ABSTRACT
PURPOSE: Aim of the study was to evaluate the impact of parenchymal blood volume (PBV) C-arm CT in transarterial radioembolization (TARE) planning procedure regarding the appropriateness of segmental blood supply from selective catheter positions defined by angiographic images compared to PBV mapsto determine the influence of changed target volumes on dose calculation. MATERIAL AND METHODS: A total of 22 consecutive patients (median age, 62 years) underwent a TARE planning procedure were included in this retrospective study. Selective angiograms and selective PBV C-arm CT (right and left liver lobe) were evaluated in a blinded fashion, regarding segmental hepatic artery variants. Volumetry of target volume and dosimetry of glass and resin microspheres were performed. RESULTS: Classification of segment IV and segment I to the corresponding target vascular bed supply was correct in 91.0% (20/22) and 86.4% (19/22) for angiography and C-arm CT, respectively. Except one case, all other liver segments were classified properly to the left and right hepatic arterial supply. Based on the mismatch of the angiographic and the C-arm CT approach, changes of target volume were evident in 27.3% of patients, resulting in a mean mismatch volume of 90±54ml (range, 51-198ml) and a percentage of dose differences of 14.2±11.8% and 12.6±10.6% for the right and 12.5±8.5% and 11.1±7.8% for the left liver lobe in glass and resin microspheres, respectively. CONCLUSION: The C-arm CT approach is superior to the angiographic determination of vascular supply of specific liver segments for dosimetry before radioembolization. Especially for unexperienced interventional radiologists or for a complex anatomy, C-arm CT improves individualized dosimetry concepts.
Subject(s)
Blood Volume/radiation effects , Embolization, Therapeutic/methods , Hepatic Artery/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/physiopathology , Tomography, X-Ray Computed/methods , Aged , Blood Volume/physiology , Female , Hepatic Artery/physiopathology , Humans , Liver/blood supply , Liver/diagnostic imaging , Liver/physiopathology , Liver Neoplasms/blood supply , Male , Microspheres , Middle Aged , Radiotherapy Dosage , Retrospective StudiesABSTRACT
SETTING: Hypothyroidism is an adverse effect of certain anti-tuberculosis drugs. DESIGN: This is a prospective study of the frequency and possible pathomechanisms associated with hypothyroidism due to second-line treatment of multidrug-resistant tuberculosis. Fifty human immunodeficiency virus negative patients and 20 controls were included. All participants underwent ultrasonography of the thyroid and measurement of thyroid stimulating hormone (TSH). TSH levels were checked every 3 months. If hypothyroidism was present, T3, T4 and thyroid peroxidase autoantibodies were measured, and imaging extended to scintigraphy and repeated ultrasonography. RESULTS: Before treatment, 7 patients (14%) and 1 control (5%) were hypothyreotic. During the first 6 months of treatment, TSH levels increased in 41 patients (82%), 39 (78%) had values above the normal range and 19 (38%) had overt hypothyroidism. As none of the patients had signs of autoimmune thyroiditis, interaction with anti-tuberculosis drugs was assumed to be the cause of hypothyroidism. Nine patients died during treatment, all of whom had developed hypothyroidism. In seven, the metabolic situation at their death was known, and they had become euthyreotic following levothyroxine substitution. CONCLUSION: TSH levels should be checked before initiating anti-tuberculosis treatment and after 3 and 6 months to start timely replacement of levothyroxine. Further studies are needed to elucidate the exact pathomechanism involved in hypothyroidism and whether hypothyroidism can be used as predictor of treatment failure.
