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Background: Patients with high-risk neuroblastoma (NB) have a 5-year event-free survival of less than 50 %, and novel and improved treatment options are needed. Radiolabeled somatostatin analogs (SSTAs) could be a treatment option. The aims of this work were to compare the biodistribution and the therapeutic effects of 177Lu-octreotate and 177Lu-octreotide in mice bearing the human CLB-BAR NB cell line, and to evaluate their regulatory effects on apoptosis-related genes. Methods: The biodistribution of 177Lu-octreotide in mice bearing CLB-BAR tumors was studied at 1, 24, and 168 h after administration, and the absorbed dose was estimated to tumor and normal tissues. Further, animals were administered different amounts of 177Lu-octreotate or 177Lu-octreotide. Tumor volume was measured over time and compared to a control group given saline. RNA was extracted from tumors, and the expression of 84 selected genes involved in apoptosis was quantified with qPCR. Results: The activity concentration was generally lower in most tissues for 177Lu-octreotide compared to 177Lu-octreotate. Mean absorbed dose per administered activity to tumor after injection of 1.5 MBq and 15 MBq was 0.74 and 0.03 Gy/MBq for 177Lu-octreotide and 2.9 and 0.45 Gy/MBq for 177Lu-octreotate, respectively. 177Lu-octreotide treatment resulted in statistically significant differences compared to controls. Fractionated administration led to a higher survival fraction than after a single administration. The pro-apoptotic genes TNSFS8, TNSFS10, and TRADD were regulated after administration with 177Lu-octreotate. Treatment with 177Lu-octreotide yielded regulation of the pro-apoptotic genes CASP5 and TRADD, and of the anti-apoptotic gene IL10 as well as the apoptosis-related gene TNF. Conclusion: 177Lu-octreotide gave somewhat better anti-tumor effects than 177Lu-octreotate. The similar effect observed in the treated groups with 177Lu-octreotate suggests saturation of the somatostatin receptors. Pronounced anti-tumor effects following fractionated administration merited receptor saturation as an explanation. The gene expression analyses suggest apoptosis activation through the extrinsic pathway for both radiopharmaceuticals.

Wild European perch (Perca fluviatilis) is one of the most important freshwater fish species, in Sweden, due to its widespread and his value for recreational fishing. Little it is known regarding the biodistribution of naturally occurring radionuclides such as 238U, 234U, 226Ra, 210Po in perch. Therefore, in this study, perches from five lakes located in different counties in Sweden were collected to investigate the biodistribution of 238U, 234U, 226Ra, 210Po and 137Cs in organs and tissues of perch as well as their radiological impact. The results showed that uranium radionuclides ranged between 0.1 and 6 Bq/kg with an average value of 1.1 ± 1.5 Bq/kg. 226Ra varied from 0.4 to 8 Bq/kg with a mean concentration of 1.7 ± 1.9 Bq/kg. The ranged of 210Po was 0.5 – 250 Bq/kg, with an average value of 24 ± 52 Bq/kg. On the other hand, the highest activity concentration of 137Cs, 151 ± 1 Bq/kg, was detected in muscle samples of perch from Redsjösjön lake. For uranium radionuclides and 226Ra uptake from water is the main source whereas for 210Po and 137Cs the uptake is controlled by the perch diet. Regarding naturally occurring radionuclides, the perch tended to accumulated uranium radionuclides in fins, gills, and skin; 226Ra in bones, fins and skin and 210Po in the organs linked to digestive system. Finally, in case of consumption, it is advised the consumption of skinned fillets of perch due to the higher bioaccumulation of the radionuclides investigated in the skin and scales.

