Somatostatin receptor imaging in cholangiocarcinoma.
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Bile Duct Neoplasms↗
Biomedical subjects
S Pauwels
Publications and source records attributed to S Pauwels.
Somatostatin receptor: scintigraphy and radionuclide therapy.
Peptide receptor scintigraphy is more sensitive at the biological than anatomical level, in contrast to conventional imaging, which it complements. Neuroendocrine tumours have the most somatostatin receptors in vitro and their metastases are somatostatin receptor positive in vitro, so that [111In-DTPA-D-Phe1]octreotide (OCT) can be used to image them. OCT was compared with conventional imaging techniques (CON) in a European Multicentre Trial. In 350 evaluable patients, CON detected 88%, and OCT 80% (glucagonomas 100%, VIPomas 88%, carcinoids 87%, non-functioning islet cell tumours 82%, insulinomas 46%) of tumour sites but there was no systematic use of abdominal single-photon-emission computerised tomography. OCT demonstrated multiple tumour sites in 62 of 178 patients in whom CON had found only 1 lesion, with 60% confirmed. 12/16 lesions detected by OCT in 11 patients with no lesions according to CON were also confirmed. The impact of OCT on management was evaluated in 235 patients and affected 40%: it determined 29 surgical decisions, led to octreotide therapy in 47, and modified octreotide dose in 18. Six end-stage patients with neuroendocrine tumours were treated with OCT radionuclide therapy (up to a cumulative dose of 53 GBq per patient) in a phase I trial. There were no major side-effects after up to 2 years treatment, with impressive effects on hormone production and a likely anti-proliferative effect.
Humans↗
Indium-111-pentetreotide uptake in endocrine tumors and lymphoma.
UNLABELLED: The biodistribution of 111In-pentetreotide was assessed in patients with gastroenteropancreatic (GEP) neuroendocrine tumors or lymphoma and in control patients and analyzed as a function of scanning time, presence or absence of tumor uptake, tumor type and previous octreotide treatment. METHODS: Patients underwent imaging 4 and 24 hr after injection of approximately 200 MBq 111In-pentetreotide. The frequency of organ visualization was assessed on planar views. Total organ and tumor uptake (% injected dose [ID]) was determined using the geometric mean method and regional tissue uptake (% ID/100 ml) by semiquantitative SPECT. RESULTS: Liver, spleen, kidneys and urinary bladder were visualized in all patients. Thyroid, bowel and pituitary were more often visualized at 24 hr than at 4 hr. Activity in the gallbladder, breast, ureters and ascites was only occasionally observed. Total liver, spleen and thyroid uptake was stable over time, whereas kidney activity decreased slightly. At 24 hr, regional uptake was threefold lower in the liver than in the spleen or kidneys and was similar in the three groups. In patients with long-term octreotide therapy, a positive correlation was found between the duration of octreotide therapy and liver or spleen uptake. Total and regional tumor uptake showed high intraindividual and interindividual variations. Total tumor activity was stable over 24 hr in patients with GEP and decreased in those with lymphoma. The mean regional tumor uptake was 10-fold lower in patients with lymphoma than in those with GEP. Cold octreotide injected 24 hr after tracer administration did not result in any displacement of organ and tumor activity. CONCLUSION: Organ uptake seems not to be influenced by the presence of 111In-pentetreotide-positive lesions or by tumor type. Tumor uptake is highly variable among patients and clearly lower in patients with lymphoma than in those with GEP. The widespread of uptake values in tumors indicates that radiotherapy using radiolabeled somatostatin analogs may not be applicable to all patients with 111In-pentetreotide-positive tumors.
Antineoplastic Agents, Hormonal↗
Reliability of aminopyrine breath test using a single breath collection.
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Aminopyrine↗
Human neutrophil and plasma endopeptidase 24.11: quantification and respective roles in atrial natriuretic peptide hydrolysis.
