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W H Knapp

Publications and source records attributed to W H Knapp.

At least 19 recordsLinked to original sources
PubMed2006

Synthesis and preliminary biological evaluation of [123I]Me2Pyr, a new potential ligand for imaging of central cannabinoid CB1 receptors.

A synthesis of 1-(2,4-dichlorophenyl)-5-(4-[123I]iodophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid N',N'-dimethyl-hydrazide ([123I]Me2Pyr), a new radioiodinated analogue of the high-affinity cannabinoid CB1 receptor antagonist SR141716A, is described. Labelling was achieved by radioiododestannylation of the tributylstannyl precursor with [123I]iodide in the presence of chloramine T. HPLC purification afforded the labelled product in 48% radiochemical yield. Preliminary rat brain biodistribution studies with the 125I labelled compound revealed high uptake in the substantia nigra, the globus pallidus externus and the cerebellum, which is consistent with the known distribution of CB1 receptors.

Animals↗
PubMed2004

Pre-operative localisation of hyperfunctional parathyroid tissue with 11C-methionine PET.

PURPOSE: Previous studies have shown high sensitivity of positron emission tomography (PET) with 11C-methionine in the pre-operative localisation of parathyroid adenoma and hyperplasia. Nonetheless, in secondary and tertiary hyperparathyroidism (HPT) and in patients with recurrent disease, pre-operative localisation of adenomatous (PTA) or hyperplastic tissue is still a problem with all available methods. The aim of this study was to define the optimal imaging protocol and to compare the diagnostic value of 11C-methionine PET and 99mTc-methoxyisobutylisonitrile (MIBI) single-photon emission computed tomography (SPECT): in particular, we wished to define the benefit of 11C-methionine in those patients with inconclusive or negative conventional imaging. METHODS: Thirty highly pre-selected patients with HPT were enrolled. Sixteen patients had primary HPT, 12 patients had secondary HPT, and two patients had recurrences of parathyroid carcinomas. All patients had ultrasound of the neck, dual-phase scintigraphy with 99mTc-MIBI and PET with 11C-methionine. SUV(parathyroid)/SUV(cervical soft tissue) (target-to-background) and SUV(parathyroid tissue)/SUV(thyroid tissue) (target-to-non-target) ratios were calculated. After surgery, histology of specimens was obtained in all patients but one. RESULTS: In 12 patients with secondary or tertiary HPT, 36 hyperplastic parathyroid glands were histologically verified. Twenty-five of 36 lesions (69%) were detected with 11C-methionine PET and 17 (47%) with 99mTc-MIBI scintigraphy. PET studies were positive in 17/18 (94%) cases in which HPT was related to adenomas or carcinomas. 99mTc-MIBI scintigraphy/SPECT yielded pathological lesions in 9/18 cases (50%). All eight atypical localisations of parathyroid glands were detected with PET but only six of the eight were detected with 99mTc-MIBI scintigraphy/SPECT. In 10/11 patients with recurrent HPT and non-diagnostic scintigraphy/SPECT, hyperfunctional parathyroid tissue was identified with 11C-methionine PET. The highest SUV(parathyroid)/SUV(cervical soft tissue) ratio was found 10 min, and the highest SUV(parathyroid tissue)/SUV(thyroid tissue) ratio 40 min post injection. In three patients clear delineation of hyperfunctional tissue was only achieved after 40 min post injection. CONCLUSION: 11C-methionine PET is a clinically useful method in highly pre-selected patients with recurrent primary HPT as well as in secondary and tertiary HPT if ultrasound and 99mTc-MIBI SPECT are inconclusive or negative. PET imaging of atypical PTA localisations is more accurate than conventional scintigraphy. In order to achieve optimal contrast of parathyroid glands versus thyroid tissue and adjacent soft tissue, imaging at both 10 min and 40 min is recommended.

Adult↗
PubMed2004

68Ga-labelled DOTA-derivatised peptide ligands.