Subject(s)
Antitubercular Agents/adverse effects , Hypothyroidism/chemically induced , Mycobacterium tuberculosis/drug effects , Tuberculosis, Multidrug-Resistant/drug therapy , Adolescent , Adult , Autoantibodies/blood , Autoantigens/immunology , Biomarkers/blood , Case-Control Studies , Female , Humans , Hypothyroidism/blood , Hypothyroidism/diagnostic imaging , Iodide Peroxidase/immunology , Iron-Binding Proteins/immunology , Male , Middle Aged , Prospective Studies , Risk Factors , Thyrotropin/blood , Thyroxine/blood , Treatment Outcome , Triiodothyronine/blood , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/microbiology , Ultrasonography , Young AdultABSTRACT
AIM: To investigate the efficacy of PET/CT with 11C-methionine for localizing parathyroid adenomas in patients with suspected primary hyperparathyroidism and inconclusive results of cervical ultrasonography and 99mTc-MIBI-SPECT/CT. PATIENTS, METHOD: Retrospective analysis of imaging data of 18 patients and correlation with clinical outcome, in particular intraoperative findings and histopathology of excised tissue. RESULTS: 12 of 18 patients received surgery. In 10 patients single parathyroid adenomas were found (diameter: 5-20 mm), 2 patients presented parathyroid hyperplasia (5 excised hyperplastic glands (diameter: 2-12 mm). PET/CT correctly localized all adenomas and 1 of 5 hyperplastic glands. The sensitivity per patient was 91.7% (11 of 12), the sensitivity per lesion 73.3% (11 of 15). All lesions missed by PET/CT had a size smaller than 9 mm and a volume of less than 0.2 ml. In 6 patients no surgery was performed. Five of them had a negative or atypical PET/CT. Further follow-up indicated familial hypocalciuric hypercalcemia in 3 of them (thus, PET/CT true negative), in the remaining 2 patients no validation is available. One patient with 2 highly suggestive lesions rejected surgery so far. CONCLUSION: PET/CT with 11C-methionine is a very sensitive method for the detection of parathyroid adenomas, even if they are too small to be visualized by 99mTc-MIBI-SPECT/CT.
Subject(s)
Adenoma/diagnosis , Hyperparathyroidism, Primary/diagnosis , Methionine , Multimodal Imaging/methods , Parathyroid Neoplasms/diagnosis , Technetium Tc 99m Sestamibi , Adenoma/etiology , Adult , Aged , Female , Humans , Hyperparathyroidism, Primary/etiology , Male , Middle Aged , Parathyroid Neoplasms/etiology , Positron-Emission Tomography/methods , Radiopharmaceuticals , Reproducibility of Results , Sensitivity and Specificity , Tomography, Emission-Computed, Single-Photon/methods , Tomography, X-Ray Computed/methodsABSTRACT
PURPOSE: PET with (68)Ga-DOTATOC allows for imaging and quantitative assessment of somatostatin receptor expression in neuroendocrine tumors (NET). The aim of this retrospective study was to analyze whether pre-therapeutic (68)Ga-DOTATOC PET/CT is able to predict response to Peptide Receptor Radionuclide Therapy (PRRT). PATIENTS AND METHODS: Forty patients with advanced stage NET were treated with a fixed dose of (90)Y-DOTATOC (5550 or 3700MBq). Prior to PRRT, each patient received (68)Ga-DOTATOC PET/CT. Treatment results were evaluated after 3months by CT, tumor marker levels and clinical course and correlated with (68)Ga-DOTATOC uptake (SUVmax) and the assumed uptake of (90)Y-DOTATOC in tumor manifestations (MBq/g). ROC analysis and pairwise comparison of area under the curve (AUC) were performed with pre-treatment uptake of (68)Ga-DOTATOC, assumed uptake of (90)Y-DOTATOC and treatment activity alone and in relation to body weight as continuous variables, and response/no response as classification variable. RESULTS: According to conventional criteria (tumor shrinkage, decrease of tumor markers, improved or stable clinical condition), 20 patients were classified as responders, 16 as non-responders and in four patients findings were equivocal. Using a SUV more than 17.9 as cut-off for favorable outcome, PET was able to predict treatment response of all responders and 15 out of 16 non-responders. All four patients with equivocal findings showed SUV less than or equal to 17.9 and soon experienced tumor progression. The assumed uptake of (90)Y-DOTATOC in tumor manifestations using a cut-off more than 1.26MBq/g as predictor of response was able to correctly classify 19 out of 20 responders, and 14 out of 16 non-responders. In all patients with equivocal findings, the assumed uptake of (90)Y-DOTATOC was below 1.26MBq/g. CONCLUSION: Pre-therapeutic (68)Ga-DOTATOC tumor uptake as well as assumed uptake of (90)Y-DOTATOC are strongly associated with the results of subsequent PRRT. The defined cut-off values should be confirmed by prospective studies and may then provide the rationale for individual dosing and selecting patients with high likelihood of favorable treatment outcome.