Neutral endopeptidase 24.11 activities were quantified on human peripheral blood cell preparations (reflecting the enzyme concentration on the surface of neutrophils) and in the corresponding diluted plasmas by a spectrofluorimetric assay. Despite statistically identical values in both compartments, enzymatic activity towards atrial natriuretic peptide was not comparable. Indeed, incubation of the radiolabelled peptide in whole blood resulted in the thiorphan-sensitive production of the labelled metabolites Phe-Arg-Tyr and the Cys-Phe bond-cleaved peptide. A similar degradation pattern was observed for blood cells but not for plasma, providing evidence for the exclusive involvement of neutrophil endopeptidase in this peptide inactivation. In search for plasma component(s) susceptible to inhibit enzymatic activity, we observed that in the presence of alpha 2-macroglobulin at the physiological concentration of 3.5 mg mL-1, endopeptidase activity decreased from 100% to 51.2 +/- 8.9% (P = 0.002). Our data suggest that this protein could play a role in the endogenous inhibition of plasma endopeptidase activity.
Amino Acid Sequence↗
Microsomal function in hepatitis B surface antigen healthy carriers: assessment of cytochrome P450 1A2 activity by the 14C-caffeine breath test.
The hepatitis B surface antigen (HBsAg) carrier state is associated with changes in hepatocellular function involving the cytochrome P450 (CYP) system. Among this system, CYP1A2 enzyme plays an important role in chemical carcinogenesis and in the metabolism of several drugs. We have thus investigated CYP1A2 function using two 14C-caffeine breath tests (3-methyl-14C; C3BT and 7-methyl-14C caffeine; C7BT) in 12 HBsAg healthy carriers and 8 healthy volunteers matched for 14C-aminopyrine breath test values. HBsAg carriers exhibited lower C3- and C7BT values than normal controls. This difference, however, did not reach statistical significance except for C7BT values normalised for aminopyrine breath test values. Our data thus do not support the association between viral presence and CYP1A2 dysfunction.
Adult↗
Somatostatin receptor imaging with indium-111-pentetreotide in gastroenteropancreatic neuroendocrine tumors: safety, efficacy and impact on patient management.
UNLABELLED: Indium-111-pentetreotide, a radiolabeled somatostatin analog, has been proposed for imaging tumors bearing somatostatin receptors. This study evaluates the safety, efficacy and impact on patient management of this scintigraphic agent in patients with gastroenteropancreatic (GEP) neuroendocrine tumors. METHODS: We studied 47 consecutive patients with a proven or clinically suspected GEP neuroendocrine tumor who were imaged 4 and 24 hr after injection of 111In-pentetreotide. The patients were monitored for adverse reactions and changes in vital signs or clinical chemistry over 24 hr. The scintigraphic findings were compared with results from conventional imaging methods. The patients were followed over a minimal 6-mo period during which further localization procedures were performed to confirm or refute the additional tumor sites found at scintigraphy. RESULTS: No adverse reactions or clinically relevant changes in clinical chemistry were noted after injection of the radiopharmaceutical. The final diagnosis of a GEP neuroendocrine tumor was retained in 38 patients. Somatostatin receptor-positive lesions were found in 33 of these patients, whereas conventional methods were positive in 31 patients. Of the 54 sites seen by conventional procedures, 50 sites were also detected scintigraphically. CONCLUSION: Indium-111-pentetreotide is a safe, sensitive imaging agent in the detection of GEP neuroendocrine tumor sites. Indium-111-pentetreotide also provides information on the somatostatin receptor status of the tumor and may therefore aid in therapeutic decisions.
Female↗
Hepatobiliary scintigraphy in a patient with bilhemia.
A 4-year-old child referred for acute jaundice following percutaneous needle biopsy of the liver underwent hepatobiliary scintigraphy. Although all conventional liver tests suggested preservation of hepatocyte function, the tracer uptake in the liver appeared dramatically reduced at scintigraphy and the blood pool activity did not decrease significantly until the end of the study. Visualization of the bile ducts indicated, however, that the tracer was taken up by the hepatocyte and further excreted into the biliary tree. There was no tracer pooling in the biliary tree although no bowel activity was observed, even on delayed images. The association of persistent blood pool activity, bile duct visualization without tracer pooling, and nonvisualization of the bowel was caused by a continuous recirculation of the tracer from the biliary tree into the bloodstream. The presence of a biliovenous fistula was further proven by percutaneous transhepatic cholangiography performed 24 h later. Since 1975, only 16 cases of bilhemia have been reported. To the best of our knowledge the scintigraphic pattern of this rare but life-threatening complication has not previously been reported.
