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1.
J Clin Oncol ; 28(23): 3709-16, 2010 Aug 10.
Article in English | MEDLINE | ID: mdl-20625137

ABSTRACT

PURPOSE: Fractionated radioimmunotherapy targeting CD22 may substantially improve responses and outcome in non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: A multicenter trial evaluated two or three weekly infusions of yttrium-90 ((90)Y) epratuzumab tetraxetan (humanized anti-CD22 antibody) in 64 patients with relapsed/refractory NHL, including 17 patients who underwent prior autologous stem-cell transplantation (ASCT). Objective (OR) and complete responses (CR/complete response unconfirmed [CRu]), as well as progression-free survival (PFS), were determined. RESULTS: At the maximum total (90)Y dose of 45 mCi/m(2) (1,665 MBq/m(2)), grade 3 to 4 hematologic toxicities were reversible to grade 1 in patients with less than 25% bone marrow involvement. The overall OR rate and median PFS for all 61 evaluable patients was 62% (CR/CRu, 48%) and 9.5 months, respectively. Patients without prior ASCT obtained high OR rates of 71% (CR/CRu, 55%) across all NHL subtypes and (90)Y doses, even in poor-risk categories (refractory to last anti-CD20-containing regimen, 73% [CR/CRu, 60%]; bulky disease: 71% [CR/CRu, 43%]). Patients with prior ASCT received lower doses, but achieved an OR rate of 41% (CR/CRu, 29%). For patients with follicular lymphoma (FL), OR rates and median PFS increased with total (90)Y-dose, reaching 100% (CR/CRu, 92%) and 24.6 months, respectively, at the highest dose levels (> 30 mCi/m(2) total (90)Y-dose [1,110 MBq/m(2)]). Further, patients with FL refractory to prior anti-CD20-containing regimens achieved 90% (nine of 10 patients) OR and CR/CRu rates and a median PFS of 21.5 months. CONCLUSION: Fractionated anti-CD22 radioimmunotherapy provides high total doses of (90)Y, yielding high rates of durable CR/CRus in relapsed/refractory NHL, resulting in 20 mCi/m(2) x 2 weeks as the recommended dose for future studies.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Antineoplastic Agents/administration & dosage , Lymphoma, Non-Hodgkin/therapy , Radioimmunotherapy , Yttrium Radioisotopes/administration & dosage , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized , Female , Humans , Male , Middle Aged , Treatment Outcome , Young Adult
2.
Nucl Med Biol ; 36(7): 833-43, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19720295

ABSTRACT

INTRODUCTION: (13)C, (18)F and (123)I fatty acids (FA) are used for myocardial imaging. Recently, our group showed that [(99m)Tc]-labeled "4+1" FA are extracted into the rat and guinea pig myocardium. The present study evaluates determinants of myocardial uptake and whole body biodistribution of these FA derivatives. METHODS: Studies were performed with isolated perfused hearts of Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) with a FAT/CD36 deficiency, as well as with heart type FA binding protein knockout mice (H-FABP)(-/-) and H-FABP(+/+). Eight 4+1-(99m)Tc-FA were applied for 3 min followed by 1-min washout. A mathematical model was used to analyze FA dynamics and binding to proteins. Whole-body distribution was studied in rats with and without Tween 80. In vitro fractionation studies with [(99m)Tc]-FA assessed red blood cell uptake as well as association with plasma lipoproteins very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). RESULTS: Myocardial extraction was 19.0-33.0% of the infused dose in isolated WKY and 15.2-26.4% in SHR hearts. However, H-FABP(-/-) showed a marked reduction of tracer extraction [2.8+/-0.6%ID (percent injected dose) vs. 17+/-2%ID P<.001]. Uptake in red blood cells (<1.2%ID) and incorporation into lipoproteins were negligible. Incubation of (99m)Tc-FA with albumin reduced ventricular extraction (P<.001) into the range of established iodinated FA tracers. polyoxyethylene(20) sorbitan monooleate improved the heart-to-liver ratio in the biodistribution studies. CONCLUSIONS: Myocardial uptake of [(99m)Tc]-FA 4+1 derivatives is dependent on H-FABP. These substances may therefore provide a new tool to specifically assess regional myocardial changes of H-FABP.