68Ge/68Ga generators provide cyclotron-independent access to positron emission tomography (PET) radiopharmaceuticals. We describe a system which allows the safe and efficient handling of 68Ge/68Ga generator eluates for labelling of DOTA-derivatised peptide ligands. The system comprises concentration and purification of the 68Ga eluate as well as labelling and purification steps for peptides, and can be used with different 68Ge/68Ga generator types. The suitability and efficiency were tested with two different DOTA-derivatised somatostatin derivatives and a DOTA-derivatised bombesin derivative. Amounts of 10-20 nmol of the peptides were sufficient and resulted in labelling yields of 50% for all peptides. The built-in safety precautions have proven to be appropriate in allowing use of the method for routine clinical applications. The system was set up and operated in a "hot lab" by personnel with no previous experience in the preparation of PET radiopharmaceuticals.

Bombesin↗
PubMed2004

[Positron emission tomography (PET) for diagnosis and monitoring of treatment for urological tumors].

Positron emission tomography (PET) using ((18)F)2-fluoro-D-2-desoxyglucose (FDG) has been shown to be a highly sensitive and specific imaging modality in the diagnosis of primary and recurrent tumors and in the control of therapies in numerous non-urologic cancers. It was the aim of this review to validate the significance of PET as a diagnostic tool in malignant tumors of the urogenital tract. A systematic review of the current literature concerning the role of PET for malignant tumors of the kidney, testicles, prostate, and bladder was carried out. The role of FDG PET for renal cell cancer can be seen in the detection of recurrences after definitive local therapy and metastases. The higher sensitivity of PET in comparison to other therapeutic modalities (CT, ultrasound, MRI) in recurrent and metastatic renal cell cancer suggests a supplemental role of this diagnostic procedure to complement other imaging modalities.The clinical value of PET is established for the identification of vital tumor tissue after chemotherapy of seminomatous germ cell tumors. This diagnostic method has little significance for primary tumor staging and diagnosis of non-seminomatous germ cell tumor because of the high probability of false-negative results in adult teratomas. FDG PET is not sensitive enough in the diagnosis of primary or recurrent tumors in prostate or bladder cancer. Also PET did not prove to be superior to conventional bone scintigram in the detection of mostly osteoblastic metastases in prostate cancer. The recent use of alternative tracers, which are partly not eliminated by urinary secretion (acetate, choline) has increased the sensitivity and specificity of PET also in this tumor entity so that further clinical investigations are needed to validate these technical modifications in their significance for this imaging modality. PET appears to be sufficiently evaluated only for the diagnostic follow-up of patients with seminomatous germ cell tumors after chemotherapy to regard it is the diagnostic tool of first choice. For all other tumors of the urogenital tract this proof is still awaited.

Algorithms↗
PubMed2004

[Guideline for radioimmunotherapy of rituximab relapsed or refractory CD20(+) follicular B-cell non-Hodgkin's lymphoma].

This guideline is a prerequisite for the quality management in the treatment of non-Hodgkin-lymphomas using radioimmunotherapy. It is based on an interdisciplinary consensus and contains background information and definitions as well as specified indications and detailed contraindications of treatment. Essential topics are the requirements for institutions performing the therapy. For instance, presence of an expert for medical physics, intense cooperation with all colleagues committed to treatment of lymphomas, and a certificate of instruction in radiochemical labelling and quality control are required. Furthermore, it is specified which patient data have to be available prior to performance of therapy and how the treatment has to be carried out technically. Here, quality control and documentation of labelling are of greatest importance. After treatment, clinical quality control is mandatory (work-up of therapy data and follow-up of patients). Essential elements of follow-up are specified in detail. The complete treatment inclusive after-care has to be realised in close cooperation with those colleagues (haematology-oncology) who propose, in general, radioimmunotherapy under consideration of the development of the disease.

Antibodies, Monoclonal↗
PubMed2003

Positron emission tomography with 11C-acetate and 18F-FDG in prostate cancer patients.