Bile Ducts, Intrahepatic↗
Diagnostic usefulness of radiolabeled pentetreotide scintigraphy and therapeutic efficiency of octreotide in a case of insulinoma.
Although the functional diagnosis of insulinoma is quite easy, its topographic diagnosis still constitutes a major challenge since conventional radiological techniques, e.g. ultrasonography, computed tomography and even selective angiography, fail to recognize the tumor in numbers of insulinomas. We report an observation of a benign insulinoma in an 81-year-old woman that escaped detection by ultrasonography and CT but was later localized by both endoscopic ultrasonography and somatostatin receptor scintigraphy. It illustrates the usefulness of such recent imaging techniques for the localization of islet cell tumors that escaped detection by ultrasonography and CT. Moreover, in our elderly patient who refused surgical intervention, hypoglycemia was corrected by octreotide administration emphasizing the predictive value of 111In-pentetreotide scintigraphy on the subsequent response to octreotide therapy in patients in whom the optimal treatment (surgical resection) is not possible.
Aged↗
Quantitation in SPECT using an effective model of the scattering.
A new method for correcting simultaneously the attenuation, scatter and resolution effects in SPECT has been developed for the case of a homogeneous medium. It is based on an effective model of the scatter process. This model depends on only four parameters which are determined experimentally and remain independent of the geometry and of the dimensions of the scatter medium. The method uses the data from the peak events and does not need additional energy windows on the scattered events. An original filter is proposed to remove the noise due to the poor statistics of clinical data. Tests on phantoms varying in size and activity show that the model allows absolute activity determination with an accuracy of a few per cent.
Algorithms↗
[Semi-quantitative analysis of 3-phase bone scintigraphy data in algodystrophy of the limbs].
Three-phase bone scanning of the extremities (foot or hand) was performed in 40 normal subjects and in 56 patients with an unequivocal clinical diagnosis of reflex sympathetic dystrophy. Ten patients were in the "cold" or atrophic stage of the disease process, whereas 46 were in the "hot" or acute phase. The scintigraphic parameters studied were the ratios of tracer activity in the affected side over the healthy side established for blood flow (BF), blood pool (BP), early vasculo-tissular fixation (EF), and late bone fixation (LF). In the controls, blood flow, blood pool, and early fixation showed considerable interindividual variation and only the variation of late fixation remained within narrow limits. Among the patients, those at the hot stage of the disease had significantly higher values for all four parameters than those at the cold stage. The group at the cold stage did not differ from the controls except for a significantly higher late fixation value. Furthermore, among hot stage patients, 15% to 25% had normal or diminished blood flow, blood pool and early fixation values. At the cold stage of the disease, radionuclide parameters were similar in affected feet and hands, whereas at the hot stage values at the feet were double those at the hands. Finally, statistical analysis revealed that late fixation was most closely correlated with early fixation, which in turn was most close correlated with blood pool. The clinical and pathophysiological significance of these data is discussed.
Adult↗
Localization of gastroenteropancreatic neuroendocrine tumors with 111indium-pentetreotide scintigraphy.
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Diagnostic Imaging↗
Brain tumor imaging with PET and 2-[carbon-11]thymidine.