Subject(s)
Fatty Acids/metabolism , Fatty Acids/pharmacokinetics , Myocardial Perfusion Imaging , Myocardium/metabolism , Organotechnetium Compounds/chemistry , Animals , Biological Transport/drug effects , CD36 Antigens/metabolism , Cattle , Cytosol/metabolism , Erythrocytes/metabolism , Fatty Acid Binding Protein 3 , Fatty Acid-Binding Proteins/metabolism , Fatty Acids/chemistry , Female , Heart/diagnostic imaging , Heart/drug effects , Heart/physiology , Heart Ventricles/metabolism , Hemodynamics , Humans , In Vitro Techniques , Intracellular Space/metabolism , Isotope Labeling , Lipid Metabolism , Male , Mice , Models, Biological , Myocardium/cytology , Rats , Reproducibility of Results , Serum Albumin, Bovine/pharmacology , Tissue Distribution
3.
Nucl Med Biol ; 36(7): 845-52, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19720296

ABSTRACT

INTRODUCTION: Our group has synthesized technetium-labeled fatty acids (FA) that are extracted into the myocardium and sequestered due to heart-type fatty acid binding protein (H-FABP) binding. In this article, we further address the detailed subcellular distribution and potential myocardial metabolism of [(99m)Tc]"4+1" FA. METHODS: Experiments were conducted using isolated hearts of Wistar rats, as well as of wild-type and H-FABP(-/-) mice. Myocardium samples underwent subcellular fractionation [subsarcolemmal mitochondria (SM), intermyofibrillar mitochondria (IM), cytosol with microsomes, and nuclei and crude membranes] and analysis by thin-layer chromatography and high-performance liquid chromatography. RESULTS: The largest fraction of tissue radioactivity was associated with cytosol [79.69+/-8.88% of infused dose]. About 9.07+/-0.95% and 3.43+/-1.38% of the infused dose were associated with SM and IM fractions, respectively. In the rat heart, etomoxir, an inhibitor of carnitin-palmitoyl transferase I, did not significantly decrease radioactivity associated with mitochondrial fractions, whereas myocardial extraction of [(123)I]-labeled 15-(p-iodophenyl)-pentadecanoic acid (13.26% vs. 49.49% in controls) and the radioactivity associated with the SM and IM fractions were blunted. The percentage of the infused dose in the mitochondrial and crude fractions increased with the number of NH-amide groups of the FA derivative. Absence of H-FABP significantly decreased radioactivity count in the cytosolic fraction (P<.001). No metabolic product of [(99m)Tc]"4+1" FA could be detected in any isolated heart. CONCLUSIONS: Myocardial [(99m)Tc]"4+1" FA extraction reflects binding to H-FABP and membrane structures (including the mitochondrial membrane). However, the compounds do not undergo mitochondrial metabolism because they do not reach the mitochondrial matrix.


Subject(s)
Fatty Acids/chemistry , Fatty Acids/metabolism , Intracellular Space/metabolism , Myocardial Perfusion Imaging , Myocardium/cytology , Myocardium/metabolism , Organotechnetium Compounds/chemistry , Amides/chemistry , Animals , Biological Transport/drug effects , Carnitine O-Palmitoyltransferase/antagonists & inhibitors , Carnitine O-Palmitoyltransferase/metabolism , Cattle , Enzyme Inhibitors/pharmacology , Epoxy Compounds/pharmacology , Fatty Acid Binding Protein 3 , Fatty Acid-Binding Proteins/metabolism , Fatty Acids/chemical synthesis , Female , Heart/diagnostic imaging , Heart/drug effects , In Vitro Techniques , Intracellular Space/drug effects , Isotope Labeling , Male , Mice , Mitochondria/metabolism , Rats , Reproducibility of Results
4.
Ann Nucl Med ; 23(1): 1-16, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19205833

ABSTRACT

Lung perfusion scintigraphy (LPS) with technetium-99m-labeled macro-aggregates of albumin (Tc-99m-MAA) is well established in the diagnostic of pulmonary embolism (PE). In the last decade, it was shown that single-photon emission computer tomography (SPECT) acquisition of LPS overcame static scintigraphy. Furthermore, there are rare indications for LPS, such as preoperative quantification of regional lung function prior to lung resection or transplantation, optimization of lung cancer radiation therapy, quantification of right-left shunt, planning of intra-arterial chemotherapy, and several rare indications in pediatrics. Moreover, LPS with Tc-99m-MAA is a safe method with low radiation exposure. PE can also be diagnosed by spiral computer tomography (CT), ultrasound, magnetic resonance angiography, or pulmonary angiography (PA, former gold standard). The present review considers all these methods, especially spiral CT, and compares them with LPS with respect to sensitivity and specificity and gives an overview of established and newer publications. It shows that LPS with Tc-99m-MAA represents a diagnostic method of continuing value for PE. In comparison with spiral CT and/or PA, LPS is not to be defeated as mentioned also by the most actual Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) II reports. This applies in particular to chronic or recurring embolisms, whereas currently spiral CT may be of greater value for major or life-threatening embolisms. At present, LPS cannot be replaced by other methods in some applications, such as pediatrics or in the quantification of regional pulmonary function in a preoperative context or prior to radiation therapy. LPS still has a place in the diagnostics of PE and is irreplaceable in several rare indications as described earlier.