Background: In phenylketonuria (PKU), weaning is considered more challenging when compared to feeding healthy infants. The primary aim of weaning is to gradually replace natural protein from breast milk or standard infant formula with solids containing equivalent phenylalanine (Phe). In addition, a Phe-free second stage L-amino acid supplement is usually recommended from around 6 months to replace Phe-free infant formula. Our aim was to assess different weaning approaches used by health professionals across Europe. Methods: A cross sectional questionnaire (survey monkey®) composed of 31 multiple and single choice questions was sent to European colleagues caring for inherited metabolic disorders (IMD). Centres were grouped into geographical regions for analysis. Results: Weaning started at 17–26 weeks in 85% (n = 81/95) of centres, >26 weeks in 12% (n = 11/95) and 26 weeks. First solids were mainly low Phe vegetables (59%, n = 56/95) and fruit (34%, n = 32/95).A Phe exchange system to allocate dietary Phe was used by 52% (n = 49/95) of centres predominantly from Northern and Southern Europe and 48% (n = 46/95) calculated most Phe containing food sources (all centres in Eastern Europe and the majority from Germany and Austria). Some centres used a combination of both methods.A second stage Phe-free L-amino acid supplement containing a higher protein equivalent was introduced by 41% (n = 39/95) of centres at infant age 26–36 weeks (mainly from Germany, Austria, Northern and Eastern Europe) and 37% (n = 35/95) at infant age > 1y mainly from Southern Europe. 53% (n = 50/95) of centres recommended a second stage Phe-free L-amino acid supplement in a spoonable or semi-solid form. Conclusions: Weaning strategies vary throughout European PKU centres. There is evidence to suggest that different infant weaning strategies may influence longer term adherence to the PKU diet or acceptance of Phe-free L-amino acid supplements; rendering prospective long-term studies important. It is essential to identify an effective weaning strategy that reduces caregiver burden but is associated with acceptable dietary adherence and optimal infant feeding development. Keywords: Weaning, Infant, Phenylketonuria, Phenylalanine, Phe-free infant formula

Background: In infants with phenylketonuria (PKU), dietary management is based on lowering and titrating phenylalanine (Phe) intake from breast milk or standard infant formula in combination with a Phe-free infant formula in order to maintain blood Phe levels within target range. Professionals use different methods to feed infants with PKU and our survey aimed to document practices across Europe. Methods: We sent a cross sectional, survey monkey® questionnaire to European health professionals working in IMD. It contained 31 open and multiple-choice questions. The results were analysed according to different geographical regions. Results: Ninety-five centres from 21 countries responded. Over 60% of centres commenced diet in infants by age 10 days, with 58% of centres implementing newborn screening by day 3 post birth. At diagnosis, infant hospital admission occurred in 61% of metabolic centres, mainly in Eastern, Western and Southern Europe. Breastfeeding fell sharply following diagnosis with only 30% of women still breast feeding at 6 months.53% of centres gave pre-measured Phe-free infant formula before each breast feed and 23% alternated breast feeds with Phe-free infant formula. With standard infant formula feeds, measured amounts were followed by Phe-free infant formula to satiety in 37% of centres (n = 35/95), whereas 44% (n = 42/95) advised mixing both formulas together. Weaning commenced between 17 and 26 weeks in 85% centres, ≥26 weeks in 12% and

