PubMed Health⌕ Search

Biomedical subjects

E P Krenning

Publications and source records attributed to E P Krenning.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of [(177)Lu-DOTA(0),Tyr(3)]octreotate and [(177)Lu-DOTA(0),Tyr(3)]octreotide: which peptide is preferable for PRRT?

PURPOSE: Patients with somatostatin receptor subtype 2-positive metastasised neuroendocrine tumours can be treated with [(177)Lu-DOTA(0),Tyr(3)]octreotate. Some use octreotide as the peptide for peptide receptor radionuclide therapy (PRRT). We compared in seven patients [(177)Lu-DOTA(0),Tyr(3)]octreotide ((177)Lu-DOTATOC) and [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-DOTATATE), to see which peptide should be preferred for PRRT with (177)Lu. METHODS: In the same patients, 3,700 MBq (177)Lu-DOTATOC and 3,700 MBq (177)Lu-DOTATATE was administered in separate therapy sessions. Amino acids were co-administered. Whole-body scanning was performed on days 1, 4 and 7 post therapy. Blood and urine samples were collected. We calculated residence times for tumours, spleen and kidneys. RESULTS: All patients had longer residence times in spleen, kidneys and tumours after use of (177)Lu-DOTATATE (p=0.016 in each case). Comparing (177)Lu-DOTATATE with (177)Lu-DOTATOC, the mean residence time ratio was 2.1 for tumour, 1.5 for spleen and 1.4 for kidneys. Dose-limiting factors for PRRT are bone marrow and/or kidney dose. Although the residence time for kidneys was longer when using (177)Lu-DOTATATE, the mean administered dose to tumours would still be advantageous by a factor of 1.5, assuming a fixed maximum kidney dose is reached. Plasma radioactivity after (177)Lu-DOTATATE was comparable to that after (177)Lu-DOTATOC. Urinary excretion of radioactivity was comparable during the first 6 h; thereafter there was a significant advantage for (177)Lu-DOTATOC. CONCLUSION: (177)Lu-DOTATATE had a longer tumour residence time than (177)Lu-DOTATOC. Despite a longer residence time in kidneys after (177)Lu-DOTATATE, tumour dose will always be higher. Therefore, we conclude that the better peptide for PRRT is octreotate.

Adult↗
PubMed2006

In vivo radionuclide uptake quantification using a multi-pinhole SPECT system to predict renal function in small animals.

PURPOSE: In vivo quantification of radiopharmaceuticals has great potential as a tool in developing new drugs. We investigated the accuracy of in vivo quantification with multi-pinhole single-photon emission computed tomography (SPECT) in rats. METHODS: Fifteen male Lewis rats with different stages of renal dysfunction were injected with 50 MBq 99mTc-dimercaptosuccinic acid. Four to six hours after injection, SPECT of the kidneys was acquired with a new four-headed multi-pinhole collimator camera. Immediately after imaging the rats were sacrificed and the kidneys were counted in a gamma-counter to determine the absorbed activity. SPECT data were reconstructed iteratively and regions of interest (ROIs) were drawn manually. The absolute activity in the ROIs was determined. RESULTS: Uptake values ranging from 0.71% to 21.87% of the injected activity were measured. A very strong linear correlation was found between the determined activity in vivo and ex vivo (r2=0.946; slope m=1.059). CONCLUSION: Quantification in vivo using this multi-pinhole SPECT system is highly accurate.

Animals↗
PubMed2006

Practical aspects of peptide receptor radionuclide therapy with [177Lu][DOTA0, Tyr3]octreotate.