Subject(s)
Lung/diagnostic imaging , Pulmonary Embolism/diagnostic imaging , Radiopharmaceuticals/administration & dosage , Technetium Tc 99m Aggregated Albumin/administration & dosage , Tomography, Emission-Computed, Single-Photon/methods , Administration, Inhalation , Humans , Injections, Intravenous , Isotope Labeling/methods
5.
Bioconjug Chem ; 19(1): 97-108, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18052115

ABSTRACT

Our group previously synthesized 99m Tc-labeled fatty acids suitable for myocardial metabolism and flow imaging. In this set of experiments, 29 new analogues were synthesized according to the "4 + 1" mixed ligand approach with some specific differences. Conventional "4 + 1" 99m Tc-fatty acids are built in the sequence: Tc-chelate, alkyl chain, and carboxylic group. We developed compounds following a new design with the sequence: carboxylic group, alkyl chain, Tc-chelate, and lipophilic tail. Therefore, the 99m Tc-chelate was transferred to a more central position of the compound, aiming toward an improved myocardial profile and an accelerated liver clearance. In this context, several functional groups incorporated in the lipophilic tail section were tested to evaluate their influence on the compound's character. In addition to biodistribution studies in vivo, the myocardial first-pass extraction of the compounds was tested in an isolated Langendorff rat heart model. A satisfactory myocardial uptake of up to 20% of the injected dose (% ID) in the perfused heart and a fast liver clearance in vivo with only 0.29% ID/g at 60 min postinjection demonstrate that the induced molecular modifications affect the kinetics of 99m Tc-radiolabeled fatty acid compounds favorably. From the data set, rules for estimating the biodistribution of fatty acids tracers are deduced.


Subject(s)
Fatty Acids/chemistry , Fatty Acids/metabolism , Myocardium/metabolism , Technetium/chemistry , Animals , Carboxylic Acids/chemistry , Chelating Agents/chemistry , Crystallography, X-Ray , Fatty Acids/analysis , Female , Kinetics , Ligands , Male , Models, Molecular , Molecular Conformation , Perfusion , Rats , Rats, Wistar , Rhenium/chemistry
6.
Nucl Med Commun ; 28(8): 637-45, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17625386

ABSTRACT

PURPOSE: In an effort to develop 99mTc-labelled fatty acids (FAs) for myocardial metabolism and flow imaging, several Tc analogues according to the '3+1' and the '4+1' mixed-ligand approach were synthesized and myocardial extraction was evaluated in non-working isolated guinea pig hearts. An example of biodistribution patterns in guinea pigs was determined by using one FA analogue. METHODS: The coordination moieties contain a +5, respectively +3, oxidation state metal core attached to the end position of a FA chain. FA complexes of the '3+1' and the '4+1' mixed-ligand type were prepared and investigated using the isolated heart model. To estimate the diagnostic value of the analogue 99mTc-FAs, the biodistribution of one well-extracted FA was evaluated. RESULTS: The '4+1' FA compounds achieved the highest uptake rates of all the technetium FAs investigated. In particular, the '4+1' 99mTc-C11-FA achieved at least a 2-fold higher ventricular extraction of the applied activity than the established control tracers including omega-(p-[123I]iodophenyl)pentadecanoic FAs (BMIPP and IPPA) and Tc-MIBI. Furthermore, the '4+1' dodecanoic FA derivative and the thiadodecanoic FA derivative showed an extraction comparable to established 123I-labelled tracers. Biodistribution experiments performed for the thiadodecanoic FA derivative indicated a good heart/blood and heart/lung ratio and also a high uptake in the liver. In contrast, '3+1' 99mTc complexes showed a low myocardial extraction rate. Nevertheless, the differentiation in the extraction profile, which depends on the FA chain length and structure, indicates a specific heart uptake of these 99mTc-labelled FA derivatives as well. CONCLUSIONS: The excellent extraction rates found for '4+1' 99mTc-FAs indicate possibly promising structures for innovative myocardial tracers.