Subject(s)
Endovascular Procedures/methods , Neuroendocrine Tumors/radiotherapy , Organometallic Compounds , Positron-Emission Tomography/methods , Receptors, Somatostatin/analysis , Tomography, X-Ray Computed/methods , Adult , Aged , Cooperative Behavior , Female , Follow-Up Studies , Humans , Interdisciplinary Communication , Male , Middle Aged , Neoplasm Staging , Neuroendocrine Tumors/diagnostic imaging , Neuroendocrine Tumors/pathology , Predictive Value of Tests , Retrospective Studies , Treatment OutcomeABSTRACT
A total of 20 patients enrolled in a multicenter phase II dose escalation study of radioimmunotherapy (RIT) using yttrium-90-ibritumomab tiuxetan at two dose levels (22 and 30 MBq/kg) in 10 patients, combined with reduced intensity conditioning (RIC) using fludarabine, melphalan and alemtuzumab followed by allogeneic hematopoietic cell transplantation (HCT) from either matched-related (n=5) or matched-unrelated donors (n=15). Postgrafting immunosuppression with cyclosporine was administered. Diagnoses were diffuse large B-cell lymphoma (n=13), transformed CLL (n=4), blastic mantle cell lymphoma (n=2) and follicular lymphoma grade 3 (n=1). Median age was 51 (range, 29-69) years. All patients were high risk with relapsed/refractory disease or relapse after preceding autologous HCT. Median follow-up of patients alive was 1115 (range, 1006-1252) days. No directly RIT-related toxicities were observed. The cumulative incidence of non-relapse mortality was 30%. Incidences of grade II-IV acute and chronic GvHD was 45% and 70%, respectively. Kaplan-Meier estimated 3-year OS and EFS were 20% for both dose levels. In conclusion, dose escalation of RIT and combined use with RIC is feasible with no additional toxicity due to dose escalation. This study is registered on http://clinicaltrials.gov as NCT00302757.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Transplantation/methods , Lymphoma, Non-Hodgkin/radiotherapy , Radioimmunotherapy/methods , Transplantation Conditioning/methods , Yttrium Radioisotopes/therapeutic use , Adult , Aged , Alemtuzumab , Antibodies, Monoclonal, Humanized/administration & dosage , Cyclosporine/therapeutic use , Dose-Response Relationship, Radiation , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Non-Hodgkin/surgery , Male , Melphalan/administration & dosage , Middle Aged , Neoplasm Grading , Prognosis , Prospective Studies , Radioimmunotherapy/adverse effects , Radiopharmaceuticals/therapeutic use , Transplantation Conditioning/adverse effects , Transplantation, Homologous , Vidarabine/administration & dosage , Vidarabine/analogs & derivativesABSTRACT
HISTORY AND ADMISSION FINDINGS: A 27-year-old male patient with a past medical history of HIV presented with acute myeloid leukemia for allogeneic hematopoietic stem cell transplantation (HSCT). Highly active anti-retroviral therapy suppressed the viral load below detection threshold. INVESTIGATIONS: There were no contraindications for allogeneic HSCT. TREATMENT AND COURSE: Myeloablative conditioning consisted of total body irradiation and cyclophosphamide. Anti-thymocyte globulin, tacrolimus and mycophenolate mofetil were used for immunosuppression. Combined anti-retroviral therapy (nucleoside and nucleotide analog reverse-transcriptase inhibitor, boostered protease inhibitor, maraviroc and raltegravir) was maintained for allogeneic HSCT and viral load remained below detection threshold. No graft-versus-host disease or serious infectious complications occurred. The patient showed good graft function with stable hematopoiesis. Localized Kaposi's sarcoma was diagnosed six months after allogeneic HSCT and treated successfully with surgical excision and reduction of immunosuppression. Almost one year after allogeneic HSCT, the CD4+ cell count is rising and viral load remains below detection threshold with combined anti-retroviral therapy. CONCLUSION: Allogeneic HSCT can be safely performed in HIV positive patients. Kaposi's sarcoma is a rare event after allogeneic HSCT and linked to strong immunosuppression.
