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Biomedical subjects

H J Biersack

Publications and source records attributed to H J Biersack.

At least 19 recordsLinked to original sources

Comparison of [18F]FDG-PET and L-3[123I]-iodo-alpha-methyl tyrosine (I-123 IMT)-SPECT in primary lung cancer.

OBJECTIVE: The aim of this study was to evaluate L-3[123I]-iodo-alpha-methyl tyrosine (IMT)-SPECT and FDG-PET in pulmonary lesions suspected to be lung cancer. METHODS: Whole body PET (measured transmission corrected emission scans) was performed 45 minutes after i.v. injection of 222-370 MBq (6-10 mCi) 18F-FDG on a Siemens PET scanner (ECAT EXACT 47) including 5-6 bed positions. 123I-IMT-SPECT (chest) was performed after injection of 370 MBq (10 mCi) with a dual head camera (Picker Prism 2000) and commercially available reconstruction algorithms. Ten patients (6 male and 4 female) with suspected lung cancer were investigated. The results were compared to histological findings after surgery or bronchoscopic biopsies and CT. RESULTS: 123I-IMT-SPECT and FDG-PET were able to detect all 9 cases of lung cancer (1-8 cm in diameter). One case was true negative. Both imaging methods were true positive with respect to mediastinal lymph node metastases in one patient. The tumor/background ratio was higher with PET (8.20 vs. 2.84). CONCLUSION: Despite the limited number of patients it may be concluded that IMT-SPECT as well as FDG-PET are suited to correctly diagnose lung cancer. Nevertheless, FDG-PET, if available, seems to be better suited because of the higher tumor/background ratio and better resolution.

Carcinoma, Non-Small-Cell Lung↗

Value of tumour marker S-100B in melanoma patients: a comparison to 18F-FDG PET and clinical data.

AIM: The S-100B protein is commonly used in the immunohistochemical diagnosis of malignant melanoma and its metastases and has recently been introduced as a tumor marker in peripheral blood, whereas 18F-FDG PET is currently the most sensitive in-vivo imaging method for melanoma staging. Thus, the efficiency of serum S-100B and 18F-FDG PET in the detection of metastatic disease in melanoma patients are compared. METHODS: Serum S-100B was measured with a commercially available immunoradiometric assay. As part of primary tumour staging whole-body positron emission tomography (PET) with 18F labeled fluorodeoxy-D-glucose (18F-FDG) was performed in 67 patients suffering from cutaneous melanoma with a tumour thickness > 0.75 mm and a Clark-level III-V. Final diagnosis based on histology, morphologic imaging results and/or clinical follow-up after at least six months. RESULTS: No evidence of disease was seen in 43 of 67 patients (64.2%), 11 patients (16.4%) presented with lymph node metastases, 13 patients (19.4%) had one or more distant metastases. Alltogether, 18 of 67 patients showed S-100B values > 0.2 microgram/l, including two patients without metastatic disease, 3 of 11 patients with lymph node metastases, and the 13 patients with distant metastases. One patient showed false-positive FDG-uptake in the mediastinum, but presented with S-100B values off curve. CONCLUSION: Our data indicate that serum S-100B determination might be helpful in identifying melanoma patients with distant metastases. In comparison to 18F-FDG PET, the value of serum S-100B for lymph-node staging is limited.

Adult↗

Improved diagnosis of advanced bone marrow metastases by means of radiolabeled antigranulocyte antibodies.

Assessment of bone marrow metastases using Tc-99m-labeled antigranulocyte antibodies and Tc-99m-labeled nanocolloids is discussed in osseous metastasizing breast cancer. A 53-year-old patient with bone metastases of breast cancer (pT2 pN1biv cM1) developed leukocytopenia WHO Grade III following polychemotherapy. Bone marrow scintigraphy with Tc-99m labeled nanocolloids and Tc-99m-labeled antigranulocyte antibodies revealed pronounced bone marrow infiltration as the cause. Comparing both procedures, the images with antigranulocyte antibodies showed a clearly better bone marrow image, considerably higher contrast and almost no superimposition of the liver over the spine. In osseous metastasizing breast cancer, scintigraphy with Tc-99m-labeled antigranulocyte antibodies enables assessment of metastases in the entire bone marrow.