Subject(s)
Fatty Acids/pharmacokinetics , Myocardium/metabolism , Radiopharmaceuticals/pharmacokinetics , Technetium/pharmacokinetics , Animals , Guinea Pigs , Heart/physiology
7.
Bioconjug Chem ; 18(1): 216-30, 2007.
Article in English | MEDLINE | ID: mdl-17226976

ABSTRACT

Technetium-labeled fatty acids intended for myocardial metabolism imaging and the respective rhenium model complexes were synthesized according to the "4 + 1" mixed-ligand approach and investigated in vitro and in vivo. The non-radioactive rhenium model complexes were characterized by NMR, IR, and EA, and the geometrical impact of the chelate unit on the integrity of the fatty acid head structure was determined by single-crystal X-ray analyses. To estimate the diagnostic value of the 99mTc-labeled fatty acids, the compounds were investigated in experiments in vitro and in biodistribution studies using male Wistar rats. The new fatty acid tracers contain the metal core in the oxidation states +3, well-wrapped in a trigonal-bipyramidal coordination moiety, which is attached at the omega-position of a fatty acid chain. This structural feature is considered to be a good imitation of the well-established iodinated phenyl fatty acids. High heart extraction in perfused heart studies (up to 26% injected dose (ID)) and noticeable heart uptake of the 99mTc tracers in vivo being in the order of 2% ID/g at 5 min (postinjection, pi.), accompanied by a good heart to blood ratio of 8, confirms that the new Tc compounds are suitable as fatty acid tracers.


Subject(s)
Fatty Acids/chemistry , Fatty Acids/metabolism , Myocardium/metabolism , Technetium/chemistry , Animals , Copper/chemistry , Crystallography, X-Ray , Fatty Acids/chemical synthesis , Fatty Acids/pharmacokinetics , Heart/drug effects , Ligands , Male , Models, Molecular , Molecular Structure , Rats , Rats, Wistar , Spectroscopy, Fourier Transform Infrared
8.
Coron Artery Dis ; 17(4): 371-7, 2006 May.
Article in English | MEDLINE | ID: mdl-16707961

ABSTRACT

BACKGROUND: In cases of in-stent restenosis, intracoronary radiotherapy with beta-emitters and gamma-emitters has been shown to reduce the risk of repeat restenosis. The present randomised, placebo-controlled study addresses the question of whether intracoronary radiotherapy applied by the easy-to-handle Rhenium liquid-filled angioplasty balloon system is also able to reduce the angiographic re-restenosis rate in stents. METHODS AND RESULTS: At our center, from May 2000 to December 2003, 165 patients (mean age 64+/-10, median 65 years; 127 men, 38 women) with symptomatic in-stent restenosis underwent either intracoronary brachytherapy or sham procedure. Index clinical and angiographic parameters were largely comparable in both groups. Radiation therapy was performed with a standard percutaneous transluminal coronary angioplasty (PTCA) balloon catheter inflated with liquid Rhenium in the redilated in-stent restenosis for 240-890, mean 384+/-125 s with low pressure (3 atm) in order to reach 30 Gy at 0.5 mm depth of the vessel wall. In 82 patients, intracoronary radiotherapy was carried out without complications, but one of the 83 patients who underwent sham procedure suffered small myocardial infarction. During follow-up, stent thrombosis with subsequent non-Q-wave myocardial infarction occurred in one patient in each group (6 days and 8 months after the procedure, respectively). At 6 months after the index procedure, repeat angiography was performed in 156 of the 164 patients with successful procedure (rate 95%): restenosis (stenosis >50% in diameter) or reocclusion was observed in only 19 of 78 (=24%) patients of the radiation but in 31 of 78 (=40%) patients of the sham procedure group (P=0.04). Event-free survival (free of death, myocardial infarction, target vessel revascularization) at 1 year was 87% for patients being radiated and 74% for patients having undergone sham procedure (P=0.05). CONCLUSIONS: Intracoronary radiation therapy with the liquid-filled beta-emitting Rhenium balloon is not only easy to perform, safe, and comparably inexpensive but also an effective option to prevent repeat restenosis and the need for target vessel revascularization in cases of in-stent restenosis.