METHODS: To assess the potential of thymidine for imaging brain tumors, 20 patients with untreated (n = 14) and recurrent (n = 6) supratentorial intracranial tumors were studied with PET by using 2-[11C]thymidine (Tdr), and the results were compared with [18F]fluorodeoxyglucose (FDG) PET data. RESULTS: Blood analysis consistently revealed a rapid clearance of the intact Tdr together with the appearance of CO2/HCO3- that, with time, accounted for approximately 70% of the total blood activity. As soon as 10 min after tracer injection, brain images showed a low and homogeneous Tdr distribution over the normal brain structures (cortex-to-blood ratio approximately 1). Visual and quantitative analysis revealed increased Tdr uptake (tumor-to-cortex ratio > or = 1.2) in 11 of 14 untreated tumors and in 5 of 6 recurrent tumors. No correlation was found between Tdr uptake and tumor grade. In 12 of the 14 untreated tumors, FDG uptake was low (tumor-to-cortex ratio: 0.83 +/- 0.79), but a FDG hot spot was visualized in 8 of 10 high-grade and in none of the 4 low-grade tumors. FDG uptake was consistently low in recurrent tumors (tumor-to-cortex ratio: 0.49 +/- 0.19), and PET-FDG was negative in 3 of the 6 cases. CONCLUSION: These data indicate the feasibility of brain tumor imaging with Tdr and suggest the potential clinical usefulness of the method in the detection of tumor recurrences. The specificity of the method remains, however, to be investigated.
Adolescent↗
Hepatic [14C]aminopyrine demethylation capacity after portocaval shunting. Comparative study in patients with and without arterialization of portal vein.
The [14C]aminopyrine breath test (ABT) was used before and after surgical portocaval shunting in 29 cirrhotic patients, 15 with arterialization of the portal vein and 14 without. These two subgroups were comparable with regard to age, prothrombin time, serum albumin, serum total bilirubin concentrations, Child classification, and preoperative ABT. After portocaval shunt, a striking reduction in ABT values was observed after 6 and 12 months (90.7 +/- 8.0%, P < 0.05 and 77.3 +/- 7.5%, P < 0.005, respectively). No further decrease was observed between 12 and 24 months. The microsomal function was reduced to a greater extent in patients with postnecrotic cirrhosis (55 +/- 4.8%, P < 0.01) than in those with alcoholic cirrhosis (84.8 +/- 10.4%, P < 0.05). Arterialization of the portal stump of the portal vein did not prevent the reduction in hepatocellular function. No significant change in prothrombin time, serum albumin, or bilirubin concentrations was observed during the follow-up period in any of the groups. Overall, preoperative ABT was significantly higher in those surviving one year (0.29 +/- 0.12% administered dose) than in those who died within this time period (0.12 +/- 0.01%, P < 0.005). This observation suggests that portocaval anastomosis induces an early decrease in microsomal function that is not prevented by arterialization of the portal vein. It also suggests that ABT might be helpful in selecting patients for shunt surgery.
Adult↗
Identification of progastrin derived peptides in colorectal carcinoma extracts.
The possible production of gastrin by colorectal carcinomas has been studied. Extracts of 44 tumours and adjacent macroscopically normal tissue were examined in radioimmunoassay using the following antibodies: (i) L289 raised to a C-terminal fragment of progastrin which shows specificity for intact progastrin, but not the extreme C-terminal tryptic peptide; (ii) LW60 raised to a C-terminal fragment of progastrin which reacts with progastrin and its C-terminal tryptic peptide; (iii) 109-21 which was raised to, and reacts with, Gly-extended forms of heptadecapeptide gastrin--that is, biosynthetic intermediates on the pathway producing active gastrin; and (iv) L2 which reacts with amidated, biologically active gastrins. All samples contained detectable material in assays using LW60; in general, concentrations measured with this antibody were higher than with the other antibodies, and in particular there were higher concentrations in tumour compared with normal tissue extracts. Tumour extracts also contained higher concentrations of immunoreactivity compared with normal tissue, in assays using antibodies L289 and 109-21. In contrast, amidated gastrins were found in similar concentrations in tumour and normal tissue, and concentrations were the lowest of those recorded in the four assays. Separation on Sephadex G50 revealed peaks compatible with progastrin and its C-terminal flanking peptide, and two other peaks that are so far unidentified. In conclusion most colorectal carcinomas contain peptides derived from the gastrin precursor, progastrin, but for the most part these tumours do not convert progastrin into biologically active products.