Bone Marrow Neoplasms↗

Posterior cerebral artery Wada test: sodium amytal distribution and functional deficits.

Inadequate sodium amytal delivery to the posterior hippocampus during the intracarotid Wada test has led to development of selective tests. Our purpose was to show the sodium amytal distribution in the posterior cerebral artery (PCA) Wada test and to relate it to functional deficits during the test. We simultaneously injected 80 mg sodium amytal and 14.8 MBq 99mTc-hexamethylpropyleneamine oxime (HMPAO) into the P2-segment of the PCA in 14 patients with temporal lobe epilepsy. To show the skull, we injected 116 MBq 99mTc-HDP intravenously. Sodium amytal distribution was determined by high-resolution single-photon emission computed tomography (SPECT). In all patients, HMPAO was distributed throughout the parahippocampal gyrus and hippocampus; it was also seen in the occipital lobe in all cases and in the thalamus in 11. Eleven patients were awake and cooperative; one was slightly uncooperative due to speech comprehension difficulties and perseveration. All patients showed contralateral hemianopia during the test. Four patients had nominal dysphasia for 1-3 min. None developed motor deficits or had permanent neurological deficits. Neurological deficits due to inactivation of extrahippocampal areas thus do not grossly interfere with neuropsychological testing during the test.

Adult↗

Radiation exposure and radiation protection of the physician in iodine-131 Lipiodol therapy of liver tumours.

Intra-arterial iodine-131 labelled Lipiodol therapy for liver cancer has been investigated for safety and efficacy over a number of years, but data on radiation exposure of personnel have remained unavailable to date. The aim of this study was to assess the radiation exposure of the physician during intra-arterial 131I-Lipiodol therapy for liver malignancies and to develop appropriate radiation protection measures and equipment. During 20 intra-arterial administrations of 131I-Lipiodol (1110-1924 MBq), radiation dose equivalents (RDE) to the whole body, fingers and eyes of the physician were determined for (a) conventional manual administration through a shielded syringe, (b) administration with an automatic injector and (c) administration with a lead container developed in-house. Administration by syringe resulted in a finger RDE of 19.5 mSv, an eye RDE of 130-140 microSv, and a whole-body RDE of 108-119 microSv. The injector reduced the finger RDE to 5 mSv. With both technique (a) and technique (b), contamination of angiography materials was observed. The container allowed safe transport and administration of the radiopharmaceutical from 4 m distance and reduced the finger RDE to <3 microSv and the eye RDE to <1 microSv during injection. During femoral artery compression, radiation exposure to the fingers reached 170 microSv, but the whole-body dose could be reduced from a mean RDE of 114 microSv to 14 microSv. No more contamination occurred. In conclusion, radiation exposure was high when 131I-Lipiodol was administered by syringe or injector, but was significantly reduced with the lead container.

Humans↗

Fluorine-18 fluorodeoxyglucose positron emission tomography findings in spondylodiscitis: preliminary results.

Nuclear medicine procedures can be helpful in diagnosing spine infections. The purpose of the study was to evaluate the findings of positron emission tomography with fluorine-18 fluorodeoxyglucose (FGD-PET) in the detection of spondylodiscitis. We performed FDG-PET in 16 patients with suspected spondylodiscitis. All the patients were operated and underwent histopathological examination. The FDG-PET findings were graded and evaluated by two independent nuclear medicine physicians. Of the 16 patients, 12 had a histopathologically confirmed spondylodiscitis. In all these 12 patients, FDG-PET was true-positive. In the four patients without spondylodiscitis, FDG-PET showed three true-negative and one false-positive result. In spondylodiscitis, the mean standard uptake value (SUV) of FDG was 7.5 (SD+/-3.8). The PET scans depicted the paravertebral soft tissue involvement in cases of spondylodiscitis. Our first results showed that FDG-PET is a very sensitive imaging procedure in the detection of spondylodiscitis. Compared to other nuclear medicine procedures, PET enables a rapid imaging with acceptable radiation dose and high spatial resolution.