Subject(s)
Antiretroviral Therapy, Highly Active , HIV Infections/therapy , Leukemia, Myeloid, Acute/therapy , Stem Cell Transplantation , Adult , Combined Modality Therapy , HIV Infections/complications , HIV Infections/diagnosis , Humans , Leukemia, Myeloid, Acute/diagnosis , Male , Treatment OutcomeABSTRACT
HISTORY AND ADMISSION FINDINGS: A 51-year-old woman was admitted from a mental institution for evaluation of hypercalcemia. She was treated with lithium for a bipolar disorder since 25 years. She complained of polydypsia and polyuria. The physical examination findings were unremarkable up to manic symptoms. INVESTIGATIONS: Laboratory values showed elevated serum calcium and parathormone. Serum phosporus was within the normal range. Neck ultrasound revealed a goiter with one nodule in the right thyroid lobe and a suspected enlarged lower left parathyroid gland. The sesta-MIBI-scan failed to detect an adenoma. DIAGNOSIS, TREATMENT AND COURSE: In light of long-term treatment with lithium and negative MIBI-scan, lithium-associated- hyperparathyreoidism (LAH) was suspected. The patient refused further preoperative imaging studies, such as c-11 methionine positron emission tomography and thyroid scan. Until surgery after stabilization of the psychiatric condition, treatment with the calcimimetic cinacalcet was initiated. CONCLUSIONS: Long-term lithium therapy is frequently associated with LAH. The criteria of diagnosis and therapy are similar to those of primary hyperparathyroidism. Lithium alters the set-point of the calcium-sensing-receptor and results in elevation of parathormone und hyperplasia of the parathyroid glands. Patient with LAH have a higher prevalence of multiglandular disease compared with sporadic hyperparathyreoidism. Thus, the preoperative localization is challenging. After surgery recurrent or resistant disease is more frequent. The calcimimetic cinacalcet is a potential alternative for patients who have contraindications to surgery, refuse surgery, or experience recurrent disease after surgery.
Subject(s)
Antimanic Agents/adverse effects , Bipolar Disorder/drug therapy , Hyperparathyroidism, Primary/chemically induced , Hyperparathyroidism, Primary/diagnosis , Lithium Carbonate/adverse effects , Antimanic Agents/therapeutic use , Bipolar Disorder/blood , Diagnosis, Differential , Female , Humans , Hypercalcemia/blood , Hypercalcemia/chemically induced , Hypercalcemia/diagnosis , Hyperparathyroidism, Primary/blood , Lithium Carbonate/therapeutic use , Long-Term Care , Middle Aged , Parathyroid Hormone/bloodSubject(s)
Adrenal Gland Neoplasms/diagnosis , Pheochromocytoma/diagnosis , Adrenal Gland Neoplasms/diagnostic imaging , Humans , Magnetic Resonance Imaging , Neoplasm Metastasis/diagnostic imaging , Pheochromocytoma/diagnostic imaging , Positron-Emission Tomography , Tomography, X-Ray Computed , UltrasonographyABSTRACT
BACKGROUND: Evaluation of potential kidney donors requires the assessment of both kidney anatomy and function. In this prospective study, we sought to expand the diagnostic yield of magnetic resonance (MR) by adding functional measurements of glomerular filtration rate (GFR) and split renal function. METHODS: Between 2007 and 2009, all potential kidney donors presenting to our facility underwent a comprehensive single-stop MR study that included an assessment of anatomy, angiography and functional measurements. GFR was measured after a bolus injection of gadobutrol (4 ml, approximately 0.05 mmol/kg) and calculated from the washout of the signal intensity obtained over the liver. Split renal function was calculated from the increase of signal intensity over the renal cortex. Values were compared to renal scintigraphy with (99m)Tc-DTPA from the same day. RESULTS: The MR investigation was successfully performed in 21 participants. The GFR derived from MR (MR-GFR) correlated well (r = 0.84) with the GFR derived from scintigraphy (DTPA-GFR). The mean value of the paired differences was 4 +/- 13 [SD] ml/min/1.73 m(2) and was not significantly different from zero. The ratio between right and left kidney function was similar with both techniques (1.01 +/- 0.17 with MR and 1.06 +/- 0.12 with scintigraphy, P = 0.20). CONCLUSIONS: We demonstrate an MR-based approach to comprehensively evaluate both kidney anatomy and function in a single investigation, thereby facilitating the evaluation of potential kidney donors.