Subject(s)
Angioplasty, Balloon, Coronary/methods , Coronary Restenosis/radiotherapy , Rhenium/therapeutic use , Aged , Double-Blind Method , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Radioisotopes , Treatment Outcome
9.
Helicobacter ; 9(6): 629-31, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15610076

ABSTRACT

BACKGROUND: Lymphocytic gastritis is a rare condition found in approximately 1% of dyspeptic patients. An association with Helicobacter pylori infection has been described. Hypertrophic lymphocytic gastritis is a rare cause of gastrointestinal protein loss. Here, we describe a patient with hypertrophic lymphocytic gastritis, in whom gastrointestinal protein loss resolved completely following H. pylori eradication. CASE REPORT: A 38-year old obese man without gastrointestinal symptoms showed a markedly decreased serum protein (53 g/l, normal 66-85 g/l), a decreased serum albumin (33 g/l, normal 35-52 g/l) and decreased serum immunoglobulin G and immunoglobulin M levels. A renal cause for protein loss was excluded, liver function was normal. Endoscopy of the upper gastrointestinal tract revealed enlarged rigid gastric folds, and an H. pylori-associated lymphocytic gastritis. 99mTc-labelled albumin scintigraphy showed an increased activity in the upper left abdomen compatible with protein secretion in the stomach, and tracer pooling in the upper small bowel. Push enteroscopy with histology demonstrated a normal upper small bowel. Two months after eradication therapy, cure of H. pylori infection was documented and serum protein (71 g/l) and albumin (41 g/l) had returned to normal, while lymphocytic gastritis was still present. One year after eradication therapy endoscopy of the upper gastrointestinal tract and histology and laboratory values were normal. CONCLUSION: Protein-losing gastropathy caused by H. pylori-associated hypertrophic lymphocytic gastritis can be cured solely by H. pylori eradication therapy.


Subject(s)
Gastric Mucosa/metabolism , Gastritis, Hypertrophic/metabolism , Helicobacter Infections/metabolism , Intestinal Mucosa/metabolism , Proteins/metabolism , Adult , Blood Proteins/metabolism , Endoscopy, Gastrointestinal , Gastritis, Hypertrophic/drug therapy , Gastritis, Hypertrophic/microbiology , Helicobacter Infections/complications , Helicobacter Infections/drug therapy , Helicobacter pylori , Humans , Kidney Function Tests , Liver Function Tests , Male , Radiography, Abdominal
10.
Mov Disord ; 19(10): 1196-202, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15390014

ABSTRACT

Olfactory loss is among the early signs of Parkinson's disease (PD). We investigated whether "idiopathic" olfactory dysfunction might relate to signs of nigral degeneration. Olfactory tests were combined with transcranial sonography of the substantia nigra and single photon emission computed tomography (SPECT) imaging. Thirty patients diagnosed with idiopathic olfactory loss participated. Eleven of these patients exhibited an increased echogenicity of the SN in the transcranial sonography. In 10 of these 11 patients, SPECT scans with (123)I-FP-CIT were performed. Median uptake ratios in the basal ganglia were pathological in 5 patients, 2 patients exhibited borderline findings, and 3 patients had normal results. Considering patients with idiopathic olfactory dysfunction, noninvasive transcranial sonography seems to be helpful in identifying patients potentially at risk to develop PD. Longitudinal follow-up studies are necessary to estimate the ratio of patients with dopaminergic cell loss in the basal ganglia who will develop PD in the future.


Subject(s)
Echoencephalography/methods , Olfaction Disorders/diagnosis , Olfaction Disorders/etiology , Parkinson Disease/diagnosis , Tomography, Emission-Computed, Single-Photon , Adult , Aged , Female , Humans , Iodine Radioisotopes , Male , Middle Aged , Parkinson Disease/complications , Predictive Value of Tests , Prospective Studies , Radiopharmaceuticals , Severity of Illness Index , Tropanes
11.
Int J Cardiol ; 95(1): 29-34, 2004 May.
Article in English | MEDLINE | ID: mdl-15159034

