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R Dudczak

Publications and source records attributed to R Dudczak.

At least 19 recordsLinked to original sources
PubMed2003

Autoimmune diseases in vitiligo: do anti-nuclear antibodies decrease thyroid volume?

An increased prevalence of autoimmune thyroiditis (AT) in vitiligo patients is well known. The aim of this study was firstly, to evaluate the clinical course of patients with both vitiligo and AT and secondly, to identify additional autoimmune disorders affecting the thyroid gland in a large cohort of vitiligo patients. We analysed a study group of 106 vitiligo patients and 38 controls. A detailed thyroid examination including sonography was performed in all study participants. In addition, the study participants were HLA typed and screened for various autoimmune disorders. AT was significantly more frequent in vitiligo patients than in controls (21%versus 3%; P < 0.01). In 12 of the 22 patients with AT, vitiligo was the initial disease preceding AT by 4-35 years. In the other 10 patients with AT, both vitiligo and AT were diagnosed within one year. There were two individuals with diabetes mellitus type 1 and a single patient with Addison's disease. Anti-nuclear antibody (ANA), anti-smooth muscle cell antibody, and parietal cell antibody levels occurred with a similar frequency in patients and controls. In all vitiligo patients with both elevated ANA levels and AT (n = 6), the atrophic but not the goitrous variant was diagnosed. These vitiligo patients with both AT and elevated ANA levels had a significantly smaller thyroid volume compared to the vitiligo patients with AT whose ANA levels were normal (6.7 +/- 4.5 ml versus 13.4 +/- 9.1 ml, respectively; P < 0.05). The same was found in the entire study group: Thyroid volume of all vitiligo patients (with or without concomitant AT) was significantly smaller in the presence of ANA (6.9 +/- 5.3 versus 10.5 +/- 5.9 ml, respectively; P < 0.05). However, this phenomenon was not observed in the control group. There was a trend for a decreased frequency of HLA-DR3 (6.7%versus 23%) in our study group, but after correction for the number of comparisons, no HLA-allele was statistically significant associated neither with vitiligo nor with multiple autoimmune diseases in our patient sample. Our findings suggest that AT is the most frequent autoimmune disease associated with vitiligo. In our patients, AT presented simultaneously or after the onset of vitiligo but not before. Elevated ANA levels were associated with the atrophic variant of AT and may affect the volume of the thyroid gland, and there was no statistically significant association with the HLA system.

Adolescent↗
PubMed2003

Imaging gastrointestinal tumours using vascular endothelial growth factor-165 (VEGF165) receptor scintigraphy.

BACKGROUND: Recent studies have shown that vascular endothelial growth factor (VEGF) receptor is overexpressed in vascular endothelial cells of various human tumours as well as in human tumour cells. The aim of this study was to evaluate the usefulness of scanning with VEGF(165) labeled with (123)I for tumor localisation in patients with gastrointestinal tumours. PATIENTS AND METHODS: Human recombinant VEGF(165) was radiolabelled with (123)I by electrophilic radioiodination using the chloramine T method. [(123)I]VEGF(165) was administered intravenously [mean dose 184 +/- 18 MBq (</=130 pmol; </=5 micro g) per patient] to 18 patients with gastrointestinal tumours. Dynamic acquisition was initiated immediately after administration and carried out until 30 min post-injection. Whole body images were done in anterior and posterior views at various time points. All patients underwent single-photon emission tomography imaging 1.5 h post-injection. Scanning with [(123)I]VEGF(165) was compared with computed tomography and magnetic resonance imaging. RESULTS: Intravenous injection of [(123)I]VEGF(165) did not cause any side-effects. Binding of [(123)I]VEGF(165 )to primary tumours and metastases was visible shortly after injection. In patients with pancreatic adenocarcinomas, primary tumours were visualised in seven of nine, lymph node metastases in three of four, liver metastases in three of six and lung metastases in one of three. Cholangiocarcinomas were visualised by imaging in one of two patients. Hepatocellular carcinomas were visible by imaging in two of four patients. [(123)I]VEGF(165) scans were weakly positive in one patient with abdominal schwannoma and in one patient with peritoneal carcinosis. CONCLUSIONS: These results indicate that scanning with [(123)I]VEGF(165) can visualise gastrointestinal tumours and metastases expressing receptors for VEGF(165). [(123)I]VEGF(165) receptor scintigraphy may be useful for visualisation of tumour angiogenesis.

Cohort Studies↗
PubMed2002

Positron emission tomography with [18F]2-fluoro-D-2-deoxyglucose (FDG-PET) predicts relapse of malignant lymphoma after high-dose therapy with stem cell transplantation.