Adolescent↗

Case report: regional cerebral hypoperfusion induced by ventricular tachycardia - short-term hippocampal hypoperfusion and its potential relationship to selective neuronal damage.

BACKGROUND: Focussing on regional cerebral hypoperfusion during hemodynamically stable, but borderline hypotensive, sustained ventricular tachycardia (VT) experimental studies show (1) a reduction of cerebral blood flow (CBF) during tachyarrhythmias in contrast to the concept of CBF autoregulation, (2) a mediation of hypoperfusion by neuronal and humoral mechanisms, and (3) an involvment of microcirculation due to an ischemic stress response of the cerebral tissue. The clinical relevance of these observations remains still unclear. CASE REPORTS: Two patients with coronary artery disease, left ventricular dysfunction and sustained monomorphic VT underwent electrophysiological study. VT was induced and the tracer (99m)Tc-HMPAO was injected after 3 minutes of ongoing VT. Regional CBF during this life threatening arrhythmia was determined with brain SPECT. A scanning protocol was performed after termination of VT. The measurements were repeated at baseline during normofrequent sinus rhythm (SR) one week later. CBF during SR was significantly reduced in the temporal lobe in comparison to the conditions during stable VT, particularly in the left hippocampus. CONCLUSION: The reduction of hippocampal CBF due to cerebrovascular vasoconstriction and neuronal reflex mechanism previously observed in experiments during stable, sustained VT can be confirmed in a clinical scenario by high resolution (99m)Tc-HMPAO brain SPECT. This supports the hypothesis that repetitive stable VT can play a role in the pathophysiology of cerebrovascular insufficiency. Further clinical studies are needed to analyze the impact of tachyarrhythmias on cognitive and mnemic function.

Aged↗

Painful multifocal arthritis: therapy with rhenium 186 hydroxyethylidenediphosphonate ((186)Re HEDP) after failed treatment with medication--initial results of a prospective study.

Eight patients (77 joints) with polyarthritis were treated systemically with 570 MBq (15.4 mCi) of rhenium 186 ((186)Re) hydroxyethylidenediphosphonate (HEDP). Pain and disease activity were assessed monthly. In six (75%) of eight patients, a single injection of (186)Re HEDP led to an improvement in disease activity. Systemic low-dose treatment with (186)Re HEDP can reduce pain and disease activity in patients with polyarthritis.

Arthritis, Rheumatoid↗

Inhalation of [123I]alpha1-protease inhibitor: toward a new therapeutic concept of alpha1-protease inhibitor deficiency?