ABSTRACT

BACKGROUND: Intracoronary radiotherapy with beta- and gamma-emitters has been shown to reduce the risk of restenosis after balloon angioplasty and after coronary stenting. The present study addresses the question whether intracoronary radiotherapy using the (188)rhenium liquid-filled PTCA balloon system is feasible, safe and effective in cases of in-stent restenosis. Acute and long-term angiographic results as well as clinical events within 1 year after the procedure were evaluated. METHODS AND RESULTS: From September 1999 to April 2000, 41 patients (mean age 60+/-10 years, 33 male, 8 female) with symptomatic in-stent restenosis underwent repeat PTCA and immediate intracoronary brachytherapy. After successful repeat PTCA (residual stenosis less than 30% in diameter), a second standard PTCA catheter was inflated with liquid (188)rhenium in the redilated in-stent restenosis for 315-880, mean 540+/-155 s with low pressure (3 atm) in order to reach 30 Gy at 0.5 mm depth of the vessel wall. In all patients with successful reintervention, intracoronary radiotherapy was unproblematically performed; in 16 patients, 21 new stents were implanted during the procedure-either immediately before or after radiation therapy. During follow-up, four episodes of stent thrombosis with subsequent myocardial infarction occurred in three patients (8 days, 37 days, 5 months and 6 months after the procedure, respectively). This complication was seen exclusively in patients with newly implanted stents. One patient of the stent group died suddenly 46 days after the procedure. All 40 surviving patients underwent repeat angiography in cases of repeat angina or routinely 6 months after brachytherapy, respectively. In the redilated target vessels without new stenting, restenosis (stenosis >50% in diameter) or reocclusion was observed in only 5 of 25 (=20%) cases, but in the restented target lesions, in 10 of 15 (=67%). Event-free survival (death, myocardial infarction, TVR) at 1 year after repeat dilatation and subsequent brachytherapy was 80% for patients not newly stented, but only 44% for patients with new stents. CONCLUSIONS: Intracoronary radiation therapy with the liquid-filled beta-emitting (188)rhenium balloon is a safe and effective therapy in cases of in-stent restenosis. The positive effect of irradiation, however, is abolished if a new stent is needed. In the not newly stented patients, 1-year follow-up is encouraging.


Subject(s)
Angioplasty, Balloon, Coronary , Brachytherapy , Coronary Restenosis/therapy , Radioisotopes/therapeutic use , Rhenium/therapeutic use , Aged , Combined Modality Therapy , Coronary Angiography , Coronary Restenosis/diagnostic imaging , Coronary Vessels/radiation effects , Coronary Vessels/surgery , Feasibility Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Complications/diagnostic imaging , Postoperative Complications/etiology , Postoperative Complications/mortality , Retrospective Studies , Survival Analysis , Time , Time Factors , Treatment Outcome
12.
Clin Cardiol ; 26(11): 525-9, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14640469

ABSTRACT

BACKGROUND: An increasing number of clinical studies indicates reduction of angina and myocardial ischemia by enhanced external counterpulsation (EECP) therapy. However, given the wide range of contraindications and the long duration of treatment, eligibility and practicality issues have not been addressed systematically. HYPOTHESIS: Of all candidates for EECP (patients with drug-refractory angina without possibility of revascularization), the majority either have contraindications or have practical problems complying with the time demands that this therapy imposes. In the rest, EECP leads to satisfactory results. METHODS: During 18 months, every consecutive patient with angina despite medical and interventional therapy was evaluated for EECP at one center. Treated patients underwent a bicycle exercise test and perfusion imaging before and after the standard course of 35 h of EECP. In addition, patients were asked about frequency of angina and nitroglycerin usage before and after EECP, and all patients filled out a final questionnaire 1 year after the end of therapy. RESULTS: Overall, 48 patients were considered candidates for EECP. Of these, 24 were excluded for medical reasons: poor ejection fraction (4), peripheral artery disease (4), anticoagulation (4), and atrial fibrillation (3). Eight further patients declined EECP for lack of time or accommodation. Another 3 of the 16 remaining patients dropped out because of side effects. In the 13 patients who finished the treatment course, weekly anginal episodes were reduced by 48% (p < 0.05), on-demand nitroglycerin puffs were reduced by 51% (p < 0.05), work capacity was improved by 22% (p < 0.05), and the number of reversible perfusion defects in perfusion scans decreased nonsignificantly (-28%). However, 4 of 13 treated patients determined 1 year later that the detriment of loss of time exceeded the benefits of EECP. CONCLUSION: Similar to previous reports, our study confirms the reduction of angina and improvement of work capacity after EECP. However, using established contraindications, approximately two-thirds of patients considered to be candidates had to be excluded, and one-third of the treated patients regarded EECP therapy retrospectively as too time consuming.