Lutetium-177 is increasingly used in patients for receptor-targeted radionuclide therapy with peptides such as [DOTA0,Tyr3]octreotate. In our therapy facility, we are performing yearly 400 treatments with each 7.4 GBq [177Lu][DOTA0,Tyr3]octreotate. Finger dosimetry data during radiolabeling reveal higher doses on the right hands of right-handed workers with the highest equivalent dose for the middle finger (53+/-12 microSv/GBq). Extrapolating dosimetry data, assuming 400 doses of 7.4 GBq per year performed by 4 workers, result in a mean equivalent dose of 23+/-11 mSv and 14+/-6 mSv for finger top and ring dose, respectively. Preparation of 400 doses will result in an effective dose of 0.5-1.5 mSv per year for these 4 workers. The extra radiation dose for workers during the radiolabeling of these doses thus remains below 10% of the legal annual limits, which is in accordance with the ALARA optimization principle. Based on measurements of the maximal radiation level at 1 m distance (7.5+/-3.6 microSv/h), patients treated with 7.4 GBq [177Lu][DOTA0,Tyr3]octreotate can already leave the therapy facility the next day. As radioactive waste streams are based on the half-lives of the used radionuclides, 177Lu-waste (t1/2=6.7 d) was initially collected along with the 131I-waste (t1/2=8 d). According to both manufacturers' specifications, 177Lu contains less than 0.4 kBq 177mLu/MBq 177Lu (at the end of neutron irradiation), when produced by the [176Lu n, gamma 177Lu] reaction via thermal neutron bombardment of enriched lutetium oxide. Unfortunately, because of the huge amounts of 177Lu used, contaminating 177mLu turned out to prevent the quick discharge of this waste, for some containers even after some years of storage. Therefore, a technique for calibrating 177mLu was developed, simultaneously confirming the manufacturer's specifications on the presence of 177mLu in 177Lu. Subsequently a reliable technique was developed to measure 177mLu in waste containers using a beta/gamma-contamination monitor. It is advised to collect 177mLu/177Lu-waste and certainly high-activity lutetium waste separated from 131I according the regulations in the country of use. Apart from the mentioned waste, excreta from patients are collected in decay tanks, where they are stored for 1-2 months before they are discarded into the general sewer within the overall tolerated discharge limit (150 radiotoxicity equivalents/year for our department).

Body Burden↗
PubMed2005

The effect of etanercept on Graves' ophthalmopathy: a pilot study.

PURPOSE: To assess the effect of etanercept, an antitumour necrosis factor (anti-TNF) drug, on clinical signs in Graves' ophthalmopathy (GO). METHODS: A total of 10 consecutive patients (seven female, three male) with recent-onset, active, mildly-to-moderately severe GO were treated with subcutaneous injections of 25 mg etanercept (Enbrel) twice weekly during 12 weeks. The average age was 50 years (range: 39-59 years). The average duration of GO was 4 months (range: 2-6 months). All patients were at least 2 months euthyroid with medication. The mean pretreatment clinical activity score (CAS) was 4 (range: 3-6). RESULTS: The mean CAS prior to treatment was 4, at 6 weeks 2.6, and at 12 weeks 1.6. The mean ophthalmopathy index (OI) prior to treatment was 5.8, at 6 weeks 4.8, and at 12 weeks 4.4. Thus, after 12 weeks of treatment the mean CAS had decreased by 2.4+/-1.3 (60%), and the mean OI had decreased by 1.4+/-1.2 (24%). The main decrease of the CAS and OI was noted at 6 weeks of treatment. The difference was particularly evident on soft-tissue changes, including periocular chemosis and redness. The mean exophthalmometry values did not change. In all, 60% percent of patients reported moderate to marked improvement. In three patients, the GO flared up again after cessation of treatment. There were no serious adverse events or side effects during a mean follow-up time of 18 months. CONCLUSIONS: This study strongly suggests that etanercept may suppress the clinical signs in GO, but randomized controlled trials are needed to further evaluate the effect of anti-TNF treatment and to compare its side-effects with those of corticosteroids.

Adult↗
PubMed2005

Neuroendocrine tumors and somatostatin: imaging techniques.