Visualisation of primary prostate cancer, its relapse and its metastases is a clinically relevant problem despite the availability of state-of-the-art methods such as CT, MRI, transrectal ultrasound and fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET). The aim of this study was to evaluate the efficacy of carbon-11 acetate and (18)F-FDG PET in the detection of prostate cancer and its metastases. Twenty-five patients were investigated during the follow-up of primary prostate cancer, suspected relapse or metastatic disease using (11)C-acetate PET; 15 of these patients were additionally investigated using (18)F-FDG PET. Fourteen patients were receiving anti-androgen treatment at the time of the investigation. Lesions were detected in 20/24 (83%) patients using (11)C-acetate PET and in 10/15 (75%) patients using (18)F-FDG PET. Based on the results of both PET scans, one patient was diagnosed with recurrent lung cancer. Median (18)F-FDG uptake exceeded that of (11)C-acetate in distant metastases (SUV =3.2 vs 2.3). However, in local recurrence and in regional lymph node metastases, (11)C-acetate uptake (median SUVs =2.9 and 3.8, respectively) was higher than that of (18)F-FDG (median SUVs =1.0 and 1.1, respectively). A positive correlation was observed between serum PSA level and both (11)C-acetate uptake and (18)F-FDG uptake. (11)C-acetate seems more useful than (18)F-FDG in the detection of local recurrences and regional lymph node metastases. (18)F-FDG, however, appears to be more accurate in visualising distant metastases. There may be a role for combined (11)C-acetate/(18)F-FDG PET in the follow-up of patients with prostate cancer and persisting or increasing PSA.

Acetates↗
PubMed2003

Functional activity of human sodium/iodide symporter in tumor cell lines.

AIM: The sodium/iodide symporter (NIS) actively transports iodide into thyrocytes. Thus, NIS represents a key protein for diagnosis and radioiodine therapy of differentiated thyroid cancer. Additionally, in the future the NIS gene may be used for cancer gene therapy of non-thyroid-derived malignancies. In this study we evaluated the functionality of NIS with respect to iodide uptake in a panel of tumor cell lines and compared this to gene transfer efficiency. METHODS: A human NIS-containing expression vector and reporter-gene vectors encoding beta-Galactosidase- or EGFP were used for transient transfection of 13 tumor cell lines. Following transfection measurements of NIS-mediated radioiodide uptake using Na(125)I and of transfection efficiency were performed. The latter included beta-Galactosidase activity measurements using a commercial kit and observation by fluorescence microscopy for EGFP expression. RESULTS: In contrast to respective parental cells, most NIS-transfected cell lines displayed high, perchlorate-sensitive radioiodide uptake. Differences in radioiodide uptake between cell lines apparently corresponded to transfection efficiencies, as judged from reporter-gene assays. CONCLUSION: With respect to iodide uptake we provide evidence that NIS is functional in different cellular context. As iodide uptake capacity appears to be well correlated to gene transfer efficiency, cell type-specific actions on NIS (e. g. post-translational modification such as glycosylation) are not inhibitory to NIS function. Our data support the promising role of NIS in cancer gene therapy strategies.

Biological Transport↗
PubMed2003

[[123I]beta-CIT SPECT imaging of dopamine and serotonin transporters in Parkinson's disease and multiple system atrophy.