We have determined the predictive value of [18F]2-fluoro-2-deoxy-glucose (FDG-PET) in patients with Hodgkin's disease (HD) and aggressive non-Hodgkin's lymphoma (NHL) scheduled for high-dose therapy with stem cell transplantation (HDT/SCT). Inclusion criteria were the presence of an FDG-PET scan after chemotherapy (ChT) within 8 weeks prior to HDT/SCT and available follow-up data. Sixteen patients (10 NHL and six HD) were observed during a follow-up period of 4 to 28 months (median 13 months). Before SCT, five patients had a negative PET, three were weakly positive, two moderately positive, and six strongly positive. None of the five patients with a negative PET before HDT/SCT relapsed and two of three patients with a weakly positive scan are still in remission after HDT/SCT. Of eight patients with a moderate or high positive PET before HDT/SCT, seven relapsed and one died of early HDT/SCT related complications (P< 0.01). Three of eight relapsing patients died of lymphoma 5 to 10 months after SCT and in one additional patient not responding to HDT/SCT, the main cause of death was chronic toxicity 4 months after transplantation. After 12 months, in PET-negative patients the overall and relapse-free survival was 100%, in PET-positive patients 55% and 18%, respectively. In NHL, two patients with negative PET, but with an age-adjusted international prognostic index (AaIPI) of 2 and one with AaIPI = 1 are still in remission. In the seven PET-positive subjects, one patient with AaIPI = 0, three with AaIPI = 1, and two with AaIPI = 2 relapsed. We conclude that FDG-PET is accurate in the prediction of relapse prior to HDT/SCT in patients with lymphoma. It provides additional information when compared with the AaIPI.

Adult↗
PubMed2002

[Value of a structured report for the interpretation of parathyroid scintigraphy in primary essential hyperthyroidism].

The aim of the study was to evaluate whether a four-stage report scheme increases the diagnostic accuracy of dual phase Tc-99 m sestamibi scintigraphy (MIBI-scintigraphy) in patients with primary hyperparathyroidism (pHPT). We analysed the scans of 35 patients with primary hyperparathyroidism referred for Tc-99 m sestamibi scintigraphy and compared them with the sonographic and surgical findings. All scans were interpreted following a four-stage report scheme: Group A--typical scintigraphic findings of a single gland disease, group B--scan consistent with single gland disease, group C--multiple gland disease, group D--non diagnostic scan. Twenty-three scans were ranked in group A. In all these patients, scintigraphy diagnosed both the side and the localization of the adenoma correctly. Sonography made the correct diagnosis in 21/23 individuals and showed false-positive results in 2/23 cases. Group B included 10 scans. In 7/10 individuals, both the side and the localization of the adenoma were diagnosed correctly, whereas in 2/10 patients only the side was diagnosed. The scan of a single patient with hyperplasia of all 4 parathyroid glands was falsely interpreted as "consistent with a left caudal single gland disease". Sonography made the correct diagnosis in 8/10 cases, two individuals were diagnosed as false positive and false negative, respectively. No scan was interpreted as multiple gland disease (group C) and two scans were non diagnostic (group D). Both patients of the last group were correctly diagnosed by sonography. These findings suggest that in case of typical scintigraphic findings of single gland disease, scintigraphy but not sonography should be the primary localization technique for minimally invasive parathyroidectomy.

Adenoma↗
PubMed2002

Experience with indium-111 and yttrium-90-labeled somatostatin analogs.

