[Show abstract][Hide abstract] ABSTRACT: (1) To investigate the diagnostic value of some O-(2-[F]fluoroethyl)-L-tyrosine (F-18 FET) indices derived from the dynamic acquisition to differentiate low-grade gliomas from high-grade; (2) to analyze the course of tumor time-activity curves (TACs); and (3) to calculate the individual probability of a high-grade glioma using the logistic regression.
Seventeen low-grade (WHO I-II) and 15 high-grade (WHO III-IV) gliomas were studied with dynamic F-18 FET PET. Regions of interests were drawn over the tumor and contralateral brain, and TACs were analyzed. We considered early standardized uptake value (SUV), middle SUV, late SUV, early-to-middle SUV tumor ratio, early-to-late SUV tumor ratio; time to peak (Tpeak), in minutes, from the beginning of the dynamic acquisition up to the maximum SUV of the tumor; and SoD (sum of the frame-to-frame differences). To assess the individual probability of high-grade, logistic regression was also used.
High-grade gliomas showed significantly (P < 0.0001) higher values when compared with low-grade gliomas in early SUV, early-to-middle ratio, early-to-late ratio, Tpeak, and SoD. For the grading of gliomas, the best indices were early-to-middle ratio and Tpeak providing a diagnostic accuracy of 94%. TACs analysis provided an 87% diagnostic accuracy. For individual high-grade diagnosis, the logistic regression provided 93% sensitivity, 100% specificity, and 97% accuracy.
Early-to-middle SUV tumor ratio and Tpeak were the best indices for assessing the grading of gliomas. Since early-to-middle ratio derives from the first 35 minutes of the dynamic acquisition, the PET study could last half an hour instead of 1 hour. By logistic regression, it is possible to assess the individual probability of high-grade, useful for prognosis and treatment.
Full-text · Article · Oct 2011 · Clinical nuclear medicine
[Show abstract][Hide abstract] ABSTRACT: Innovative new software solutions may enable image fusion to produce the desired data superposition for precise target definition and follow-up studies in radiosurgery/stereotactic radiotherapy in patients with intracranial lesions. The aim is to integrate the anatomical and functional information completely into the radiation treatment planning and to achieve an exact comparison for follow-up examinations. Special conditions and advantages of BrainLAB's fully automatic image fusion system are evaluated and described for this purpose.
In 458 patients, the radiation treatment planning and some follow-up studies were performed using an automatic image fusion technique involving the use of different imaging modalities. Each fusion was visually checked and corrected as necessary. The computerized tomography (CT) scans for radiation treatment planning (slice thickness 1.25 mm), as well as stereotactic angiography for arteriovenous malformations, were acquired using head fixation with stereotactic arc or, in the case of stereotactic radiotherapy, with a relocatable stereotactic mask. Different magnetic resonance (MR) imaging sequences (T1, T2, and fluid-attenuated inversion-recovery images) and positron emission tomography (PET) scans were obtained without head fixation. Fusion results and the effects on radiation treatment planning and follow-up studies were analyzed. The precision level of the results of the automatic fusion depended primarily on the image quality, especially the slice thickness and the field homogeneity when using MR images, as well as on patient movement during data acquisition. Fully automated image fusion of different MR, CT, and PET studies was performed for each patient. Only in a few cases was it necessary to correct the fusion manually after visual evaluation. These corrections were minor and did not materially affect treatment planning. High-quality fusion of thin slices of a region of interest with a complete head data set could be performed easily. The target volume for radiation treatment planning could be accurately delineated using multimodal information provided by CT, MR, angiography, and PET studies. The fusion of follow-up image data sets yielded results that could be successfully compared and quantitatively evaluated.
Depending on the quality of the originally acquired image, automated image fusion can be a very valuable tool, allowing for fast (approximately 1-2 minute) and precise fusion of all relevant data sets. Fused multimodality imaging improves the target volume definition for radiation treatment planning. High-quality follow-up image data sets should be acquired for image fusion to provide exactly comparable slices and volumetric results that will contribute to quality contol.