UNLABELLED: The alpha1-protease inhibitor (alpha1-Pi) is separated from human serum and is therefore extremely expensive. Because only 2%-3% concentrates in the lung after intravenous administration, inhalational therapy for alpha1-Pi deficiency would seem likely to be better. The aims of this study were therefore to determine the pattern of deposition of inhaled alpha1-Pi labeled with 123I and measure the amount deposited in the lungs. METHODS: Eighteen patients with congenital severe alpha1-Pi deficiency were enrolled in the study. The low-specific-activity 123I-labeled alpha1-Pi aerosol (median particle size +/- SD, 3.9 +/- 2.5 microm) was generated by an air pressure-driven nebulizer. The patients inhaled for an average of 23.6 +/- 8.9 min. Static scintigrams in two projections were acquired immediately after (T1) and 1 (T2), 4 (T3), and 24 h (T4) after inhalation. The patients were divided into the following three groups according to their forced expiratory volume in 1 s (FEV1): group I, < or =40% of predicted normal (n = 8); group II, 40% < FEV1 < or = 60% of predicted normal (n = 4); group III, >60% of predicted normal (n = 6). RESULTS: The absolute percentage uptake values of alpha1-Pi in group I were 12.4 for T1, 7.3 for T2, 4.6 for T3, and 1.2 for T4; in group II the values were 13.0, 9.6, 6.2, and 2.0, respectively; and in group III, 14.6, 11.4, 6.5, and 3.6, respectively. Differences between the groups were generally statistically significant. Between T1 and T2, the probability value was <0.05 for group I versus group II, <0.006 for group I versus group III, and <0.39 for group II versus group III. Between T1 and T3, the probability value was <0.29 for group I versus group II, <0.22 for group I versus group III, and <0.94 for group II versus group III. Retention (between T1 and T4) was also dependent on the grade of the disease: P < 0.2 for group I versus group II, P < 0.001 for group I versus group III, and P < 0.02 for group II versus group III. Grading of the uptake pattern by three independent experienced investigators (87% agreement) revealed a peripheral deposition that was group dependent. We found that greater peripheral deposition corresponded with lower lung functional impairment: P < 0.5 for group I versus group II, P < 0.01 for group I versus group III, and P < 0.08 for group II versus group III. Degradation also corresponded with functional impairment: P < 0.05 for group I versus group II, P < 0.006 for group I versus group III, and P < 0.3 for group II versus group III. CONCLUSION: The results of this study show that sufficient amounts of alpha1-Pi can be deposited in the periphery of the lung by inhalation at least in patients with low-grade disease. Inhalation of alpha1-Pi may thus represent a new and more convenient route of drug administration.

Administration, Inhalation↗

Immunological consolidation of ovarian carcinoma recurrences with monoclonal anti-idiotype antibody ACA125: immune responses and survival in palliative treatment. See The biology behind: K. A. Foon and M. Bhattacharya-Chatterjee, Are solid tumor anti-idiotype vaccines ready for prime time? Clin. Cancer Res., 7:1112-1115, 2001.

The aim of the present study was to assess whether the induction of specific immune responses by vaccination with the murine monoclonal anti-idiotypic antibody ACA125, which imitates the tumor-associated antigen CA125, has a positive influence on the survival of patients with recurrent ovarian carcinoma. Forty-two patients with platinum-pretreated recurrences were included in a clinical Phase I/II trial of consolidation in third-line therapy. Patients initially received four immunizations with 2 mg of alum-precipitated anti-idiotype ACA125 every 2 weeks and then monthly applications. No serious allergic reactions could be detected within a maximal control period of 56 months. Hyperimmune sera of 27 of 42 patients (64.2%) showed increased concentrations of human antimouse antibodies. Specific anti-anti-idiotypic antibodies as a marker for induced immunity were detected in 28 of 42 patients (66.7%). The survival of the whole ACA125-treated collective of patients after a mean of 12.6 antibody applications was 14.9 +/- 12.9 months. The survival of patients with a positive immune response was 19.9 +/- 13.1 months in contrast with 5.3 +/- 4.3 months in those patients without detectable anti-CA125 immunity (P < 0.0001). According to these results, vaccination with a suitable anti-idiotypic antibody offers an effective way to induce specific immunity against a primarily nonimmunogenic tumor antigen such as CA125 and is associated with a positive impact on the survival of patients with recurrent ovarian cancer with few side effects, which warrants a Phase III trial for ovarian cancer patients after primary therapy.

Antibodies, Anti-Idiotypic↗

Nerve growth factor-mediated expression of galectin-3 in mouse dorsal root ganglion neurons.

Galectin-3, a member of the galectin family of beta-galactoside-specific lectins has been found to be expressed by subsets of dorsal root ganglion (DRG) neurons during development and in adulthood. Here we show that (i) after 3-7 days in vitro, DRG neurons derived from neonatal mice express galectin-3 intra- and extracellularly and (ii) lectin expression requires the presence of nerve growth factor (NGF). After 3 days in vitro, a higher number of DRG neurons expressed galectin-3 in the presence of NGF (65 +/- 7%) than in the presence of brain-derived neurotrophic factor (BDNF, 30 +/- 3%) or neurotrophin-3 (NT-3, 34 +/- 3%). After 7 days in vitro, these numbers dropped to 51 +/- 3% (for NGF), 0% (for BDNF) and 8 +/- 4% (for NT-3), respectively. Our findings provide first evidence for the contribution of a neurotrophin to the neuronal expression of galectins and suggest an NGF/TrkA-mediated expression of galectin-3 by early postnatal DRG neurons.