Tumors and metastases bearing the somatostatin receptor subtypes 2 (SSTR2) or SSTR5 can be visualized in vivo after injection of radiolabeled octapeptide somatostatin analogs like 111In-pentetreotide. The sensitivity of 111In-pentetreotide scintigraphy for the detection of carcinoid tumors is 86-95%. The sensitivity of 111In-pentetreotide scintigraphy for the detection of gastrinomas, vasoactive intestinal polypeptide-secreting tumors, and glucagonomas as well as clinically non-functioning lesions is 75-100%. However, for insulinoma this is 50-60%. 111In-pentetreotide scintigraphy generally has a lower detection rate for benign pheochromocytomas than 123I-MIBG scintigraphy, but it can have a complementary role for the staging of malignant pheochromocytomas. It can also be used for the detection of extra-adrenal pheochromocytomas and paragangliomas. Most GH- and TSH-secreting pituitary adenomas can be visualized using 111In-pentetreotide. 111In-pentetreotide scintigraphy is negative in microprolactinomas and ACTH-secreting pituitary microadenomas. 111In-pentetreotide scintigraphy has been successful for the localization of extra-pituitary ACTH-secreting tumors and their metastases, and especially for occult tumors. A large variety of lesions in and around the pituitary region express somatostatin receptors and, therefore, can be visualized by 111In-pentetreotide scintigraphy.

Carcinoid Tumor↗
PubMed2005

Molecular radiotherapy with somatostatin analogs for (neuro-)endocrine tumors.

Peptide receptor radionuclide therapy (PRRT) holds great promise for the future regarding the treatment of various cancers. With the use of radiolabelled peptides, which bind with high affinity to their receptors on cancer cells, it is possible to target the cancer efficiently. In gastroenteropancreatic tumors, radiolabelled somatostatin analog therapy has proven to be effective. Dose-limiting organs are the bone marrow and the kidneys. With the currently used dose schemes and kidney protection, PRRT is relatively safe and serious side-effecs are rare. Which radiolabelled somatostatin analog can be regarded as the most effective therapy cannot be concluded from the available literature. Also, the development of therapy strategies with combinations of different radionuclides and or peptides is of interest as these strategies may provide an increase in therapeutic efficacy in the future.

Humans↗
PubMed2004

Estrogen receptor alpha gene polymorphisms and bone mineral density in healthy children and young adults.

The accretion of peak bone mass is largely under genetic control, and one of the potential candidate genes is the estrogen receptor alpha (ERalpha) gene. The association of ERalpha gene polymorphisms with bone mineral density (BMD) was investigated in a group of 147 healthy caucasian children, adolescents, and young adults (57 boys and 90 girls) in a cross-sectional and longitudinal study. The mean age was 11.3 years (4.3-19.9 years) at baseline and 15.6 years (7.6-25.3 years) at follow-up. Lumbar spine, total body BMD, and body composition were measured by dual energy X-ray absorptiometry and expressed as age- and sex-adjusted standard deviation scores (SDS). We analyzed two restriction fragment length polymorphisms, Pvull and Xbal, and haplotypes thereof. Subjects homozygous for haplotype 1 (px) (33% of the population) had 0.4 SD (standard deviation) lower lumbar spine BMD (P = 0.02) and bone mineral apparent density (BMAD) (P = 0.04) than those heterozygous or noncarriers for haplotype 1 (px) at baseline. Analysis of the follow-up data gave similar results. The association was stronger for the prepubertal than for the postpubertal subjects. Vertebral width SDS, total body BMD SDS, height SDS, body mass index SDS, lean body mass SDS, and percentage fat SDS did not significantly differ between the haplotypes. The age of menarche was not related to any of the haplotypes in girls. The present study shows that Pvull-Xbal ERalpha gene polymorphism is associated with BMD during childhood.

Absorptiometry, Photon↗
PubMed2004

Thyroxine plus low-dose, slow-release triiodothyronine replacement in hypothyroidism: proof of principle.