Full-text · Article · Nov 2004 · Journal of Neurosurgery
[Show abstract][Hide abstract] ABSTRACT: Die radioaktive Markierung spezifischer Peptide, die gezielt an Somatostatinrezeptoren auf neuroendokrinen Tumoren binden, ermöglicht eine interne Strahlentherapie, die unter weitgehender Schonung des gesunden Gewebes (strahlenexponiert wird im Wesentlichen nur die Niere und erheblich weniger das Knochenmark) und meist nur geringer Belastung des Patienten mehrfach durchgeführt wird. Die Radiorezeptortherapie eignet sich besonders für Patienten mit langsam wachsenden hepatischen und extrahepatischen Metastasen bzw. Tumoren, die erfahrungsgemäß für eine Chemotherapie weniger geeignet und bei denen die chirurgischen Möglichkeiten der Tumorresektion erschöpft sind. Auch Patienten, die einen Progress der Erkrankung unter Octreotidtherapie bzw. kombinierter Biotherapie aufweisen, und solche mit ausgeprägter klinischer Symptomatik trotz hoch dosierter Hormontherapie kommen für eine Radiorezeptortherapie in Betracht. Die Behandlungsergebnisse der PRRT aus verschiedenen europäischen Zentren sowie von Multizenterstudien zeigen eine hohe Tumoransprechrate und einen signifikant positiven Effekt auf die klinische Symptomatik.
[Show abstract][Hide abstract] ABSTRACT: Purpose: The exact target definition even in case of very small target volumes is an important prerequisite as well for minimal invasive, stereotactic surgery as for radiosurgery (RS)/stereotactic radiotherapy (SRT) on a high accuracy level. Besides there are further contributions to the "overall process accuracy" like imaging modality, image fusion, 3D treatment planning, patient repositioning and mechanical accuracy of the used system. Based on innovative software solutions, image fusion may offer the desired data superposition within a short time. Also metabolic images from PET data sets and, in case of arteriovenous malformations, stereotactic angiographic projections (DSA) might be integrated. Special conditions and advantages of BrainLAB's fully automatic image fusion are described. Method: In the last 3.5 years 535 patients were treated with stereotactically guided biopsy/puncture or RS/SRT. For each treatment planning procedure a fully automatic image fusion of all interesting image modalities was performed. The planning CT data set (slice thickness 1.25 mm) and for arteriovenous malformations also a stereotactic DSA were acquired using head fixation with stereotactic frame or, in case of stereotactic radiotherapy, a relocatable stereotactic mask. Different sequences of MRI (slice thickness 1-2 mm) and in 17 cases F-18-FDG- or FET-PET (3.4 mm) data sets were used without head fixation. Results: The fully automatic image fusion of different MRI, CT and PET data sets could be realized in each patient. Only in few cases it visually seemed to be necessary to correct the fusion manually, with no better results. The precision of the automatic fusion result was depending on the quality of imaging modalities (especially slice thickness) and on patient movement during data acquisition. Fusing thin slices of an enlarged region of interest into another data set was also possible in a good quality. Target volume outlining could be managed in a much better way using all informations of the fused image data sets. Conclusions: Additional informations provided by PET, CT and different MRI scans enable us to improve target definition for stereotactic or neuronavigated treatment planning. The used automatic image fusion is a very accurate and reliable tool and allowes a fast (about 1-2 min) and precise fusion of all available image data sets depending on their acquisition quality.
[Show abstract][Hide abstract] ABSTRACT: A prospective analysis was performed in 124 non-small cell lung cancer patients to determine the role of F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) for molecular (metabolic) staging (n=63), therapy monitoring after induction-chemotherapy (n=34), and conformal radiation treatment planning (n=27). Staging by FDG-PET was significantly more accurate than CT (p<0.001) and changed therapeutic management in 52% of all patients. After induction-chemotherapy, patients with complete metabolic remission histologically did not show vital tumor cells in contrast to patients with metabolic partial remission or progressive disease. Metabolic radiation treatment planning by PET led to smaller planning target volumes (PTVs) for radiation therapy (between 3% and 21% in 25/27 patients), resulting in a reduction of dose exposure to healthy tissue. In two patients, PET-PTV was larger than CT-based PTV, since PET detected lymph node metastases smaller than 1 cm. FDG-PET provides clinically important information; changes therapeutic management, can predict noninvasively effectiveness of chemotherapy, and may lead to better tumor control with less radiation-induced toxicity.
Full-text · Article · Feb 2003 · Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer
[Show abstract][Hide abstract] ABSTRACT: In a case of Huntington's disease (HD) with dementia and pronounced parieto-frontal atrophy, the functional state of the affected regions was investigated using functional magnetic resonance imaging (fMRI) and fluorodeoxyglucose-positron emission tomography (FDG-PET). It was observed that although parietal areas showed extensive atrophy and reduced resting glucose metabolism, the patient performed with similar accuracy but with longer response time in a visuospatial task compared with healthy control subjects. At the same time, the blood oxygen level-dependent (BOLD) fMRI signal in these areas, which are involved in visuospatial processing, showed a similar task-dependent modulation as in control subjects. The signal amplitude (signal percent change) of the task-dependent activation was even higher for the HD patient than in the control group. This residual functionality of parietal areas involved in visuospatial processing could account for the patient's performance in the task concerned, which contrasted with his poor performance in other cognitive tasks. The increased percent-signal change suggests that a higher neuronal effort was necessary to reach a similar degree of accuracy as in control subjects, fitting well with the longer reaction time. We propose that fMRI should be considered as a tool for the assessment of functionality of morphologically abnormal cortex and for the investigation of compensatory resource allocation in neurodegenerative disorders.