In Sweden, around 20 % of the potable water comes from groundwater sources and about one million people drink water from their private wells. In areas with moderate or high abundance of naturally occurring radionuclides in the bedrock, the groundwater could be enhanced with radio and chemically toxic elements such as uranium, radium, lead and polonium. Therefore, this study aims to carry out a comprehensive analysis of the behaviour and radiological impact of naturally occurring radionuclides in well water. For that, a well water survey was done in 2020 along Sweden, focusing the study on the determination of 210 Po, 210 Pb, 226 Ra, 228 Ra, 238 U and 234 U by alpha spectrometry. The results of the present study showed that the naturally occurring radionuclides distributions in the well water investigated were highly variable. In addition, the radionuclides with the highest contribution to the indicative dose were 210 Pb >  228 Ra >  210 Po >  226 Ra >  234 U >  238 U. On the other hand, the filtration and aeration purification treatment could help to remediate the radiological impact. However, the dose assessment results point out the need to include well water in the framework of the current regulations of requirements for the protection of the health of the public regarding radioactive substances in water intended for human consumption, to guarantee the quality of water from the radiological point of view., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Wild European perch (Perca fluviatilis) is one of the most important freshwater fish species, in Sweden, due to its widespread and his value for recreational fishing. Little it is known regarding the biodistribution of naturally occurring radionuclides such as 238 U, 234 U, 226 Ra, 210 Po in perch. Therefore, in this study, perches from five lakes located in different counties in Sweden were collected to investigate the biodistribution of 238 U, 234 U, 226 Ra, 210 Po and 137 Cs in organs and tissues of perch as well as their radiological impact. The results showed that uranium radionuclides ranged between 0.1 and 6 Bq/kg with an average value of 1.1 ± 1.5 Bq/kg. 226 Ra varied from 0.4 to 8 Bq/kg with a mean concentration of 1.7 ± 1.9 Bq/kg. The ranged of 210 Po was 0.5 - 250 Bq/kg, with an average value of 24 ± 52 Bq/kg. On the other hand, the highest activity concentration of 137 Cs, 151 ± 1 Bq/kg, was detected in muscle samples of perch from Redsjösjön lake. For uranium radionuclides and 226 Ra uptake from water is the main source whereas for 210 Po and 137 Cs the uptake is controlled by the perch diet. Regarding naturally occurring radionuclides, the perch tended to accumulated uranium radionuclides in fins, gills, and skin; 226 Ra in bones, fins and skin and 210 Po in the organs linked to digestive system. Finally, in case of consumption, it is advised the consumption of skinned fillets of perch due to the higher bioaccumulation of the radionuclides investigated in the skin and scales., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Patients with neuroendocrine tumors expressing somatostatin receptors are often treated with 177 Lu[Lu]-octreotate. Despite being highly effective in animal models, 177 Lu[Lu]-octreotate-based therapies in the clinical setting can be optimized further. The aims of the study were to identify and elucidate possible optimization venues for 177 Lu[Lu]-octreotate tumor therapy by characterizing transcriptional responses in the GOT1 small intestine neuroendocrine tumor model in nude mice., Methods: GOT1-bearing female BALB/c nude mice were intravenously injected with 15 MBq 177 Lu[Lu]-octreotate (non-curative amount) or mock-treated with saline solution. Animals were killed 1, 3, 7 or 41 d after injection. Total RNA was extracted from the tumor samples and profiled using Illumina microarray expression analysis. Differentially expressed genes were identified (treated vs. control) and pathway analysis was performed., Results: Distribution of differentially expressed transcripts indicated a time-dependent treatment response in GOT1 tumors after 177 Lu[Lu]-octreotate administration. Regulation of CDKN1A, BCAT1 and PAM at 1 d after injection was compatible with growth arrest as the initial response to treatment. Upregulation of APOE and BAX at 3 d, and ADORA2A, BNIP3, BNIP3L and HSPB1 at 41 d after injection suggests first activation and then inhibition of the intrinsic apoptotic pathway during tumor regression and regrowth, respectively., Conclusion: Transcriptional analysis showed radiation-induced apoptosis as an early response after 177 Lu[Lu]-octreotate administration, followed by pro-survival transcriptional changes in the tumor during the regrowth phase. Time-dependent changes in cell cycle and apoptosis-related processes suggest different time points after radionuclide therapy when tumor cells may be more susceptible to additional treatment, highlighting the importance of timing when administering multiple therapeutic agents., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: In the present investigation, microarray analysis was used to monitor transcriptional activity in thyroids in mice 24 h after (131)I exposure. The aims of this study were to 1) assess the transcriptional patterns associated with (131)I exposure in normal mouse thyroid tissue and 2) propose biomarkers for (131)I exposure of the thyroid., Methods: Adult BALB/c nude mice were i.v. injected with 13, 130 or 260 kBq of (131)I and killed 24h after injection (absorbed dose to thyroid: 0.85, 8.5, or 17 Gy). Mock-treated mice were used as controls. Total RNA was extracted from thyroids and processed using the Illumina platform., Results: In total, 497, 546, and 90 transcripts were regulated (fold change ≥1.5) in the thyroid after 0.85, 8.5, and 17 Gy, respectively. These were involved in several biological functions, e.g. oxygen access, inflammation and immune response, and apoptosis/anti-apoptosis. Approximately 50% of the involved transcripts at each absorbed dose level were dose-specific, and 18 transcripts were commonly detected at all absorbed dose levels. The Agpat9, Plau, Prf1, and S100a8 gene expression displayed a monotone decrease in regulation with absorbed dose, and further studies need to be performed to evaluate if they may be useful as dose-related biomarkers for 131I exposure., Conclusion: Distinct and substantial differences in gene expression and affected biological functions were detected at the different absorbed dose levels. The transcriptional profiles were specific for the different absorbed dose levels. We propose that the Agpat9, Plau, Prf1, and S100a8 genes might be novel potential absorbed dose-related biomarkers to (131)I exposure of thyroid., Advances in Knowledge: During the recent years, genomic techniques have been developed; however, they have not been fully utilized in nuclear medicine and radiation biology. We have used RNA microarrays to investigate genome-wide transcriptional regulations in thyroid tissue in mice after low, intermediate, and high absorbed doses from (131)I exposure in vivo. Using this approach, we have identified novel biological responses and potential absorbed dose-related biomarkers to (131)I exposure. Our research shows the importance of embracing technological advances and multi-disciplinary collaboration in order to apply them in radiation therapy, nuclear medicine, and radiation biology., Implications on Patient Care: This work may contribute with new knowledge of potential normal tissue effects or complications that may occur after exposure to ionizing radiation in diagnostic and therapeutic