Studies in hypothyroid rats show that, when infused with a combination of thyroxine (T4) plus triiodothyronine (T3) to normalize thyrotropin (TSH), euthyroidism in all organs is only ensured when T(4) and T(3) are administered in a ratio as normally secreted by the rat thyroid. As substitution with T(4)-only results in an abnormal serum T(4)/T(3) ratio, it is also possible that in humans, euthyroidism does not exist at the tissue level in many organs, considering that iodothyronine metabolism in the human and the rat share many similar mechanisms. Recent reports in which cognitive function and well-being are compared in patients with primary hypothyroidism substituted with T(4)-only versus substitution with T(4) plus T(3) result in controversial findings in that either positive or no effects were found. In all these studies T(3) was used in the plain form that results in nonphysiologic serum T(3) peaks. In these studies it is suggested that substitution with T(3 )should preferably be performed with a preparation that slowly releases T(3) to avoid these peaks. In the study reported here we show that treatment of hypothyroid subjects with a combination of T(4) plus slow-release T(3) leads to a considerable improvement of serum T(4) and T(3) values, the T(4)/T(3) ratio and serum TSH as compared to treatment with T(4)- only. Serum T(3) administration with slow-release T(3) did not show serum peaks, in contrast to plain T(3).

Area Under Curve↗
PubMed2004

Considerations concerning a tailored, individualized therapeutic management of patients with (neuro)endocrine tumours of the gastrointestinal tract and pancreas.

Endocrine tumours of the gastrointestinal tract and pancreas may present at different disease stages with either hormonal or hormone-related symptoms/syndromes, or without hormonal symptoms. They may occur either sporadically or as part of hereditary syndromes. In the therapeutic approach to a patient with these tumours, excessive hormonal secretion and/or its effects should always be controlled first. Tumour-related deficiencies or disorders should also be corrected. Subsequently, control should be aimed at the tumour growth. Surgery is generally considered as first-line therapy for patients with localized disease, as it can be curative. However, in patients with metastatic disease the role of first-line surgery is not clearly established and other therapies should be considered, such as non-surgical cytoreductive therapies, biotherapy (with somatostatin analogues or interferon-alpha), embolization and chemoembolization of liver metastases, chemotherapy (with single or multiple dose regimens) and peptide receptor-targeted radiotherapy. The delicate balance of the use of the different therapeutical options in patients with endocrine tumours of the gastrointestinal tract and pancreas emphasizes the importance of team approach and team expertise.

Gastrinoma↗
PubMed2003

Vitamin D receptor gene polymorphism predicts height and bone size, rather than bone density in children and young adults.

Peak bone mass is considered to be under strong genetic control. We studied the association among anthropometry, bone density and vitamin D receptor (VDR) genotype in an ethnically homogeneous group of 148 Caucasian children and young adults. Bone density was measured by dual energy X-ray absorptiometry (DXA) and VDR genotype was determined by a direct haplotyping procedure of the BsmI, ApaI, and TaqI restriction fragment length polymorphisms. A second DXA measurement was made after approximately 4 years. Results are expressed as age- and sex-adjusted standard deviation scores (SDS). Previously, the collagen IA1 Sp1 polymorphism was studied in this population. We found VDR genotype to be associated with a 0.4 SDS increased height per allele copy of haplotype '3' (P = 0.04) and a 0.4 SDS increased width of the lumbar vertebral body in the haplotype '3' allele carriers (P = 0.05). We observed a trend towards a 0.3 SDS decreased bone mineral apparent density of lumbar spine (BMAD) per copy of haplotype '3' allele (P = 0.10). In contrast, no association with areal bone mineral density (BMD) was observed. In the follow-up analyses, no differences in height or bone gain among the VDR genotypes were demonstrated. By combining the risk alleles of VDR and collagen IA1 Sp1 genotype, an additive genotype effect on height (P = 0.006) and vertebral body width (P = 0.001) was found. In this exploratory study we found VDR genotype to be associated with frame size and BMAD. The VDR genotype effects on stature and bone size seem to neutralize the effect on areal BMD.

Absorptiometry, Photon↗
PubMed2003

Stabilised 111In-labelled DTPA- and DOTA-conjugated neurotensin analogues for imaging and therapy of exocrine pancreatic cancer.