Subject(s)
Kidney Function Tests/methods , Kidney Transplantation , Kidney/anatomy & histology , Kidney/physiology , Living Donors , Magnetic Resonance Imaging/methods , Adult , Creatinine/metabolism , Female , Glomerular Filtration Rate , Humans , Kidney/blood supply , Kidney/diagnostic imaging , Kidney Function Tests/statistics & numerical data , Magnetic Resonance Angiography , Male , Middle Aged , Patient Selection , Radionuclide Imaging , Radiopharmaceuticals , Technetium Tc 99m PentetateABSTRACT
PURPOSE: The relevance of (18)F-FDG PET for staging non-small cell lung cancer (NSCLC), in particular for the detection of lymph node or distant metastases, has been shown in several studies. The value of FDG-PET for therapy monitoring in NSCLC, in contrast, has not yet been sufficiently analysed. Aim of this study was to evaluate FDG-PET for monitoring treatment response during and after neoadjuvant radiochemotherapy (NARCT) in advanced NSCLC. METHODS: Sixty-five patients with histologically proven NSCLC stage III initially underwent three FDG-PET investigations, during NARCT prior to initiating radiation, and post-NARCT. Changes of FDG-uptake in the primary tumour at two time-points during NARCT were analysed concerning their impact on long-term survival. RESULTS: The mean maximum FDG uptake (standardized uptake value, SUVmax) of the whole group decreased significantly during NARCT (SUVmax PET 1: 14.9+/-4.0, SUVmax PET 3: 5.5+/-2.4, p=0.004). The difference between initial FDG uptake (PET 1) and uptake after induction chemotherapy (PET 2) was found to be highly predictive for long-term survival patients which had a greater than 60% decreases in their SUV change had a significantly longer survival than those below this threshold (5-year-survival 60% versus 15%, p=0.0007). Patients who had a lower than 25% decrease in their SUV change had a 5-years-survival lower than 5%. Furthermore, the difference between initial FDG uptake (PET 1) and uptake after completion of the whole NARCT (PET 3) was predictive for survival when 75% was applied as cut-off (p=0.02). However, the level of significance was considerably lower. CONCLUSION: FDG-PET is suitable for therapy monitoring in patients with stage III NSCLC. The decrease of FDG uptake during induction chemotherapy is highly predictive for patient outcome.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/drug therapy , Fluorodeoxyglucose F18/pharmacokinetics , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/drug therapy , Radiopharmaceuticals/pharmacokinetics , Adult , Aged , Area Under Curve , Carboplatin/therapeutic use , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Paclitaxel/therapeutic use , Radionuclide Imaging , Survival AnalysisABSTRACT
AIM: The factors influencing success of treating Graves' disease with radioiodine ( (131)I) are discussed controversially. This study analyses prospectively the influence of discontinuing antithyroid drugs (ATD) immediately prior to treatment with radioiodine on the therapeutic outcome. METHODS: We studied 141 patients with Graves' disease. In 73 of them (group A) treatment was performed under medication with ATD, in 68 patients (group B) ATD were discontinued for 3 - 7 days starting at the time of therapy. We performed a statistical analysis of the influence of ATD and other factors potentially influencing treatment results. RESULTS: In group A 49/73 patients were treated successfully (67 %) vs. 58/68 (85 %) in group B (p < 0.01). Characteristic changes in the kinetics of radioiodine were observed: after discontinuing ATD specific uptake was higher (2.0 %/ml in group A vs. 2.6 %/ml in group B, p = 0.004), and the effective half life was longer (5.1 +/- 1.3 d in group A vs. 5.5 +/- 1.1 d in group B, p = 0.076) resulting in a significantly higher radiation dose in group B (200 +/- 61 Gy in group A vs. 236 +/- 72 Gy in group B, p = 0.002). CONCLUSION: We conclude that short-term interruption of ATD improves the success rate of treating Graves' disease with radioiodine significantly.
Subject(s)
Antithyroid Agents/therapeutic use , Graves Disease/drug therapy , Graves Disease/radiotherapy , Iodine Radioisotopes/therapeutic use , Withholding Treatment , Aged , Female , Humans , Iodine Radioisotopes/pharmacokinetics , Male , Middle Aged , Time Factors , Treatment OutcomeABSTRACT
Endocrinology and diabetology are disciplines with an interdisciplinary approach. Patients with diabetes or endocrine disorders are diagnosed and treated by multiple disciplines both in an outpatient or in-hospital setting. Additional diabetes-specific professions also participate in the care of diabetic patients. The development of clinical pathways and case-management in institutionalized "Diabetes Centers" and "Endocrinology Centers" as platforms of cooperation is one way to improve patient care and to pool resources. In such centers an interdisciplinary decision support within the diagnostic and therapeutic process is important. E. g., interdisciplinary case conferences expediate and intensify the necessary flow of information. This guarantees the implementation of a rational and concerted treatment according to guidelines and finally optimize the clinical pathways in a continuous process improvement.