Subject(s)
Angina Pectoris/surgery , Counterpulsation , Exercise Test , Female , Humans , Male , Middle Aged , Nitroglycerin/therapeutic use , Treatment Outcome , Vasodilator Agents/therapeutic use
13.
J Nucl Med ; 44(6): 953-60, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12791825

ABSTRACT

UNLABELLED: 188Re-Hydroxyethylidene diphosphonate ((188)Re-HEDP) was used in previous studies for the palliative treatment of metastatic bone pain. However, the kinetic and radiation-absorbed doses have not been well documented. Therefore, the aim of this study was to gather dosimetric data for (188)Re-HEDP. METHODS: Thirteen prostate cancer patients with skeletal involvement were treated with 2,700-3,459 MBq (mean dose, 3,120 MBq) (188)Re-HEDP. Patients underwent whole-body scans 3, 20, and 28 h after therapy. The effective half-life, residence time, and radiation-absorbed dose values were calculated for the whole body, bone marrow, kidneys, and bladder as well as for 29 bone metastases. The urinary excretion rate was determined in 6 urine samples of each patient collected over 48 h at 8-h intervals beginning immediately after the administration of (188)Re-HEDP. After injection of (188)Re-HEDP, blood samples were taken weekly for 6 wk, and platelet and leukocyte counts were performed. RESULTS: The mean effective half-life was 15.9 +/- 3.5 h in bone metastases, 10.9 +/- 2.1 h in the bone marrow, 11.6 +/- 2.1 h in the whole body, 12.7 +/- 2.2 h in the kidneys, and 7.7 +/- 3.4 h in the bladder. The following radiation-absorbed doses were calculated: 3.83 +/- 2.01 mGy/MBq for bone metastases, 0.61 +/- 0.21 mGy/MBq for the bone marrow, 0.07 +/- 0.02 mGy/MBq for the whole body, 0.71 +/- 0.22 mGy/MBq for the kidneys, and 0.99 +/- 0.18 mGy/MBq for the bladder. (188)Re-HEDP showed a rapid urinary excretion within the first 8 h after therapy, with 41% of the (188)Re-HEDP administered being excreted. Forty-eight hours after therapy, the excretion rate was 60% +/- 12%. Only 1 patient showed a decrease of platelet count below 100 x 10(9) counts/L. None of the patients presented with a decrease of leukocyte count below 3.0 x 10(9) counts/L. CONCLUSION: (188)Re-HEDP is an effective radiopharmaceutical used in the palliative treatment of metastatic bone pain. The radiation-absorbed dose is acceptable for bone pain palliation with low doses for the normal bone marrow and the whole body.


Subject(s)
Bone Neoplasms/metabolism , Bone Neoplasms/secondary , Etidronic Acid/pharmacokinetics , Prostatic Neoplasms/pathology , Rhenium/pharmacokinetics , Whole-Body Counting/methods , Aged , Aged, 80 and over , Body Burden , Bone Marrow/metabolism , Etidronic Acid/administration & dosage , Etidronic Acid/blood , Etidronic Acid/urine , Half-Life , Humans , Injections, Intravenous , Kidney/metabolism , Male , Metabolic Clearance Rate , Middle Aged , Organometallic Compounds , Radiation Dosage , Radiometry/methods , Rhenium/administration & dosage , Rhenium/blood , Rhenium/urine , Tissue Distribution , Urinary Bladder/metabolism
14.
Eur J Endocrinol ; 148(4): 395-402, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12656659

ABSTRACT

OBJECTIVES: To evaluate the effectiveness of isotretinoin for improving (131)I uptake in recurrent/metastasized thyroid cancer with no/insufficient (131)I uptake. DESIGN: Retrospective analysis of 25 patients treated between June 1999 and May 2001. METHODS: 15 female and 10 male patients were given isotretinoin at 1 mg/kg for 3 months, followed by (131)I treatment. All patients received a (131)I scan 72 h after administration, thyroglobulin measurement, chest X-ray and ultrasound of the neck, and some patients underwent a (18)F-fluorodeoxyglucose (FDG) positron emission tomography (n=14) and computed tomography scan of the chest (n=11). RESULTS: In two out of 14 patients with raised thyroglobulin but no (131)I uptake, a slightly improved (131)I uptake was seen. In a further 11 patients an improvement of (131)I uptake of known lesions was desired or further non-(131)I-accumulating lesions were known. A dosimetrically relevant improvement of uptake was seen in three of these patients. (18)F-FDG uptake and thyroglobulin did not correlate with the success/failure of the isotretinoin treatment. Side effects including a strong "sunburn", cheilitis, mucositis, conjunctivitis and raised transaminases occurred in two-thirds of patients. They were of an overall tolerable level and were reversible after isotretinoin had been stopped. CONCLUSION: From our clinical experience over a period of 2 years we conclude that the therapeutic effect of isotretinoin in thyroid cancer is certainly less than previously reported. An indiscriminate use of isotretinoin in all patients with otherwise untreatable thyroid cancer cannot be recommended.


