection of Hodgkin's and non-Hodgkin's lymphomas. Successful radioimmunotherapy also has been reported. The purpose of this pilot study was to stage non-Hodgkin's B-cell lymphomas (NHL) using whole body scintigraphy with technetium-99m (Tc-99m)-labeled murine monoclonal antibody LL2 (EPB-2) Fab' (Immunomedics, Morris Plains, NJ). Others have shown this MoAb to have specific binding to B-cell lymphomas by flow cytometry and immunofluorescence. Initial clinical studies by others have demonstrated targeting of NHL with the Tc-99m-labeled LL2-Fab'. METHODS: One milligram of the antibody was injected intravenously after being radiolabeled with 30 mCi Tc-99m. Fifteen patients with high (n = 6), low (n = 2), and intermediate (n = 7) grade NHL were studied. No adverse effects were noted. Planar whole body imaging and single-photon emission computed tomography were performed at 2-6 h and 20-24 h postinjection. Human anti-mouse antibody levels were determined before injection and at 2 and 6 weeks. RESULTS: In 4 of 15 patients (27%), the disease stage was altered in response to the scintigraphic findings. The physiologic biodistribution of the antibody demonstrated splenic uptake caused by antibody targeting of the white pulp and of normal B-cells, and renal uptake caused by urinary excretion. Lymph node and bone marrow involvement of known tumor sites were clearly seen. A number of previously unknown tumor sites were revealed by LL2-radioimmunodetection despite normal morphologic imaging results. Long-term follow-up of these patients is required to verify these findings. No human anti-mouse antibody elevations or adverse reactions were found in the patients studied. CONCLUSION: These preliminary data suggest that Tc-99m-labeled LL2 Fab' yields useful clinical results, especially for the staging of patients with NHL before initial therapy or for the detection of early disease recurrence.