The high level expression of somatostatin receptors (SSTR) on various tumor cells has provided the molecular basis for successful use of radiolabeled octreotide / lanreotide analogs as tumor tracers in nuclear medicine. Other (nontumoral) potential indications for SSTR scintigraphy are based on an increased lymphocyte binding at sites of inflammatory or immunologic diseases such as thyroid-associated ophthalmology. The vast majority of human tumors seem to over-express the one or the other of five distinct hSSTR subtype receptors. Whereas neuroendocrine tumors frequently overexpress hSSTR2, intestinal adenocarcinomas seem to overexpress more often hSSTR3 or hSSTR4, or both of these hSSTR. In contrast to In-DTPA-DPhe(1)-octreotide (OctreoScan(R)) which binds to hSSTR2 and 5 with high affinity (Kd 0.1-5 nM), to hSSTR3 with moderate affinity (K(d) 10-100 nM) and does not bind to hSSTR1 and hSSTR4, (111)In / (90)Y-DOTA-lanreotide was found to bind to hSSTR2, 3, 4, and 5 with high affinity, and to hSSTR1 with lower affinity (K(d) 200 nM). Based on its unique hSSTR binding profile, (111)In-DOTA-lanreotide was suggested to be a potential radioligand for tumor diagnosis, and (90)Y-DOTA-lanreotide suitable for receptor-mediated radionuclide therapy. As opposed to (111)In-DTPA-DPhe(1)-octreotide and (111)In-DOTA-DPhe(1)-Tyr(3)-octreotide, discrepancies in the scintigraphic results were seen in about one third of (neuroendocrine) tumor patients concerning both the tumor uptake as well as detection of tumor lesions. On a molecular level, these discrepancies seem to be based on a "higherrdquuo; high-affinity binding of (111)In-DOTA-DPhe(1)-Tyr(3)-octreotide to hSSTR2 (K(d) 0.1-1 nM). Other somatostatin analogs with divergent affinity to the five known hSSTR subtype receptors have also found their way into the clinics, such as (99m)Tc-depreotide (NeoSpect(R); NeoTect(R)). Most of the imaging results are reported for neuroendocrine tumors (octreotide analogs) or nonsmall cell lung cancer ((99m)Tc-depreotide), indicating high diagnostic cabability of this type of receptor tracers. Consequently to their use as receptor imaging agents, hSSTR recognizing radioligands have also been implemented for experimental receptor-targeted radionuclide therapy. Beneficial results were reported for high-dose treatment with (111)In-DTPA-DPhe(1)-octreotide, based on the emission of Auger electrons. The Phase IIa study "MAURITIUS" (Multicenter Analysis of a Universal Receptor Imaging and Treatment Initiative, a eUropean Study) showed in progressive cancer patients (therapy entry criteria) with a calculated tumor dose > 10 Gy / GBq (90)Y-DOTA-lanreotide, the proof-of-principle for treating tumor patients with peptide receptor imaging agents. In the "MAURITIUS" study, cummulative treatment doses up to 200 mCi (90)Y-DOTA-lanreotide were given as short-term infusion. Overall treatment results in 70 patients indicated stable tumor disease in 35% of patients and regressive tumor disease in 10% of tumor patients with different tumor entities expressing hSSTR. No acute or chronic severe hematological toxicity, change in renal or liver function parameters due to (90)Y-DOTA-lanreotide treatment, were reported. (90)Y-DOTA-DPhe(1)-Tyr(3)-octreotide may show a higher tumor uptake in neuroendocrine tumor lesions and may therefore be superior for treatment in patients with neuroendocrine tumors. However, there is only limited excess to long-term and survival data at present. Potential indications for (90Y-DOTA-lanreotide are radioiodine-negative thyroid cancer, hepatocellular cancer and lung cancer. Besides newer approaches and recent developments of 188)Re-labeled radioligands, no clinical results on the treatment response are yet available. In conclusion, several radioligands have been implemented on the basis of peptide receptor recognition throughout the last decade. A plentitude of preclinical data and clinical studies confirm their potential use in diagnosis as well as "proof-of-principle" for therapy of cancer patients. However, an optimal radiopeptide formulatioents. However, an optimal radiopeptide formulation does not yet exist for receptor-targeted radionuclide therapy. Ongoing developments may result in peptides more suitable for this kind of receptor-targeted radionuclide therapy.

Heterocyclic Compounds↗
PubMed2001

Characterization of (123)I-vascular endothelial growth factor-binding sites expressed on human tumour cells: possible implication for tumour scintigraphy.

To explore the possibility of vascular endothelial growth factor (VEGF) receptor scintigraphy of primary tumours and their metastases, we analysed the binding properties of (123)I-labelled VEGF(165) ((123)I-VEGF(165)) and (123)I-VEGF(121) to human umbilical vein endothelial cells (HUVECs), several human tumour cell lines (HMC-1, A431, KU812, U937, HEP-1, HEP-G2, HEP-3B and Raji), a variety of primary human tumours (n = 40) and some adjacent non-neoplastic tissues as well as normal human peripheral blood cells in vitro. Two classes of high-affinity (123)I-VEGF(165)-binding site were found on the cell surface of HUVECs. In contrast, one class of high-affinity binding sites for (123)I-VEGF(165) was found on HMC-1, A431, HEP-1, HEP-G2, HEP-3B and U937 cells as well as many primary tumours. For (123)I-VEGF(121), a single class of high-affinity binding site was found on certain cell lines (HUVEC, HEP-1 and HMC-1) and distinct primary tumours (primary melanomas, ductal breast cancers and ovarian carcinomas as well as meningiomas). Tumour cells expressed significantly higher numbers of VEGF receptors compared with normal peripheral blood cells and adjacent non-neoplastic tissues. Immunohistochemical staining revealed that the VEGF receptor Flk-1 is expressed to a much higher extent within malignant tissues compared with neighbouring non-neoplastic cells. We observed significantly greater specific binding of (123)I-VEGF(165) and (123)I-VEGF(121) to a variety of human tumour cells/tissues compared with the corresponding normal tissues or normal peripheral blood cells. In comparison with (123)I-VEGF(121), (123)I-VEGF(165) bound to a higher number of different tumour cell types with a higher capacity. Thus, (123)I-VEGF(165) may be a potentially useful tracer for in vivo imaging of solid tumours.