Subject(s)
Critical Pathways/organization & administration , Delivery of Health Care, Integrated/organization & administration , Diabetes Mellitus/diagnosis , Diabetes Mellitus/therapy , Endocrinology/organization & administration , Patient Care Team/organization & administration , Planning Techniques , Communication , Germany , Humans , Interprofessional RelationsABSTRACT
PURPOSE: Recent studies have demonstrated the relevance of (18)F-FDG uptake as an independent prognostic factor for recurrence of operable non-small cell lung cancer (NSCLC). This corresponds with the experimental finding that FDG uptake correlates with the proliferative activity of tumour cells (Higashi et al., J Nucl Med 2000;41:85-92). On the basis of these observations, we studied the influence of FDG uptake on prognosis and occurrence of distant metastases in patients with advanced NSCLC. METHODS: One hundred and fifty-nine patients with NSCLC of UICC stage IIIA or IIIB were included in the study. In all patients, neoadjuvant treatment was planned to achieve operability. FDG PET was performed as an additional staging procedure prior to the initiation of therapy. Clinical outcome data in terms of overall survival, disease-free survival and incidence of distant metastases could be obtained for 137 patients and were correlated with the average standardised uptake value of the tumour (SUV(avg)). Furthermore, other factors influencing SUV(avg) and patient outcome (histological tumour type, grading, UICC stage, tumour size) were analysed. RESULTS: SUV(avg) was significantly influenced by tumour histology, UICC stage and tumour size. No significant difference could be shown for grading. In 38 out of the 159 patients (24%), FDG PET revealed previously unsuspected distant metastases. The incidence of distant metastases significantly correlated with SUV(avg). Overall survival tended to decrease with increasing SUV(avg); however, significance was only reached when a cut-off of 12.0 was applied (p=0.05). CONCLUSION: FDG uptake is an independent prognostic factor in patients with UICC stage III NSCLC, although less distinctively so than has been reported for stage I/II tumours.
Subject(s)
Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/mortality , Fluorodeoxyglucose F18/pharmacokinetics , Image Interpretation, Computer-Assisted/standards , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/mortality , Adult , Aged , Carcinoma, Non-Small-Cell Lung/metabolism , Disease-Free Survival , Humans , Image Interpretation, Computer-Assisted/methods , Incidence , Lung Neoplasms/metabolism , Middle Aged , Outcome Assessment, Health Care/methods , Outcome Assessment, Health Care/statistics & numerical data , Prognosis , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics , Reference Values , Reproducibility of Results , Risk Assessment/methods , Risk Factors , Sensitivity and Specificity , Survival Analysis , Survival RateABSTRACT
BACKGROUND: Diagnosis and treatment of FUO or systemic inflammation with unknown reason are still a great challenge for the treating physician. We used (18)F-FDG-PET for further diagnostic work in patients in whom a diagnosis could not be established despite intensive diagnostic efforts. METHODS/RESULTS: We studied nine patients with (18)F-FDG-PET. Two female patients with known Takayasu's arteritis but undefined disease activity, and seven patients with the clinical suspicion of an underlying large vessel vasculitis. The diagnosis of active vasculitis could be confirmed by the PET-results in eight patients. Active vasculitis could be nearly ruled out in one. The diagnoses could be confirmed by follow-up visits. CONCLUSION: (18)F-FDG-PET is a useful diagnostic tool in patients with unclear systemic inflammation and FUO. Especially when large vessel vasculitis is suspected, further diagnostic work by PET seems to be of benefit. Furthermore, it offers the opportunity to evaluate disease activity and to check which vessels are involved.
Subject(s)
Diagnostic Errors/prevention & control , Fever of Unknown Origin/diagnosis , Fluorodeoxyglucose F18 , Positron-Emission Tomography/methods , Radionuclide Angiography/methods , Systemic Inflammatory Response Syndrome/diagnostic imaging , Vasculitis/diagnostic imaging , Adult , Aged , Female , Fever of Unknown Origin/etiology , Humans , Male , Middle Aged , Radiopharmaceuticals , Reproducibility of Results , Sensitivity and Specificity , Systemic Inflammatory Response Syndrome/etiology , Vasculitis/complicationsABSTRACT
PURPOSE: To evaluate the dose of (188)Re that completely suppresses growth and clonogenic activity of human aortic smooth muscle cells (haSMC) since these cells are mainly responsible for restenosis occurring after PTA. For comparison, growth and clonogenic activity of endothelial cells (EC) were investigated with corresponding doses. MATERIALS AND METHODS: Two days after plating, haSMC and EC were incubated with (188)Re for five days. The doses applied ranged from 4 to 16 Gy. Cell growth was observed for a period of 20 days (EC) or 30 days (haSMC), respectively. Clonogenic activity was monitored over a period of 20 days for both cell lines. RESULTS: Irradiation caused dose-depend-ent inhibition of cell growth and clonogenic activity both in haSMC and in EC. HaSMC growth was completely blocked with 8 Gy, while EC still showed some proliferation even with 16 Gy. The clonal activity of haSMC was also completely blocked with 8 Gy while EC still showed little clonal activity even with 16 Gy. CONCLUSION: Cell growth of both haSMC and EC can be effectively suppressed in a dose-dependent manner. Only haSMC showed a complete growth arrest with 8 Gy while EC were able to proliferate even with 16 Gy. HaSMC colony formation was completely suppressed after application of 8 Gy, while the EC still showed colony formation activity with 16 Gy. (188)Re has some advantageous properties for intravascular irradiation in comparison to other radionuclides making it an interesting radionuclide for stent coating to prevent restenosis.