Neurotensin (NT) receptors are overexpressed in exocrine pancreatic cancer and Ewing's sarcoma. The potential utility of native NT in cancer diagnosis and therapy is, however, limited by its rapid degradation in vivo. Therefore, NT analogues were synthesised with modified lysine and arginine derivatives to enhance stability and coupled either to DTPA, to enable high specific activity labelling with indium-111 for imaging, or to DOTA, to enable high specific activity labelling with beta-emitting radionuclides, such as lutetium-177 and yttrium-90. Based on serum stability (4 h incubation at 37 degrees C in human serum) and receptor binding affinity, the five most promising analogues were selected and further evaluated in in vitro internalisation studies in human colorectal adenocarcinoma HT29 cells, which overexpress NT receptors. All five NT analogues bound with high affinity to NT receptors on human exocrine pancreatic tumour sections. The analogues could be labelled with (111)In to a high specific activity. The (111)In-labelled compounds were found to be very stable in serum. Incubation of HT29 cells with the (111)In-labelled analogues at 37 degrees C showed rapid receptor-mediated uptake and internalisation. The most promising analogue, peptide 2530 [DTPA-(Pip)Gly-Pro-(PipAm)Gly-Arg-Pro-Tyr-tBuGly-Leu-OH] was further tested in vivo in a biodistribution study using HT29 tumour-bearing nude mice. The results of this study showed low percentages of injected dose per gram tissue of this (111)In-labelled 2530 analogue in receptor-negative organs like blood, spleen, pancreas, liver, muscle and femur. Good uptake was found in the receptor-positive HT29 tumour and high uptake was present in the kidneys. Co-injection of excess unlabelled NT significantly reduced tumour uptake, showing that tumour uptake is a receptor-mediated process. With their enhanced stability, maintained high receptor affinity and rapid receptor-mediated internalisation, the (111)In-labelled DTPA- and DOTA-conjugated NT analogues are excellent candidates for imaging and therapy of exocrine pancreatic cancer, peptide 2530 being the most promising analogue.

Animals↗
PubMed2003

Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA(0),Tyr3]octreotate.

Medical treatment and chemotherapy are seldom successful in achieving objective tumour reduction in patients with metastatic neuroendocrine tumours. Treatment with the radiolabelled somatostatin analogue [(90)Y-DOTA(0),Tyr(3)]octreotide may result in partial remissions in 10-25% of patients. The newer analogue [DOTA(0),Tyr(3)]octreotate (octreotate) has a ninefold higher affinity for the somatostatin receptor subtype 2 as compared with [DOTA(0),Tyr(3)]octreotide. Also, labelled with the beta- and gamma-emitting radionuclide (177)Lu, it has proved very successful in achieving tumour regression in animal models. The effects of (177)Lu-octreotate therapy were studied in 35 patients with neuroendocrine gastro-entero-pancreatic (GEP) tumours who underwent follow-up for 3-6 months after receiving their final dose. Patients were treated with doses of 100, 150 or 200 mCi (177)Lu-octreotate, to a final cumulative dose of 600-800 mCi, with treatment intervals of 6-9 weeks. Nausea and vomiting within the first 24 h after administration were present in 30% and 14% of the administrations, respectively. WHO toxicity grade 3 anaemia, leucocytopenia and thrombocytopenia occurred after 0%, 1% and 1% of the administrations, respectively. Serum creatinine and creatinine clearance did not change significantly. The effects of the therapy on tumour size were evaluable in 34 patients. Three months after the final administration, complete remission was found in one patient (3%), partial remission in 12 (35%), stable disease in 14 (41%) and progressive disease in seven (21%), including three patients who died during the treatment period. Tumour response was positively correlated with a high uptake on the octreoscan, limited hepatic tumour mass and a high Karnofsky Performance Score. Because of the limited efficacy of alternative therapies, many physicians currently adopt an expectant attitude when dealing with patients with metastatic GEP tumours. However, in view of the high success rate of therapy with (177)Lu-octreotate and the absence of serious side-effects, we advocate its use in patients with GEP tumours without waiting for tumour progression.