Animals↗
PubMed2001

Effects of vasoactive intestinal peptide (VIP) and somatostatin (SST) on lipoprotein receptor expression by A431 tumor cells.

A variety of tumor cells have been shown to express lipoprotein receptors. Recent data suggest that lipoprotein receptors may play a regulatory role in the growth of certain tumor cells. We investigated the effects of vasoactive intestinal peptide (VIP) and somatostatin-14 (SST-14) on the binding of 111Indium-labeled lipoproteins [(111)In-low density lipoprotein ((111)In-LDL), (111)In-high density lipoprotein ((111)In-HDL) and (111)In-very low density lipoprotein ((111)In-VLDL)] onto the epidermoid mammary carcinoma cell line A431. Scatchard analyses of the binding data indicated one class of specific high affinity binding sites for LDL, HDL and VLDL expressed by A431 cells, respectively. VIP increased significantly the binding capacity for (111)In-LDL on A431 cells. The VIP-induced increase of (111)In-LDL binding sites was inhibited by SST-14. Furthermore, SST-14 inhibited VIP-induced 3H-thymidine incorporation and adenosine 3'-5' cyclic monophosphate (cAMP) formation in A431 cells with IC50 values in the range of 5-7 nM. However, SST-14 showed no effect on dibutyryl-cAMP-induced increase of (111)In-LDL binding sites expressed on A431 cells. In contrast to (111)In-LDL binding, no effects of VIP or SST-14 on HDL or VLDL binding to A431 tumor cells were found. Our results suggest a direct effect of VIP and SST-14 on LDL-binding onto tumor cells. The complex interactions between VIP and SST-14 on LDL receptor expression of tumor cells may play a role in tumor cell lipid metabolism.

Bucladesine↗
PubMed2001

FDG-PET in adrenocortical carcinoma.

Adrenal cortical carcinoma (ACC) is a rare malignant neoplasm with a poor prognosis. Radical surgery of the primary tumor and of local as well as of distant recurrence is the only effective treatment, and requires accurate and early localization of recurrent tumors. In this regard, we prospectively scanned 10 patients with ACC, 8 during follow-up and 2 at primary work-up. In all patients PET scans from the neck to the upper thighs were obtained 45 minutes after injection of 370 MBq [18F]FDG. Reading was done visually, with the investigator blinded to the results of other diagnostic modalities. All known sites of ACC lesions showed markedly increased FDG uptake. In 3 patients, previously unknown lesions were identified by PET in the lung (one lesion), the abdomen (3 lesions), and the skeleton (multiple), respectively. One false positive liver focus was shown by PET aside from the true positive lung metastases in the same patient. The sensitivity/specificity of PET based on different organs was 100/97%, that based on the number of PET-detected lesions (N = 23) was 100/95%. PET altered or influenced the tumor stage in 3/10 patients, modifying the subsequent therapeutic management in 2/10 patients. We conclude that FDG-PET is highly useful in ACC and should be included in the work-up for initial staging as well as for follow-up.

Abdominal Neoplasms↗
PubMed2001

Comparative somatostatin receptor scintigraphy using in-111-DOTA-lanreotide and in-111-DOTA-Tyr3-octreotide versus F-18-FDG-PET for evaluation of somatostatin receptor-mediated radionuclide therapy.