nuclear medicine, and due to radioactive fallout or accident with radionuclide spread., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: The kidneys are the dose-limiting organs in some radionuclide therapy regimens. However, the biological impact of internal exposure from radionuclides is still not fully understood. The aim of this study was to examine the effects of dose rate and time after i.v. injection of (177)LuCl3 on changes in transcriptional patterns in mouse kidney tissue., Methods: To investigate the effect of dose rate, female Balb/c nude mice were i.v. injected with 11, 5.6, 1.6, 0.8, 0.30, and 0 MBq of (177)LuCl3, and killed at 3, 6, 24, 48, 168, and 24 hours after injection, respectively. Furthermore, the effect of time after onset of exposure was analysed using mice injected with 0.26, 2.4, and 8.2 MBq of (177)LuCl3, and killed at 45, 90, and 140 days after injection. Global transcription patterns of irradiated kidney cortex and medulla were assessed and enriched biological processes were determined from the regulated gene sets using Gene Ontology terms., Results: The average dose rates investigated were 1.6, 0.84, 0.23, 0.11 and 0.028 mGy/min, with an absorbed dose of 0.3 Gy. At 45, 90 and 140 days, the absorbed doses were estimated to 0.3, 3, and 10 Gy. In general, the number of differentially regulated transcripts increased with time after injection, and decreased with absorbed dose for both kidney cortex and medulla. Differentially regulated transcripts were predominantly involved in metabolic and stress response-related processes dependent on dose rate, as well as transcripts associated with metabolic and cellular integrity at later time points., Conclusion: The observed transcriptional response in kidney tissue was diverse due to difference in absorbed dose, dose rate and time after exposure. Nevertheless, several transcripts were significantly regulated in all groups despite differences in exposure parameters, which may indicate potential biomarkers for exposure of kidney tissue., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: The kidneys are one of the main dose limiting organs in (177)Lu-octreotate therapy of neuroendocrine tumors. Therefore, biomarkers for radiation damage would be of great importance in this type of therapy. The purpose of this study was to investigate the absorbed dose dependency on early transcriptional changes in the kidneys from (177)Lu-octreotate exposure., Methods: Female Balb/c nude mice were i.v. injected with 1.3, 3.6, 14, 45 or 140 MBq (177)Lu-octreotate. The animals were killed 24 h after injection followed by excision of the kidneys. The absorbed dose to the kidneys ranged between 0.13 and 13 Gy. Total RNA was extracted from separated renal tissue samples, and applied to Illumina MouseRef-8 Whole-Genome Expression Beadchips to identify regulated transcripts after irradiation. Nexus Expression 2.0 and Gene Ontology terms were used for data processing and to determine affected biological processes., Results: Distinct transcriptional responses were observed following (177)Lu-octreotate administration. A higher number of differentially expressed transcripts were observed in the kidney medulla (480) compared to cortex (281). In addition, 39 transcripts were regulated at all absorbed dose levels in the medulla, compared to 32 in the cortex. Three biological processes in the cortex and five in the medulla were also shared by all absorbed dose levels. Strong association to metabolism was found among the affected processes in both tissues. Furthermore, an association with cellular and developmental processes was prominent in kidney medulla, while transport and immune response were prominent in kidney cortex., Conclusion: Specific biological and dose-dependent responses were observed in both tissues. The number of affected transcripts and biological processes revealed distinct response differences between the absorbed doses delivered to the tissues., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: In peptide receptor radionuclide therapy for neuroendocrine tumors the main dose-limiting tissue is found in the kidneys because of tubular reabsorption and retention of radioactivity. The aim of this study was to quantify late effects in renal cortex of nude mice exposed to high amounts of [(177)Lu]-DOTA-Tyr(3)-octreotate ([(177)Lu]-DOTATATE), and to determine whether a threshold dose value exists for these findings., Methods: Nude mice were exposed to 90, 120 or 150 MBq of [(177)Lu]-DOTATATE. Renal toxicity was evaluated up to 6 months after injection. Blood samples were collected to examine renal functional markers, and after sacrifice at 6 months changes in renal morphology were explored. Tissue damage was estimated by quantifying the relative area of the different subunits in the renal cortex using point counting. Additional morphological signs of radiation damage were also noted. The absorbed doses to the kidneys were estimated by previously determined kidney pharmacokinetics and Monte Carlo simulations for different assumptions regarding the activity distribution., Results: Increased serum creatinine and urea values indicated long-term renal toxicity. The tissue area occupied by proximal tubules decreased with increasing doses of [(177)Lu]-DOTATATE, whereas the other subunits in cortex slightly increased. The mean absorbed dose in the renal cortex for [(177)Lu]-DOTATATE was estimated to be 35-58 Gy for the different groups of animals. A dose-response relationship was observed for proximal tubular damage, and a threshold dose value of 24 Gy (BED 37 Gy) was determined., Conclusions: Selective morphological changes in kidney cortex of nude mice were quantified and appeared in a dose dependent manner after injection of high amounts of [(177)Lu]-DOTATATE., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: Astatine ((211)At; alpha-emitter; t(1/2)=7.21 h) shares several features with its halogen neighbour iodine. In the present study, we investigated whether 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) can be used to increase the cellular retention time of (211)At and radioiodide in thyroid epithelial cells., Methods: The transepithelial transport and cellular uptake of (211)At and (125)I(-) were studied simultaneously in porcine thyrocytes cultured in bicameral chambers. The cells were prestimulated with thyroid-stimulating hormone (TSH) or epidermal growth factor (EGF) for 48 h. In addition, the acute effects of DIDS and forskolin were investigated., Results: The transepithelial transport of both radionuclides was stimulated by TSH and down-regulated by EGF. DIDS rapidly reduced the efflux and increased the cellular content of (125)I(-) in control and TSH-stimulated cells, whereas DIDS had no effect on (125)I(-) transport in EGF-treated cells. DIDS blocked the (211)At efflux only in TSH-stimulated cells. Unexpectedly, DIDS caused an accelerated efflux of (211)At in both control and EGF-stimulated cells and, furthermore, reduced the cellular content of (211)At in the EGF-stimulated cultures. DIDS had no effect on the forskolin-induced efflux of the two radionuclides., Conclusions: The magnitude of thyroidal (211)At uptake and efflux is similar to that of (125)I(-), strongly dependent on the functional activity of the cells. However, (211)At efflux likely involves several permeating mechanisms with different sensitivity to DIDS, which are at least partly not shared by (125)I(-). The results suggest that anion channel blockage is potentially useful to increase the absorbed dose from both (211)At and radioiodine in NIS-expressing tumours.