Amino Acid Sequence↗
Noninvasive measurement of liver regeneration with positron emission tomography and [2-11C]thymidine.
The feasibility of liver regeneration determination with [2-11C]thymidine and positron emission tomography was investigated in partially hepatectomized rats. Serial tomographic scans were performed over a 120-minute period after injection of [2-11C]thymidine together with tritium-labeled thymidine. Within 10 minutes after injection, positron emission tomography scans showed a twofold higher hepatic uptake in regenerating than in nonregenerating livers. Time-activity curves over the liver area indicated that the maximal uptake was followed by a faster decrease of 11C radioactivity in controls than in regenerating animals, so that total 11C activity remaining in the liver at 120 minutes accounted for 68% of maximum in regenerating and only 38% in controls. Tissue distribution studies performed at 120 minutes showed that total 11C radioactivity, expressed in percent injected dose per gram, was six times higher in regenerating livers than in controls (0.62% +/- 0.07% in regenerating livers and 0.10% +/- 0.03% in nonregenerating livers; P less than 0.001) and correlated with 3H radioactivity measured in the nuclear fraction (r = 0.92; P less than 0.001). When the hepatic uptake was expressed in percent of dose per organ, the difference between both groups increased (2.31% +/- 0.23% in regenerating livers and 0.29% +/- 0.02% in nonregenerating livers; P less than 0.001) because of higher weight of regenerating livers than of nonregenerating livers (3.83 +/- 0.11 g in regenerating livers and 2.96 +/- 0.16 g in nonregenerating livers; P less than 0.001). In other organs examined, no difference in 11C radioactivity was found between the two groups of rats. These results indicated the potential usefulness of [2-11C]thymidine and positron emission tomography for noninvasive measurement of liver regeneration.
Animals↗
Production of [2-11C]thymidine for quantification of cellular proliferation with PET.
A three-step synthesis of [2-11C]thymidine, using [11C]urea as precursor, is described. [2-11C]Thymine was obtained by cyclization of [11C]urea and diethyl beta-methylmalate in fuming sulfuric acid. After purification of the reaction mixture, [2-11C]thymine and 2'-deoxyribose-1-phosphate were incubated in the presence of thymidine phosphorylase to form [2-11C]thymidine. The whole synthesis procedure, including purification and pharmaceutical package, was achieved within 60 min with a decay corrected yield of 30-35%.
Carbon Radioisotopes↗
Lack of effect by nifedipine on hepatic mixed function oxidase in man.
Nifedipine (NF), a calcium channel blocker, is often prescribed in association with other drugs. Therefore, it was interesting to know whether or not, nifedipine, which is metabolized by the cytochrome P-450NF, was able to induce or to inhibit in vivo the activity of the hepatic mixed function oxidase system. The study was conducted in ten young healthy male volunteers receiving 20 mg NF slow release bid for 15 days. Due to the small number of subjects, comparison of the NF pharmacokinetics at dose 1 and 26 failed to show a bimodality in the frequency distribution of its area under the plasma concentration-time curve (AUC 274.5 to 317.1 ng ml-1 h, NS). Hepatic microsomal autoinduction (t1/2 2.87 to 3.06 h, NS) was not found. No statistically significant effect was seen on the aminopyrine breath test and on the debrisoquine metabolic molar ratio performed before and at the end of the treatment. Unlike what has been suggested by in vitro studies, NF treatment did not modify significantly the urinary excretion of 6 beta-hydroxycortisol (318 to 265 micrograms/d, NS). After the last dose, the total oral clearance of NF was highly correlated with the metabolic clearance to 4-hydroxyantipyrine (r = 0.88; P = 0.005) but the other parameters of antipyrine biotransformation remained unchanged. We conclude that repeated nifedipine oral intake does not modify enzymatic activities of hepatic P-450 cytochromes involved in the biotransformation of antipyrine, aminopyrine, debrisoquine and cortisol.
Adult↗