Abdominal Pain↗
PubMed2003

The role of octreotide scintigraphy in rheumatoid arthritis and sarcoidosis.

Somatostatin receptors are widely expressed on cells and tissues throughout the human body. Apart from their expression in the physiological target organs of the peptide, somatostatin receptors are also expressed in various tumours. The expression of somatostatin receptors on neuroendocrine tumours led to the development of somatostatin receptor scintigraphy using [(111)In-DTPA-D-Phe(1)]-octreotide ((111)In-pentetreotide) in order to visualize somatostatin receptor positive tumours and their metastases in vivo. Previous studies reported the expression of somatostatin receptors in both normal and pathological cells and tissues of the human immune system as well. Somatostatin receptors have been demonstrated in Hodgkin's and non-Hodgkin's lymphomas and sst scintigraphy has shown to be a useful tool in diagnosis and staging of these diseases. Moreover, sst expression has also been detected in granulomateus diseases, like sarcoidosis and auto-immune diseases, like rheumatoid arthritis. In this paper we discuss the (possible) role of somatostatin receptor scintigraphy in diagnosis, staging or follow-up of patients suffering from sarcoidosis and rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed2002

Collagen Ialpha1 polymorphism is associated with bone characteristics in Caucasian children and young adults.

A large proportion of the variation in bone mass can be explained by genetic factors. We analyzed the G to T substitution in the Sp1 binding site in the first intron of the collagen type Ialpha1 (COLIA1) gene in relation to bone mass. The genotypes GG, GT, and TT were determined in 148 Caucasian children and young adults. We performed dual energy X-ray absorptiometry twice (mean follow-up time 4.4 years), and speed of sound (SOS) was assessed by tibial ultrasonometry at follow-up. Genotype distribution was 104 (70%) GG, 40 (27%) GT and 4 (3%) TT. Carriers of the T-allele had a 0.5 SDS (standard deviation score) decreased bone mineral content (BMC) of total body (P = 0.001), and a 0.4 SDS decreased bone mineral density (BMD) for both lumbar spine (P = 0.04) and total body (P = 0.05). The genotype effect on BMD and BMC decreased after adjustment for height or body mass index. When we calculated apparent BMD, these differences diminished to 0.1 SDS and were no longer significant. T-allele carriers had shorter stature (0.4 SDS; P = 0.04) and smaller bones (0.5 SDS lower width of the lumbar vertebral body; P = 0.01). The T-allele was also associated with lower SOS (P = 0.03), independent of BMD and BMC, and lower lean body mass. Similar associations were found at follow-up. The change in BMD and BMC SDS between the first and second measurement did not differ between the GG and GT&TT group. In conclusion, the COLIA1 polymorphism in children and young adults is associated with several bone characteristics. However, at least a part of the COLIA1 effect on bone mass may be related to differences in frame size.

Absorptiometry, Photon↗
PubMed2002

Fluorine-18 FDG imaging in hepatocellular carcinoma using positron coincidence detection and single photon emission computed tomography.

BACKGROUND/AIMS: We prospectively evaluated whether fluorine-18 deoxyglucose (FDG) positron coincidence detection (PCD) or FDG single-photon emission computed tomography (SPECT) provides additional benefits to our conventional preoperative evaluation of lesion detection in patients suspected to have hepatocellular carcinoma (HCC). METHODS: Thirteen consecutive patients with a suspected HCC underwent conventional preoperative evaluation with ultrasonography (US), triple-phase helical computed tomography (CT), superparamagnetic iron oxides (SPIO) enhanced magnetic resonance imaging (MRI) and serum alpha-fetoprotein (AFP) level. All 13 patients had an FDG-PCD and SPECT. These results were evaluated to assess the value of FDG-PCD and SPECT in addition to US, SPIO-enhanced MRI and triple-phase helical CT. RESULTS: Ten of the 13 (77%) patients had at least one histologically confirmed HCC without extrahepatic abdominal spread. The tumors ranged in size from 1 to 8 cm and the serum AFP ranged from 3 to 30 000 microg/l. Of these 10 patients, two patients had an increased tumor F-FDG uptake (sensitivity of 20%); one patient with an AFP of 5 microg/l and a tumor size of maximum 4.5 cm and one patient with an AFP of 249 microg/l and a tumor size of maximum 2 cm. In three patients with a benign liver mass, FDG imaging with either PCD or SPECT was negative. There was no false positive finding. CONCLUSIONS: We found poor sensitivity of FDG-PCD and FDG-SPECT for the detection of HCC. There were no clear relations between AFP or tumor size and FDG uptake. Therefore, we conclude that FDG imaging with PCD or SPECT has no value in the preoperative work-up for HCC in patients with cirrhosis.