Susceptibility differences are common causes for artifacts in magnetic resonance (MR); therefore, it is important to choose phantom materials in a way that these artifacts are kept at a minimum. In this study, a previously proposed MR imaging (MRI) method [Beuf O, Briguet A, Lissac M, Davis R. Magnetic resonance imaging for the determination of magnetic susceptibility of materials. J Magn Reson 1996; Series B(112):111-118] was improved to facilitate sensitive in-house measurements of different phantom materials so that such artifacts can more easily be minimized. Using standard MRI protocols and distilled water as reference, we measured magnetic volume susceptibility differences with a clinical MR system. Two imaging techniques, echo planar imaging (EPI) and spin echo, were compared using liquid samples whose susceptibilities were verified by MR spectroscopy. The EPI sequence has a very narrow bandwidth in the phase-encoding direction, which gives an increased sensitivity to magnetic field inhomogeneities. All MRI measurements were evaluated in two ways: (1) manual image analysis and (2) model fitting. The narrow bandwidth of the EPI made it possible to detect very small susceptibility differences (equivalent susceptibility difference, Deltachi(e)> or =0.02 ppm), and even plastics could be measured. Model fitting yielded high accuracy and high sensitivity and was less sensitive to other image artifacts as compared with manual image analysis.

Background: The internalization of radiolabeled somatostatin analogs into tumor cells is of great importance for radionuclide therapy. It has previously been shown that some radiolabeled somatostatin analogs are internalized through receptor-mediated endocytosis. The development of methods that increase the number of receptors on tumor cells is important to further improve the internalization of radionuclides. The aim of this study was to investigate the possibility of inducing up-regulation of the somatostatin receptor (sstr) expression on tumor cells by external-beam irradiation., Methods: Human small cell lung cancer (SCLC) cells were irradiated to absorbed doses of 2-8 Gy, and the uptake of 177Lu-DOTA-Tyr3-octreotate was measured 1-7 days after irradiation. The sstr2 mRNA expression was determined by quantitative reverse transcriptase-polymerase chain reaction., Results: The uptake of 177Lu-DOTA-Tyr3-octreotate was 1.5-3 times higher in cells irradiated to 4 Gy than in nonirradiated cells, and the highest uptake occurred 1 and 3-5 days after irradiation. The uptake of 177Lu-DOTA-Tyr3-octreotate was similar for cells irradiated to 2, 4, 6 and 8 Gy. The sstr2 mRNA expression was twice as high in the cells irradiated to 4 Gy than in the nonirradiated cells., Conclusions: The uptake of 177Lu-DOTA-Tyr3-octreotate increased in SCLC cells after exposure to irradiation, probably due to up-regulation of sstr expression. These results may be important in optimizing the treatment of tumors expressing sstr using radiolabeled somatostatin analogs.