Animals↗

SATSCOM--Selective amobarbital test intraarterial SPECT coregistered to MRI: description of a method assessing selective perfusion.

For evaluation of potential functional deficits, an intraarterial amobarbital test is performed prior to neurosurgical or neuroradiological interventions. To visualize individual amobarbital perfusion patterns, simultaneous injection of (99m)Tc-HMPAO was performed previously. The present study describes for the first time a method of coregistration of intraarterial SPECT during selective amobarbital test to MRI. Three patients undergoing selective amobarbital test of the posterior cerebral artery were included. SATSCOM (Selective amobarbital test intraarterial SPECT coregistered to MRI) was performed by skull extraction in SPECT and MRI followed by surface matching. In all three patients, SATSCOM revealed accurate matching results. With this functional-anatomical mapping, suppression of higher cortical functions can be correlated to anatomical regions. Furthermore, a more precise mapping of amobarbital effect improves planning invasive interventions, particularly those close to eloquent areas.

Adult↗

[Diagnostic value of pentavalent 99mTc-dimercaptosuccinicacid ([V]-DMSA) in head and neck tumors].

The purpose of this investigation was to assess the biodistribution of 99mTc-[V]-DMSA in human being, and its diagnostic value in patients with head and neck tumours. 20 patients with histologically confirmed head and neck tumours were examined with planar as well as SPECT scintigraphy. Whole body scintigraphy in different time after injection of 99mTc-[V]-DMSA was performed to assess the major sequential organ biodistribution. Our results showed that the blood clearance of 99mTc-[V]-DMSA was bi-exponential. All organs except kidneys showed a relatively rapid elimination of 99mTc-[V]-DMSA. The kidneys showed a increasing accumulation in the first 2 h, which is probably due to the tubular reabsorption of 99mTc-[V]-DMSA. In 15 of 20 patients, 19 lesions could be proven by means of planar scintigraphy (corresponding sensitivity of 75%). 29 lesions in 18 patients could however be detected by the application of SPECT (corresponding sensitivity of 90%). Except primary tumours and local lymphadenmetastases in 5 patients distant metastases (3 thorax wall, 1 liver and 1 inguinal/paravesicle) were found. Altogether a sensitivity of 76.9% and a specificity of 71.4% were calculated for the detection of primary tumour. The sensitivity and specificity for the exploration of lymphadenmetastases were 75% and 100%. In conclusion, this study show that 99m Tc-[V]-DMSA, particularly with SPECT imaging, is useful in localising the primary tumours and lymphadenmetastases as well as distant metastases of head and neck tumours. The possible therapeutic application of 188/186Re-[V]-DMSA is also evaluated.

Adult↗

Dose escalation study with rhenium-188 hydroxyethylidene diphosphonate in prostate cancer patients with osseous metastases.