Adult↗
PubMed2002

Tissue distribution of octreotide binding receptors in normal mice and strains prone to autoimmunity.

Somatostatin has diverse functions, including immunomodulatory functions. In humans, sites of active inflammation can be visualized by the administration of 111In-DTPA(0)-octreotide, a radiolabelled somatostatin analogue. We wished to establish an animal model for preclinical evaluation of the effects of somatostatin analogues on the immune system. However, most animal models for immunological diseases are murine. This report is a preliminary study of the distribution of somatostatin receptors in mouse tissues, with emphasis on the immune system. Tissue distribution of octreotide binding receptors in normal (BALB/c) mice was determined in vivo by receptor binding of 111In-DTPA(0)-octreotide and in vitro and ex vivo by receptor autoradiography. Additionally, we investigated the tissue distribution of octreotide binding receptors in inflammatory lesions in a murine model of immune mediated disease, i.e. pre-diabetic pancreatic infiltration in the non-obese diabetic mouse strain. High specific uptake of radioactivity was seen in the thymus (range 1-1.7% ID/g) and the pituitary (1-1.6% ID/g) in all mouse strains. Specific uptake was also found in the stomach (0.1-0.7% ID/g), in the adrenal glands (0.1-0.3% ID/g) and in the pancreas (0.1-0.3% ID/g). However, we did not detect increased uptake of radiolabelled octreotide in the pancreas of pre-diabetic NOD mice. Autoradiography on tissue sections confirmed the presence of octreotide binding sites in the tissues that showed specific uptake. Moreover, by using autoradiography we could localize the cortex of the thymus and the anterior part of the pituitary as the localization of specific and high affinity, octreotide binding sites. A high, but not a receptor mediated, uptake of radioactivity was seen in the kidneys and was significantly higher in females than in males (12-19% vs 4% ID/g, respectively). Our results point to profound species differences in the tissue distribution of octreotide binding receptors. Of particular interest is the high uptake of 111In-DTPA(0)-octreotide in the cortex of the mouse thymus. This offers perspectives for the use of this animal in studies concerning the effect of somatostatin analogues on the immune system. To our knowledge, this is the first report on the tissue distribution of octreotide binding receptors in mice.

Animals↗
PubMed2002

Reference data for bone density and body composition measured with dual energy x ray absorptiometry in white children and young adults.

AIMS: To obtain normative data on bone mineral density and body composition measured with dual energy x ray absorptiometry (DXA) from early childhood to young adulthood. METHODS: Cross sectional results from 444 healthy white volunteers (4-20 years) in the Netherlands were combined with the results from 198 children who agreed to participate in the follow up study approximately four years later. DXA (Lunar, DPXL) of lumbar spine and total body was performed to assess bone density and body composition. RESULTS: Bone density and lean body mass (LBM) increased with age. Maximal increase in bone density and LBM occurred around the age of 13 years in girls and approximately two years later in boys. Bone density of total body and lumbar spine showed an ongoing slight increase in the third decade. Mean fat percentage in boys remained at 10.5% throughout childhood, but increased in girls. CONCLUSIONS: Most of the skeletal mass in lumbar spine and total body is reached before the end of the second decade, with a slight increase thereafter. This study provides reference values for bone density and body composition measured with DXA for children and young adults.

Absorptiometry, Photon↗