In nude mice carrying the human carcionoid GOT1 different amounts of (111)In-DTPA-Phe(1)-octreotide and routes of administration were studied in relation to uptake in tumor and normal organs. The relative organ uptake varied with given amount; highest in tumor after 0.1 and 1 microg and lowest in muscle, heart and blood after 0.1 microg. The uptake decreased in lungs and spleen with higher amounts of (111)In-DTPA-Phe(1)-octreotide. In all organs studied the tumor-to-normal-tissue activity concentration ratio was maximal at 0.1 and 1 microg, but route of administration influenced the uptake only little.

2D MRSI suffers from the effect of the spatial response function due to the truncation of the sampling of k-space. Filtering of the k-space data-set is often used to suppress the side lobes caused by the effects of the SRF, where the sampled data-set is multiplied with a weighting function before inverse FT. Commonly used filters in MRSI are the cosine, Hanning and Hamming filters. The data-set is often interpolated into a larger image matrix size for analysis, where "Fourier interpolation" (FoI) and "cubic spline interpolation" (CSpI) are two common methods. In this work, the effects of k-space filtering in practical usage was examined, and the image representations of the object for the two interpolation methods were compared. This study showed that application of filtering improves the image representation of the structures in the object and should be used in MRSI. FoI correctly visualizes the information inherent in the data-set, while the features of the object were dependent on the position of the object relative the original matrix in the CSpI interpolated images. FoI should therefore be used for quantitative evaluation of MRSI images.