Subject(s)
Iodine Radioisotopes/pharmacokinetics , Isotretinoin/administration & dosage , Thyroid Neoplasms/radiotherapy , Adenocarcinoma, Follicular/diagnostic imaging , Adenocarcinoma, Follicular/radiotherapy , Adult , Aged , Aged, 80 and over , Carcinoma, Papillary/diagnostic imaging , Carcinoma, Papillary/radiotherapy , Female , Fluorodeoxyglucose F18 , Humans , Iodine Radioisotopes/therapeutic use , Isotretinoin/adverse effects , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local , Retrospective Studies , Thyroid Neoplasms/diagnostic imaging , Tomography, Emission-Computed , Treatment Outcome
15.
Clin Lymphoma ; 3(2): 121-4, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12435286

ABSTRACT

Positron emission tomography (PET) with [18F]fluorodeoxyglucose [18F]FDG has evolved as a method of increasingly clinical importance in the management of patients with malignant lymphoma. However, inflammatory lesions also accumulate [18F]FDG and may cause difficulties with interpretation. This report deals with 2 patients with simultaneous occurrence of Hodgkin's lymphoma and eosinophilic granuloma, a rare but known coincidence of diseases. In the first case, Hodgkin's disease could not be differentiated from eosinophilic granuloma. Positron emission tomography showed increased [18F]FDG uptake both in lymphoma manifestations and in the granuloma. In the second case with proven Hodgkin's disease, post-treatment examination showed a positive PET lesion in the mediastinal residual mass, which was interpreted as viable lymphoma. However, histologic examination revealed that it was an eosinophilic granuloma.


Subject(s)
Eosinophilic Granuloma/complications , Eosinophilic Granuloma/diagnosis , Hodgkin Disease/complications , Hodgkin Disease/diagnosis , Tomography, Emission-Computed/methods , Adult , Eosinophils/pathology , Fluorodeoxyglucose F18 , Histiocytosis, Langerhans-Cell/diagnosis , Humans , Islets of Langerhans/cytology , Lymphoma/pathology , Male , Middle Aged , Radiopharmaceuticals , Sensitivity and Specificity , Tomography, X-Ray Computed
16.
Urol Int ; 68(3): 157-63, 2002.
Article in English | MEDLINE | ID: mdl-11919460

ABSTRACT

INTRODUCTION: The role of positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) is currently under evaluation in urologic oncology. The aim of the present study was to investigate the use of [18F]FDG positron emission tomography ([18F]FDG-PET) in the detection and treatment control of malignant germ cell tumors compared to computed tomography (CT). MATERIALS AND METHODS: Thirty-two PET studies and CT scans were carried out in 23 patients with histologically proven germ cell tumors (10 seminomas, 12 non-seminomatous germ cell tumors (NSGCT), 1 unclassified serologic recurrent disease) Lugano stage I-III. The scans were done either after initial diagnosis (n = 21) and/or within 3-45 days after chemotherapy was completed (n = 11). PET and CT were validated either by histology (n = 7) or clinical follow-up of 6-11 months after the last PET study has been performed (n = 16). Sensitivity, specificity, accuracy, positive and negative predictive values were determined for PET and CT. Differences between PET and CT for parameters of diagnostic value were evaluated by chi(2) test. RESULTS: Although not statistically significant, the sensitivity, accuracy and negative predictive value were higher for PET than for CT with respect to the detection of metastatic infradiaphragmatic and supradiaphragmatic lesions after initial diagnosis. The specificity and positive predictive value of PET and CT were comparable. After chemotherapy, PET was found to be significantly superior in specificity and accuracy compared to CT with respect to infradiaphragmatic lesions (p < 0.05). False-positive PET findings in supradiaphragmatic lesions after chemotherapy occurred in the case of inflammatory processes and resulted in a loss of specificity and accuracy compared to CT (p < 0.05). CONCLUSIONS: These preliminary results demonstrate [18F]FDG-PET to be a useful diagnostic tool for the initial staging and treatment control in patients with germ cell tumors. Possible advantages compared to CT, however, are as yet not clearly defined. The possibility of false-positive PET findings due to reactive supradiaphragmatic inflammatory processes early after chemotherapy have to be considered.


Subject(s)
Fluorodeoxyglucose F18 , Germinoma/diagnostic imaging , Radiopharmaceuticals , Testicular Neoplasms/diagnostic imaging , Tomography, Emission-Computed , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin/administration & dosage , Germinoma/drug therapy , Humans , Male , Predictive Value of Tests , Sensitivity and Specificity , Testicular Neoplasms/drug therapy , Tomography, X-Ray Computed
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