Subject(s)
Angioplasty, Balloon , Endothelial Cells/radiation effects , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/radiation effects , Radioisotopes/pharmacology , Rhenium/pharmacology , Stents , Aorta/radiation effects , Cell Division/radiation effects , Cell Line , Colony-Forming Units Assay , Constriction, Pathologic/prevention & control , Dose-Response Relationship, Radiation , Endothelial Cells/cytology , Humans , Muscle, Smooth, Vascular/growth & development , Radiation Dosage , Recurrence , Time FactorsABSTRACT
A number of variously monosubstituted 1,n-diaza[n]paracyclophanes (n = 10-12), which show planar chirality and atropisomerism due to hindered rotation about single bonds, were synthesized via a classical route to analyze their stereodynamic properties. Racemic analytes with 10- and 11-membered bridges were resolved by capillary zone electrophoresis (CZE) in acidic phosphate buffers (pH 2.5-4.5) employing permethylated beta- and gamma-cyclodextrin as chiral additives. Moreover, cyclodextrin mediated CZE was used in a discontinuously driven mode for investigations of the rotational interconversion process of conformationally labile homologues (n = 11). In stopped-flow experiments, after baseline separation enantiomers were partially enantiomerized in situ inside the capillary by heating. The rate constants (k(enan) = 1/2 k(rac)) and rotational energy barriers (Delta G(++)) were determined from the resulting enantiomeric ratios. Energy barriers between 113-126 kJ/mol were found depending on the substituent of the benzene ring and the degree of ionization of the amino groups in bridgehead positions. The energy barriers increased in order of the substituents: NO(2) >> CF(3) > Br > Cl > CH(3) approximately F. In addition, the rotational energy barriers were decreased by approximately 6-8 kJ/mol in the presence of the chiral selector.
ABSTRACT
The reliable assessment of residual masses after treatment as well as of new lesions suspected for relapse remains a diagnostic problem in patients with Hodgkin's disease (HD). The current study compares the results obtained by CT scan to FDG-PET imaging in a blind analysis with respect to the viability of residual masses and in case of suspected relapse. Between 1/94 and 10/99, 47 comparisons of PET and corresponding CT scans - 26 comparisons in 24 patients with residual tumors and 21 comparisons in 20 patients with suspected relapse of HD - were evaluated by independent reviewers blinded to he results of each other. Patients with primary diagnosis had been treated within trials of the German HD Trial study group. Relapsed patients received intensified salvage chemotherapy regimens. PET was assessed visually and by quantifying glucose uptake (SUV). Changes in size of tumor lesions as well as contrast medium enhancement served as criteria for assessment by CT scans. Results were validated either by histologic examination of a resected mass or biopsy (n=17) or by a clinical follow-up over 6 months following treatment (n=30). In 26 cases with residual lesions FDG-PET showed an increased tracer uptake in 8, 7 of which were true positive (TP) and 1 false positive (FP). Eighteen cases were classified as being negative (no viable HD), 17 true negative (TN) and 1 FN. In the blinded reading of the corresponding CT scans, 10 cases with residual lesions were considered to contain vital lymphoma (2 TP, 8 FP). Sixteen CT scans were classified as negative (10 TP, 6 FN). The resulting sensitivity and specificity of PET were 87.5% and 94.4% in contrast to only 25% and 56% for CT scans. The positive and negative predictive values of PET and CT scans were 87.5% and 94.4% and 20% and 62.5%, respectively. In patients with suspected relapse, sensitivity and positive predictive value for the diagnosis of the relapse were 100% and 86%, respectively, yielding the same results for both methods. FDG-PET performed in HD patients with residual masses appears to offer important additional information regarding the presence of viable HD in these residual lesions. In patients with suspected relapse of HD, FDG-PET seems not to offer any information over CT scans. Using SUVs is not superior to visual assessment of PET alone.