A human midgut carcinoid tumor was successfully transplanted into nude mice and propagated for five consecutive generations (30 months) with well-preserved phenotype. Tumor cells in nude mice expressed identical neuroendocrine markers as the original tumor, including somatostatin receptors (somatostatin receptors 1 to 5) and vesicular monoamine transporters (VMAT1 and VMAT2). Because of the expression of somatostatin receptors and VMAT1 and VMAT2 the grafted tumors could be visualized scintigraphically using the somatostatin analogue 111In-octreotide and the catecholamine analogue 123I-metaiodobenzylguanidine. The biokinetics of the somatostatin analogue 111In-octreotide in the tumors was studied and showed a high retention 7 days after administration. Cell cultures were re-established from transplanted tumors. Immunocytochemical and ultrastructural studies confirmed the neuroendocrine differentiation. The human origin of transplanted tumor cells was confirmed by cytogenetic and fluorescence it situ hybridization analyses. Spontaneous secretion of serotonin and its metabolite, 5-hydroxyindole acetic acid, from tumor cells was demonstrated. The tumor cells increased their [Ca2+]i in response to beta-adrenoceptor stimulation (isoproterenol) and K+-depolarization. All somatostatin receptor subtypes could be demonstrated in cultured cells. This human transplantable carcinoid tumor, designated GOT1, grafted to nude mice, will give unique possibilities for studies of somatostatin receptor- and VMAT-mediated radionuclide uptake as well as for studies of secretory mechanisms.

The long time biokinetics of the radiolabeled somatostatin analogues 111In-DTPA-D-Phe(1)-octreotide was studied in nude mice transplanted with the human carcinoid tumor, GOT1. The results were compared with those from the patient with the original tumor. This patient has been diagnosed and later treated with 111In-DTPA-D-Phe(1)-octreotide. The animals received about 2 MBq 111In-DTPA-D-Phe(1)-octreotide (0.1 microg) by injection into a tail vein. The animals were killed 0.5 h-14 d after injection of the radiopharmaceutical. Tumor tissue and normal tissues were collected and weighed and measured for 111In activity. The 111In uptake in the tumor was higher than in all normal tissues except the kidneys. The tumor-to-normal-tissue activity concentration, TNC, increased with time for all normal tissues studied. These data were similar to those observed for the original tumor in the patient. The similar biokinetics for 111In-DTPA-D-Phe(1)-octreotide in the tumor-bearing mice and the patient makes this animal model suitable as a model for evaluation of therapy of somatostatin receptor (sstr) expressing tumors with radiolabeled somatostatin analogues. Furthermore, the increase with time of TNC both in mice and the patient indicates that long-lived radionuclides are preferred for therapy with radiolabeled somatostatin analogues.

The transport and accumulation of free 211At and 125I- were investigated in thyrocytes cultured as monolayers in bicameral chambers under the influence of thyroid-stimulating hormone, stable iodide, ouabain and perchlorate. The results indicate that there are similarities and differences in the transport mechanisms of free 211At and 125I-. These results will be valuable in the development of radiation protection when handling and using 211At-labeled radiopharmaceuticals, and for the potential use of free 211At in radiation therapy of poorly differentiated thyroid cancer.

The purpose was to analyse magnetic susceptibility effects on accuracy of point-wise measurements of signal profiles in the assessment of MRS volume selection performance. An existing phantom design consisting of a sphere with a movable signal source was used for the investigation. The influence from the phantom on magnetic field homogeneity was measured with phase sensitive 1H imaging and 31P spectroscopy on a 1.5 T whole body MR system. The susceptibility effects for such a phantom design can be separated in 1/ A variation in the background magnetic field, which is caused by the stationary structures and has a significant influence on spatial accuracy. 2/ A magnetic field distortion, which is caused by the movable signal source and has very little influence on accuracy. The spatial inaccuracy due to susceptibility effects in this phantom, was 0.03 mm for positions of the signal source covering a 40-mm VOI. Susceptibility effects from the movable signal source were substantial but had very little influence on spatial accuracy. Still, improvements of this phantom design are possible. Point-wise measurements using a phantom with a movable signal source is inherently insensitive to susceptibility effects from the signal source and permits accurate signal profile measurements of high spatial (sub-mm) resolution.