AIMS: Definition of the regional pattern of dopamine transporter (DAT) dysfunction in advanced Parkinson's disease (PD) and evaluation of a potential correlation between DAT binding and symptoms; elucidation of the role of DAT imaging in the differential diagnosis of PD and multiple system atrophy (MSA); assessment and comparison of serotonin transporter (SERT) binding in PD and MSA. METHODS: [(123)I]beta-CIT SPECT was performed in 14 patients with advanced PD, 10 with moderate MSA and 20 healthy persons. Specific to nonspecific tracer binding ratios (V(3)") were calculated via ROI analysis of uptake images at 4 h (SERT binding) and 24 h (DAT binding) p. i. RESULTS: In PD bilateral reduction of striatal DAT binding (63-70%) was seen. The caudate ipsilateral to the clinically predominantly affected side showed relatively the least impairment. Significant correlations (r = -0.54 to -0.64) between DAT binding and Hoehn and Yahr stage, UPDRS-scores and duration of disease were found. In MSA DAT binding was less reduced (40-48%) targeting the putamen contralateral to the side of clinical predominance. Significantly lower SERT binding was observed in PD midbrain and MSA hypothalamus compared to controls -- and in MSA relative to PD mesial frontal cortex. CONCLUSIONS: In advanced PD striatal DAT binding is markedly reduced with the least reduction in caudate ipsilateral to the clinically predominantly affected side. In moderate MSA with asymmetrical symptoms DAT dysfunction is predominant in the contralateral putamen, a pattern seen in early PD. The reduction of SERT in the midbrain area of PD patients suggests additional tegmental degeneration while in MSA the serotonergic system seems to be more generally affected.

Brain↗
PubMed2002

Establishment of radioactive astatine and iodine uptake in cancer cell lines expressing the human sodium/iodide symporter.

The sodium/iodide symporter (NIS) has been recognized as an attractive target for radioiodine-mediated cancer gene therapy. In this study we investigated the role of human NIS for cellular uptake of the high LET alpha-emitter astatine-211 ((211)At) in comparison with radioiodine as a potential radionuclide for future applications. A mammalian NIS expression vector was constructed and used to generate six stable NIS-expressing cancer cell lines (three derived from thyroid carcinoma, two from colon carcinoma, one from glioblastoma). Compared with the respective control cell lines, steady state radionuclide uptake of NIS-expressing cell lines increased up to 350-fold for iodine-123 ((123)I), 340-fold for technetium-99m pertechnetate ((99m)TcO(4)(-)) and 60-fold for (211)At. Cellular (211)At accumulation was found to be dependent on extracellular Na(+) ions and displayed a similar sensitivity towards sodium perchlorate inhibition as radioiodide and (99m)TcO(4)(-) uptake. Heterologous competition with unlabelled NaI decreased NIS-mediated (211)At uptake to levels of NIS-negative control cells. Following uptake both radioiodide and (211)At were rapidly (apparent t(1/2) 3-15 min) released by the cells as determined by wash-out experiments. Data of scintigraphic tumour imaging in a xenograft nude mice model of transplanted NIS-modified thyroid cells indicated that radionuclide uptake in NIS-expressing tumours was up to 70 times ((123)I), 25 times ((99m)TcO(4)(-)) and 10 times ((211)At) higher than in control tumours or normal tissues except stomach (3-5 times) and thyroid gland (5-10 times). Thirty-four percent and 14% of the administered activity of (123)I and (211)At, respectively, was found in NIS tumours by region of interest analysis ( n=2). Compared with cell culture experiments, the effective half-life in vivo was greatly prolonged (6.5 h for (123)I, 5.2 h for (211)At) and preliminary dosimetric calculations indicate high tumour absorbed doses (3.5 Gy/MBq(tumour) for (131)I and 50.3 Gy/MBq(tumour) for (211)At). In conclusion, NIS-expressing tumour cell lines of different origin displayed specific radionuclide uptake in vitro and in vivo. We provide first direct evidence that the high-energy alpha-emitter (211)At is efficiently transported by NIS. Application of (211)At may direct higher radiation doses to experimental tumours than those calculated for (131)I. Thus, (211)At may represent a promising alternative radionuclide for future NIS-based tumour therapy.

Adenocarcinoma↗
PubMed2002

Influence of rhTSH on [(18)F]fluorodeoxyglucose uptake by differentiated thyroid carcinoma.