No preview · Article · Mar 1999 · Psychiatry Research
[Show abstract][Hide abstract] ABSTRACT: Intravenous injection of the murine monoclonal anti-CA125 antibody B43.13 (Ovarex: Ab1) into ovarian cancer patients led to the induction of an idiotypic network. Of the 75 patients who received one to ten injections of a 2-mg dose of the antibody, 48 developed anti-(mAb B43.13) antibodies (Ab2); 18 of these patients also had elevated levels of anti-[anti-(mAb B43.13)] antibodies (Ab3; = anti-CA125 antibodies) compared to pre-injection values. Characterization of these antibodies revealed that the binding to CA125 could be inhibited by mAb B43.13 in most samples. Human anti-CA125 antibodies or Ab3 purified from patient serum samples specifically recognized human ovarian tumor cells and tissues expressing CA125. In addition, these anti-CA125 antibodies were able to conduct Fc-mediated tumor cell killing (antibody-dependent cell-mediated cytotoxicity). This raises the possibility of using an Ab1 for anti-idiotype induction immunotherapy of cancer.
No preview · Article · Jul 1998 · Cancer Immunology and Immunotherapy
[Show abstract][Hide abstract] ABSTRACT: OVAREX MAb B43.13 is a new radiopharmaceutical based on a monoclonal antibody (MAb-B43.13) known to recognize CA 125, a tumour antigen associated with epithelial ovarian cancer. This MAb is capable of facile radiolabelling with 99Tcm and has been shown previously to localize in the tumours of ovarian cancer patients. The present study was initiated to measure the pharmacokinetics of this MAb in the serum of 10 patients with primary or metastatic ovarian cancer. A two-compartment model was found to be best at representing the biodistribution of the 99Tcm-labelled MAb, yielding a 2.6 h distribution phase half-life and a 31.3 h elimination phase half-life. The serum and renal clearances for 99Tcm-MAb-B43.13 were 121 and 53 ml h-1 respectively. These parameters were compared with a similar model developed from the serum values of the MAb itself (determined using an ELISA detection method). Based on the serum pharmacokinetics of 99Tcm-MAb-B43.13 and whole-body planar gamma camera images, an estimate of the radiation dose from 99Tcm was calculated using standard MIRD schema. The organs demonstrating significant 99Tcm uptake included the liver, kidneys, heart and spleen. The whole-body dose was similar to other 99Tcm-labelled MAbs.
No preview · Article · Oct 1997 · Nuclear Medicine Communications
[Show abstract][Hide abstract] ABSTRACT: This study presents immunoscintigraphic results in 24 patients suffering from primary colorectal cancer, recurrent or metastatic disease after the injection of 1197-1351 MBq technetium-99m labelled totally human monoclonal antibody 88BV59. Labelling efficacy of 99mTc-88BV59 ranged from 97% to 99%. Immunoscintigraphy was performed 18-20 h after injection. Scintigraphic findings were compared with those of computed tomography (CT). Patients underwent surgery in order to evaluate immunoscintigraphic findings histologically. Sera of the patients (before injection and 1 and 3 months post infusion) were analysed for the presence of human anti-human antibodies (HAHA). None of the patients showed a HAHA response as assessed by a solid-phase ELISA assay. The antibody scan detected about 25% more lesions than CT. In the detection of extrahepatic disease, the sensitivity of the antibody scan proved to be 68%, whereas the sensitivity of CT was 41%.
No preview · Article · Feb 1997 · European Journal of Nuclear Medicine
[Show abstract][Hide abstract] ABSTRACT: Previous studies have shown high accuracy for immunoscintigraphy with 99mTc-MAb-174 in patients with squamous-cell carcinoma of the head and neck region compared to CT and MRI. We conducted a prospective study to determine if immunoscintigraphy provides additional diagnostic information for radiation treatment planning.
Radioimmunoscintigraphy (RIS) was performed on 40 patients (planar, whole-body, SPECT) with histologically confirmed squamous-cell carcinoma (30 primary tumors, 10 recurrences) after injection of the 99mTc (1.1 GBq) labeled monoclonal anti-squamous-cell cancer antibody 174H0.64 (murine IgG1). Results were combined with information obtained by clinical examination, sonography, panendoscopy and x-ray CT. The strategy for radiation treatment and the required treatment volumes were defined with and without immunoscintigraphical findings.