The aim of this study was to determine the maximum tolerated dose of rhenium-188 hydroxyethylidene diphosphonate (HEDP) in prostate cancer patients with osseous metastases who are suffering from bone pain. Twenty-two patients received a single injection of escalating doses of carrier-added 188Re-HEDP [1.3 GBq (35 mCi), 2.6 GBq (70 mCi), 3.3 GBq (90 mCi) and 4.4 GBq (120 mCi)]. Blood counts and biochemical parameters were measured weekly over a period of 8 weeks. Haematological toxicity (WHO grading) of grade 3 or 4 was considered unacceptable. Clinical follow-up studies including methods of pain documentation (medication, pain diary) were performed for 6 months after treatment. In the 1.3-GBq group, no haematological toxicity was observed. First haematotoxic results were noted in those patients with a dose of 2.6 GBq 188Re-HEDP. In the 3.3-GBq group, one patient showed a reversible thrombopenia of grade 1, one a reversible thrombopenia of grade 2 and three a reversible leukopenia of grade 1. In the 4.4-GBq group, thrombopenia of grades 3 and 4 was observed in one and two patients (baseline thrombocyte count <200x10(9)/l), respectively, and leukopenia of grade 3 was documented in one patient. The overall nadir of thrombopenia was at week 4. The individual, maximum percentage decrease in thrombocytes in the 1.3-, 2.6-, 3.3- and 4.4-GBq groups was 17%, 40%, 60% and 86%, respectively. In two patients, a transient increase in serum creatinine was observed (max. 1.6 mg/dl). Pain palliation was reported by 64% of patients, with a mean duration of 7.5 weeks. The response rate seemed to increase with higher doses, reaching 75% in the 4.4-GBq group. It is concluded that in prostate cancer patients, the maximum tolerated dose of 188Re-HEDP is 3.3 GBq if the baseline thrombocyte count is below 200x10(9)/l. In patients with thrombocyte counts significantly above 200x10(9)/l, a dose of 4.4 GBq might be tolerable. Thrombo- and leukopenia are the most important side-effects. Pain palliation can be achieved in 60%-75% of patients receiving a dose of 2.6 GBq or more of 188Re-HEDP. Studies in a larger patient population are warranted to evaluate further the palliative effect of 188Re-HEDP.

Bone Neoplasms↗

Testicular function after radioiodine therapy for thyroid carcinoma.

Radiotherapy can cause infertility in both men and women. However, few data are available concerning the effects of radioiodine therapy for thyroid carcinoma on testicular function. We investigated 25 men (age 23-73 years) with differentiated thyroid carcinoma in a longitudinal prospective trial. Follicle-stimulating hormone (FSH), inhibin B, luteinising hormone (LH) and testosterone were measured before (n = 25) and 3 months (n = 11), 6 months (n = 18), 12 months (n = 22), and 18 months (n = 18) after radioiodine therapy [radioiodine dose (mean +/- SEM): 9.8+/-0.89 GBq]. Before therapy, FSH was 5.4+/-0.77 IU/l; it increased significantly (P<0.001) to 21.3+/-2.4 IU/l after 6 months and fell to 7.4+/-1.3 IU/l after 18 months (normal range: 1.8-9.2 IU/l). Inhibin B was significantly decreased (P<0.001) from 178+/-25.3 pg/ml before therapy to 22.2+/-5.5 pg/ml after 3 and 29.4+/-5.7 pg/ml after 6 months and rose to 154+/-23.3 pg/ml after 18 months (normal range 75-350 pg/ml). LH and testosterone were within the normal range during the whole study (1.6-9.2 IU/l and 10.4-34.7 nmol/l, respectively). LH was significantly increased (P<0.001) from 2.8+/-0.33 IU/l before therapy to 5.9+/-0.69 IU/l 6 months after therapy and then fell slowly to 4.0+/-0.45 IU/l after 18 months. Total testosterone was significantly increased (P<0.01) from 12.8+/-0.99 nmol/l at baseline to 19.8+/-1.7 nmol/l after 12 months and 19.6+/-1.7 nmol/l after 18 months. The testosterone/LH ratio (normal range: 3.3-17.9 nmol/IU) fell from 5.8+/-0.66 nmol/IU to 3.0+/-0.36 nmol/IU after 3 months (P<0.01); it remained close to the latter value after 6 months (3.4+/-0.49 nmol/IU) and then rose to 5.5+/-0.6 nmol/IU after 18 months. In conclusion, 3 and 6 months after radioiodine therapy all patients showed elevated FSH and decreased inhibin B levels, reflecting severely impaired spermatogenesis. At the same time a compensated insufficiency of the Leydig cell function was observed. Eighteen months after the last radioiodine therapy, mean values of gonadal function had completely recovered.

Adult↗