A method for production of carrier-free (114m)In (half-life 49.5 days), which is a potential radionuclide for radionuclide therapy of slowly growing tumors, is presented. A target consisting of five enriched cadmium ((114)Cd) foils, each 50 microm thick, was irradiated by protons (from 12.6-6.5 MeV) giving a target yield of 0. 8 MBq/microAh. A simple and cost-efficient thermal diffusion method was used for the separation. The irradiated target foils were heated for 2 h at 306 degrees C and then etched in 0.05 M HCl. The obtained cadmium/indium solution was purified using a cation ion-exchange resin (AG 1 x 8, Bio-Rad Laboratories, Hercules, CA USA). An overall yield of approximately 60% was obtained, whereas the loss of the target material was <1% per separation cycle. The (114m)In production gave (114m)In with high specific radioactivity and was successfully used to label diethylenetriamine pentaacetic acid (DTPA)-D-Phe-octreotide. Furthermore, no difference in biodistribution between [(114m)In]- and [(111)In]-DTPA-D-Phe(1)-octreotide in tumor-bearing nude mice was seen. The high radionuclide uptake in the tumors indicates a good receptor binding of the labeled octreotide.

This paper deals with some of the practical considerations in the planning and performance of chemical shift imaging (MRSI or CSI) of the brain. It contains some aspects of 1) the imaging procedure (MRI), i.e., suggestions of an imaging protocol useful for the spectroscopic planning, 2) the planning of the spectroscopic volume, i.e., size and position, 3) evaluation and judgment of the preparation results, and 4) evaluation of the MRSI images. The paper also contains suggestions of developmental work and quality assessment to be done before patient studies are begun. Examples are given for MRSI studies of temporal lobe epilepsy. Several of the aspects described are obvious for the experienced spectroscopist but may be useful in the initiation of MRSI. The goal of this paper was to share our experiences of how to achieve high quality MRSI, experiences that we would had been grateful for in our prelude of MRSI experiments.

The difference between the experimental and theoretical spatial response function (SRF) of a narrow tube with water is used for a localization test for magnetic resonance spectroscopic imaging (MRSI). From this difference a quantitative performance parameter is derived for the relative amount of signal within a limited region in the field of view. The total signal loss by the MRSI experiment and eddy currents is described by a parameter SL derived from the signal intensities of two echoes. Results of a European multi-centre trial show that this approach is suited for assessment of MRSI localization performance.

The volume-selection performance was studied for single- and double-volume-of-interest (VOI) acquisition with the volume-selection method image-selected in vivo spectroscopy for 31P magnetic resonance spectroscopy. High-resolution signal profiles were measured using a phantom simulating a brain. Inside the phantom there was a small, remotely controlled, movable signal source filled with ortho-phosphoric acid. Signal profiles of the VOI were measured in three perpendicular directions for 1VOI (single VOI) and 2VOI (double VOI) acquisition. The measured signal profiles for both acquisitions were very similar, but they showed a discrepancy with regard to the intended VOI (iVOI). The transition regions were on average 3.8 mm and the average full width at half maximum of the signal profile was 30 mm for an iVOI size of 30*30*30 (mm3). No displacement was observed in the signal profiles. To avoid overlapping signal profiles, the minimum separation between two iVOIs was found to be 10 mm in our magnetic resonance (MR) system. A substantial negative signal contribution from regions outside the iVOI was measured in the y-direction for 1VOI acquisition and one of the two VOIs in 2VOI acquisition. The other VOI in 2VOI acquisition exhibited only minor contamination. The measurements presented underline the importance of detailed knowledge on the volume selection performance in in vivo magnetic resonance spectroscopy.

A monoclonal antibody, C215, was first internally labelled with 75Se-methionine and then labelled with 125I. The biodistribution of the dual-labelled [125I][75Se]C215 was studied in tumour-bearing nude mice killed 3 days after injection. The biodistribution of the dual-labelled [125I][75Se]C215 was compared with the biodistribution of single-labelled [131I]C215 and [75Se]C215. Iodine-labelled antibodies seem to be damaged during iodination, affecting the disappearance rate and tumour uptake. There were no signs of dehalogenation of circulating antibodies or antibodies taken up in the tumour.