The influence of serum TSH levels on fluorine-18 fluorodeoxyglucose (FDG) uptake by recurrences or metastases of differentiated thyroid carcinomas has not yet been clarified. The aim of this study was to ascertain whether the administration of recombinant human thyrotropin (rhTSH) stimulates FDG uptake by such lesions. In this prospective study, 30 patients with positive or equivocal thyroglobulin (Tg) levels and negative or equivocal iodine-131 and/or morphological imaging results (ultrasound, MRI, CT) underwent FDG positron emission tomography (PET) under exogenous TSH suppression and under exogenous TSH stimulation of serum levels by injection of rhTSH. The mean interval between the FDG-PET studies under these two conditions was 9.3+/-8.8 weeks. Serum TSH levels and free thyroid hormones were determined on each occasion. FDG uptake was quantitated using tumour to background ratios (TBRs) and standardised uptake values (SUVs). Under TSH suppression there was focal FDG accumulation in nine subjects (22 tumour-like lesions). The total number of foci was 45. After exogenous TSH stimulation, the number of patients in whom FDG foci were detected was 19, and the number of foci identified was 82 (78 tumour-like lesions). TBR of regions showing positive FDG contrast with either of the modalities averaged 2.54+/-1.89, and under stimulated TSH levels, 5.51+/-2.99 ( P<0.0001). Corresponding SUVs were 2.05+/-1.45 versus 2.77+/-1.58 ( P<0.001). In a small number ( n=4) of foci related to inflammatory lymph nodes, TBR and SUV were only marginally increased under TSH stimulation (2.01+/-0.38 and 1.07+/-0.38, respectively), and the values did not differ significantly from those obtained under suppression. These results provide the first direct evidence that TSH stimulates FDG uptake by differentiated thyroid carcinoma and that, therefore, FDG-PET is more accurate under rhTSH than under suppression.

Adult↗
PubMed2002

The role of cerebral blood flow and cerebrovascular reserve capacity in the diagnosis of chronic hydrocephalus--a PET-study on 60 patients.

AIM: To investigate the clinical value of cerebral blood flow (CBF) and cerebrovascular reserve capacity (CVR) in the management of chronic hydrocephalus. Global cortical CBF and CVR in 60 patients (66 +/- 12 yrs) with chronic hydrocephalus were investigated before, one week (7 d) and 7 months (7 m) after shunting by 15-O-H2O PET (Siemens ECAT 951/31) at rest and after application of acetazolamide (1 g). After 7 months, clinical outcome was assessed according to Stein and Langfitt and patients were classified into responder (n = 31) and non-responder (n = 29). Before Surgery, responder had lower blood flow values compared to non responder (36 +/- 8 vs. 41 +/- 11 ml/100 ml/min; p = 0.04), whereas CVR was not different between outcome groups (33 +/- 10 vs. 41 +/- 8%; p > 0.05). After shunting, CVR in non-responder decreased from 41 +/- 8% to 32 +/- 5% (7 d), whereas in responder significant increases (p < 0.02) to 55 +/- 46% (7 d) and 54 +/- 31% (7 m) were observed. Regarding early individual changes in CVR, the majority (12/18; 66%) of non-responder had marked decreases in CVR-levels (< 30%), whereas clinical responder considerably improved in CVR (> 30%) in half of patients (7/14). Measurement of cerebral blood flow in chronic hydrocephalus might substantially contribute to selection of shunt candidates and neurological sequels may be rather related to early regeneration of the hemodynamic reserve.

Acetazolamide↗
PubMed2002

PET-studies in idiopathic chronic hydrocephalus before and after shunt-treatment: the role of risk factors for cerebrovascular disease (CVD) on cerebral hemodynamics.