Subject(s)
Hodgkin Disease/diagnostic imaging , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm, Residual/diagnostic imaging , Tomography, Emission-Computed , Tomography, X-Ray Computed , Adult , Female , Fluorodeoxyglucose F18 , Humans , Male , Middle Aged , Predictive Value of Tests , RadiopharmaceuticalsABSTRACT
PURPOSE: To evaluate dose-dependent growth-modulating effects of the beta-gamma emitter Rhenium-188 on cultured human aortic smooth muscle cells (haSMC). METHODS AND MATERIALS: HaSMC were plated in 25 cm(2) flasks. Two days after plating, cells were incubated with the Re-188 (beta E(max) 2.12 MeV, tissue range(max) < 10 mm, T(1/2) 17 h) for five days. The doses administered were 0.2 Gy, 1, 4, 6, 8, 16, and 32 Gy. After five days, the radionuclide was removed. Cell growth, cell cycle distribution, and clonogenic activity were analyzed for the following 25 days. RESULTS: The 0.2 and 1 Gy groups did not show relevant growth-inhibiting effects compared to the control groups. The 4 to 32 Gy groups presented dose-dependent growth inhibition, with a complete growth arrest of the 16 and 32 Gy groups. Clonogenic activity of the smooth muscle cell was strongly inhibited from doses > or =8 Gy. Flow cytometry showed a lasting dose-dependent G2/M phase block. CONCLUSION: Smooth muscle cell (SMC) growth can be controlled effectively with Re-188 for at least 25 days after radiation in vitro. As the first four weeks after arterial angioplasty are crucial concerning neointimal formation, Re-188 may be a valuable radionuclide to inhibit restenosis after arterial angioplasty.
Subject(s)
Aorta/radiation effects , Cell Division/radiation effects , Muscle, Smooth, Vascular/radiation effects , Radioisotopes/pharmacology , Rhenium/pharmacology , Aorta/cytology , Dose-Response Relationship, Drug , Humans , Interphase/radiation effects , Muscle, Smooth, Vascular/cytology , RadiobiologyABSTRACT
PURPOSE: The aim of this study was to evaluate the capability of human aortic smooth musc e cells (HaSMC) and endothelial cells (EC) to recover after incubation with the combined beta/gamma emitter 186rhenium. MATERIALS AND METHODS: Two days after plating, HaSMC and EC were incubated for five days with 186Re (total doses applied 4 Gy-32 Gy). Cell counts were performed for a period of 30 days (haSMC) and 22 days (EC). To detect possible growth recovery, colony formation assays were plated for both cell types on day 5, 10, and 20 (and lay 30 for haSMC). RESULTS: Both cell types presented a dose-dependent growth inhibition which was maximum at a dose of 32 Gy. Human endothelial cells presented with total growth recovery at 4 and 8 Gy, and a partial growth recovery at 16 Gy. Smooth muscle cells only presented partial growth recovery at 4 and 8 Gy. At 16 Gy and more no recovery was detected. CONCLUSION: HaSMC as well as EC growth can be modulated effectively with 186Re over a period of 30 days in vitro. Compared to smooth muscle cells human endothelial cellls seem to possess a higher potential to recover at doses of 8 to 16 Gy. 186Re may be a valuable radionuclide to prevent restenosis.
Subject(s)
Endothelium, Vascular/cytology , Endothelium, Vascular/radiation effects , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/radiation effects , Radioisotopes/pharmacology , Rhenium/pharmacology , Angioplasty, Balloon , Angioplasty, Balloon, Coronary , Aorta/cytology , Cell Count , Cell Division , Cells, Cultured , Humans , Radiation Dosage , Recurrence , Time FactorsABSTRACT
Heptakis(6-O-tert-butyldimethylsilyl-2,3-di-O-methyl)cyclomaltohep taose (6-TBDMS-2,3-Me-beta-CD) and heptakis(2,3,6-tri-O-methyl)cyclomaltoheptaose (per-Me-beta-CD) were monofunctionalized by introduction of a 5-cyanopentyl group attached to one of the O-2, O-3 or O-6 positions and subsequent reduction with lithium aluminum hydride to give the corresponding mono-O-(omega-aminohexyl) derivatives. Alternatively, after attachment of a 7-octenyl group and further epoxidation the corresponding mono-omega-epoxyoctyl derivatives of 6-TBDMS-2,3-Me-beta-CD were obtained. The mono-O-(omega-aminohexyl) derivatives were immobilized by reaction with glycidoxypropyl and 'aldehyde' silica, whereas aminopropyl silica was used for the immobilization of the monoepoxyoctyl derivatives. The immobilized cyclodextrin derivatives were partially evaluated as chiral stationary phases in high-performance liquid chromatography (HPLC) and micro-HPLC.