Additional diagnostically relevant information from RIS was obtained from 10 patients (25%) with advanced tumors or recurrences. In three patients (7.5%), the treatment volume had to be extended. The therapeutic strategy for seven patients (17.5%) had to be changed due to the detection of metastatic disease beyond the head and neck region. RIS of patients with squamous-cell cancers of the head and neck region with 99mTcMAb-174H0.64 enabled the detection of tumors that were not depicted by other conventional diagnostic imaging procedures.
The use of RIS in radiation treatment planning of advanced tumors of the head and neck region appears to yield important diagnostic information that may alter patient management.
Full-text · Article · Jan 1997 · Journal of Nuclear Medicine
[Show abstract][Hide abstract] ABSTRACT: The longer survival of ovarian cancer patients after immunostimulation has been connected with the induction of an anti-tumor activity triggered by cellular and humoral immune responses. Our interest was to study the long-term influence on the immune system in relation to the various levels of the HAMA response and the disease stage. The immunological profile was evaluated by regularly performing phenotyping and functional analysis of peripheral blood lymphocytes (PBL). We report the statistical analysis of immunological data obtained in a study with 77 ovarian cancer patients examined over a period of up to 28 months. The results demonstrate that these immunological data are important for monitoring cancer patients under immunotherapy whereas they provide no prognostic significance.
No preview · Article · Apr 1995 · International Journal of Oncology
[Show abstract][Hide abstract] ABSTRACT: The monoclonal antibody (MoAb) 174H.64 (Truscint SQ, Biomira Inc.) is a murine-derived MoAb reacting with an extracellular surface component of the cytoskeletal matrix ectopically expressed on squamous-cell carcinoma cell-surface membranes. A chimeric form of this MoAb has also been produced by genetically modifying the Fc portion of the MoAb by the insertion of a human Fc fragment. During this process the isotype was altered from an IgG1 (murine) to an IgG3 (chimeric). Pilot and phase I/II clinical trials of the murine and chimeric 99mTc-labelled 174H.64 MoAbs have been undertaken at selected European and North American sites. As part of this evaluation serum, urine and image data were collected at specific time intervals and used to obtain a kinetic model to describe the in vivo distribution of the MoAbs. A two-compartment model of the form: C(t) = C1 e-lambda 1t + Cz e-lambda zt was found to best describe the serum distribution of radioactivity of both the murine and chimeric MoAbs. The initial distribution half-lives were 2.9 +/- 0.7 hours and 2.7 +/- 0.2 hours, and the terminal elimination half-lives were 17.6 +/- 3.8 hours and 22.5 +/- 1.3 hours for the murine and chimeric MoAbs, respectively. No significant difference was found between the kinetic model parameters of two MoAbs at the 95% level. Assuming a similar clinical efficacy, these MoAbs could then be used interchangeably, with the chimeric MoAb offering potential advantages in reducing HAMA response.
No preview · Article · Jan 1995 · Journal of nuclear biology and medicine (Turin, Italy: 1991)
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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'.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: Human anti-mouse antibodies (HAMA) are observed frequently after immunoscintigraphy with monoclonal antibodies (MoAb) directed against CA-125.1 As the authors have shown previously,2–5 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 postulatation 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. Cancer 1994; 73:1121–5.
[Show abstract][Hide abstract] ABSTRACT: A novel murine monoclonal antibody (MAb 174H.64) was labeled with 99mTc by a direct method. MAb 174H.64 detects a cytokeratin-associated antigen which is expressed by over 90% of all squamous cell carcinomas. Panendoscopy, sonography and computerized tomography scan were performed in all cases as well as magnetic resonance imaging (in selected patients). Pre-operative immunoscintigraphy was performed in 21 patients with histologically proven primary carcinomas (18 with remaining primary tumors and 3 with lymph node recurrences). Scintigraphic images were obtained 4-6 h after injection of 1.1 GBq of the 99mTc-labeled antibody (2 mg). Late images were acquired 18 to 24 h after injection. Single-Photon-Emission-Computed Tomography (SPECT) of the head and thorax was performed in all patients. The primary tumors were immunoscintigraphically visualized in all 18 patients with remaining primary tumor. Fifteen of 18 loco-regional lymph node metastases were visualized by immunoscintigraphy (the smallest lesions had a diameter of < 1 cm), in one patient lymph node metastases were detected by immunoscan only. Two metastatically involved lymph nodes were identified by histology only (micrometastases). Distant metastases were present in 3 patients, of which two were identified by immunoscintigraphy. Immuno-SPECT according to this method was a sensitive and specific imaging modality for preoperative staging of patients with squamous cell carcinoma of the head and neck and detected lymph node metastases with higher accuracy than conventional clinical and imaging modalities.