AIM: To investigate the impact of cerebrovascular risk factors in idiopathic chronic hydrocephalus concerning cerebral hemodynamics and clinical outcome after shunting. Global cortical cerebral blood flow (CBF) and cerebrovascular reserve capacity (CVR) in 53 patients (67 +/- 11 yrs) were determined by 15-0-water-PET studies before and after administration of acetazolamide (1 g) prior (pre), one week (7 d) and seven months (7 m) after shunting. According to the prevalence of vascular risk factors (American subcommittee on reporting standards for cerebrovascular disease) patients were classified into a "low-risk" (n = 27) and "high-risk" (n = 20) group; patients with a history of stroke (n = 6) were separated. After 7 months, clinical outcome was assessed according to Stein and Langfitt. While CBF in "high-risk" patients prior to surgery was significantly lower in clinical responder compared to non-responder (32 +/- 5 vs. 42 +/- 15 ml/100 ml/min; p < 0.05), CVR was marginal in both outcome groups (< 30%). One week after shunting, CVR in responder of "high-risk" significantly increased (64 +/- 30 vs. 31 +/- 10% pre; p < 0.01). In "low-risk" patients, differences in CVR prior to shunting were found: CVR was lower in clinical responder than in non-responder (36 +/- 11 vs. 47 +/- 22% pre; p > 0.05) and deteriorated in non-responder (29 +/- 15% vs. 47 +/- 22 pre; p < 0.02) one week after shunting. Different peri-operative characteristics in global CVR regarding clinical response after shunting between both "risk-groups" were observed. Pathophysiological mechanisms upon clinical sequels after shunting in idiopathic hydrocephalus may not be unique.

Cerebrospinal Fluid Shunts↗
PubMed2002

Regional cerebral blood flow profiles of shunt-responder in idiopathic chronic hydrocephalus--a 15-O-water PET-study.

AIM: To find out if regional characteristics of cerebral blood flow (CBF) and cerebrovascular reserve capacity (CVR) may indicate shunt response in idiopathic chronic hydrocephalus. 11 patients with idiopathic chronic hydrocephalus (65 +/- 13 yrs) were followed-up within a year after shunting. Patients were classified into clinical responder (n = 5) and non-responder (n = 6) according to Stein and Langfitt. All patients had measurement of CBF and CVR with dynamic 15-O-water PET (Siemens ECAT 951/31) before and after application of acetazolamide (1 g). Regional differences between outcome groups were analysed with "statistical Parametric Mapping" (SPM99b; Wellcome Department, London, UK). Group differences were regarded as significant, when uncorrected p-value on voxel and on cluster level were p < 0.001 and p < 0.05, respectively. Regarding CBF distribution there was significantly reduced CBF in the frontobasal cortex in responder compared to non-responder (cluster level p = 0.026). In CVR, a variety of cortical regions showed significant decreases compared with non-responder: also in frontobasal cortex (on cluster level p = 0.009). However, most significant reductions were found in temporodorsal and limbic cortical regions (on cluster level p < 0.001). Preoperative hemodynamics displayed a regional profile of reduced CBF and CVR in patients with shunt improvement. Prospective studies for determining the accuracy of regional blood flow characteristics for outcome prediction are warranted.

Aged↗
PubMed2002

Neuropsychological sequels to changes in global cerebral blood flow and cerebrovascular reserve capacity after shunt treatment in chronic hydrocephalus--a quantitative PET-study.

AIM: To study relationship of neuropsychological deficits in chronic hydrocephalus before and after shunting with dynamics in cerebral blood flow. In 27 patients (65 +/- 13 yrs) with idiopathic chronic hydrocephalus 11 selected neuropsychological tests, providing a wide range of psychomotor functions, were performed before, one week (early) and 7 months (late) after shunting. Parallel global cortical blood flow (CBF) and cerebrovascular reserve capacity (CVR) were determined by dynamic 15-O-water PET studies (Siemens ECAT 951/31) before and after application of acetazolamide (1 g). Test raw data and changes after treatment were compared with global and regional blood flow values by polynomial regression. No relationship of test profiles with hemodynamics before surgery was found. After one week, improvement of gait was related to an increase in cerebrovascular reserve capacity (p = 0.05). After 7 months changes in mental tests were related to changes in hemodynamics: again increases in CVR were significantly related to improvements in visual attention and verbal memory (p < 0.01). Early improvement of hemodynamic reserve was related to improvement in gait, whereas mental improvement was particularly related to increases in global CVR at later periods after shunting. These results indicate that neurological sequels in idiopathic chronic hydrocephalus after shunting may actually depend on consecutive improvement of cerebral hemodynamics.

Aged↗