BACKGROUND: Based on the high number of somatostatin (SST) receptors expressed by neuroendocrine tumors, long-acting SST analogs have been successfully used for tumor detection. New developments point to the potential use of these types of radioligands for tumor-specific radionuclide therapy. PATIENTS AND METHODS: We have comparatively investigated the diagnostic capacity of the SST analog. 111In-DOTA-lanreotide (LAN), as opposed to 111ln-DOTA-DPhe1-Tyr3-octreotide (TOCT) in tumor patients. This article gives an overview of recent scintigraphic results compared to CT/MRI, 18F-FDG-PET, endoscopy and/or surgery in a threshold of 218 tumor patients. RESULTS: As opposed to radiology, previously unknown tumor lesions were demonstrable by either SST radioligand in about one third of patients. In carcinoid patients, the SST scan sensitivity was 64% for LAN (18 of 28) and 87% (34 of 39) for TOCT, whereas the sensitivity was 100% in patients with (radioiodine-negative) thyroid cancer (17 of 17) for LAN and 95% for TOCT (20 of 21). Discordant scintigraphic results between LAN and TOCT (higher tumor uptake and/or visualisation of different lesions in the same patient) were also seen in patients with lymphoma, lung cancer and intestinal adenocarcinoma. In a direct comparison of both SST tracers in 38 tumor patients, LAN gave positive results in 35 of 38, TOCT in 36 of 38 and 18F-FDG-PET in 14 of 22 of the same patients. SST scan results obtained by both tracers were equivocal in 23 of 38 patients, but were better in 10 patients withTOCTand in 5 patients with LAN. CONCLUSIONS: We conclude that both SST radioligands are suitable tracers for tumor imaging, but may give significantly different uptake results for different tumor types. Since the uptake is most important for tumor therapy, using either longacting SSTanalogs, and/or 90Y-labeled analogs, careful evaluation should be made prior to therapy.

Adenocarcinoma↗
PubMed2001

FDG positron emission tomographic, radioiodine, and MIBI imaging in a patient with poorly differentiated insular thyroid carcinoma.

Poorly differentiated insular thyroid carcinoma is now classified as a separate entity among other tumors of the thyroid gland. Its histologic pattern and its clinical course are regarded as intermediate between well differentiated and anaplastic thyroid cancer. Insular carcinoma accumulates I-131, but no data exist regarding its fluorodeoxyglucose (FDG) positron emission tomographic (PET) uptake. The authors report F-18 FDG PET, Tc-99m MIBI, and radioiodine imaging features in a 63-year-old patient with metastatic insular thyroid carcinoma. After total thyroidectomy (for poorly differentiated insular carcinoma pT3a), the patient was referred for radioiodine ablation. No signs of recurrence were present until 16 months later, when thyroglobulin levels increased. An I-131 scan showed a single lesion in the right lung, and further radioiodine treatment was administered (cumulative dose [530 mCi], 19,610 MBq I-131). Three years after the initial diagnosis, FDG-PET and Tc-99m MIBI scans were performed within 5 days during thyroxine treatment. After that, thyroxine substitution was withdrawn; 6 weeks later, an I-131 whole-body scan was performed. Both radioiodine and MIBI images showed increased tracer uptake in the known lung lesion. However, FDG PET showed a normal tracer distribution. Magnetic resonance and computed tomographic imaging confirmed a 12-mm lesion in the right upper lobe. These findings support the concept of the "flip-flop phenomenon" in insular thyroid carcinoma, an alternating pattern of metastases with either I-131 or FDG-uptake. Despite poorly differentiated histologic findings, glucose metabolism was not increased in this patient with an insular tumor.

Carcinoma↗
PubMed2001

New trends in peptide receptor radioligands.

The high level expression of somatostatin receptors (SSTR) on various tumor cells has provided the molecular basis for successful use of radiolabeled octreotide/lanreotide analogs as tumor tracers in nuclear medicine. The vast majority of human tumors seem to overexpress the one or the other of five distinct hSSTR sub-type receptors. Whereas neuroendocrine tumors frequently overexpress hSSTR2, intestinal adenocarcinomas seem to over-express more often hSSTR3 or hSSTR4, or both of these hSSTR. In contrast to 111In-DTPA-DPhe1-octreotide (OCTREOSCAN) which binds to hSSTR2 and 5 with high affinity (Kd 0.1-5 nM), to hSSTR3 with moderate affinity (Kd 10-100 nM) and does not bind to hSSTR1 and hSSTR4, 111In/90Y-DOTA-lanreotide was found to bind to hSSTR2, 3, 4, and 5 with high affinity, and to hSSTR1 with lower affinity (Kd 200 nM). Based on its unique hSSTR binding profile, 111In-DOTA-lanreotide was suggested to be a potential radioligand for tumor diagnosis, and 90Y-DOTA-lanreotide suitable for receptor-mediated radionuclide therapy. As opposed to 111In-DTPA-DPhe1-octreotide and 111In-DOTA-DPhe1-Tyr3-octreotide, discrepancies in the scintigraphic results were seen in about one third of (neuroendocrine) tumor patients concerning both the tumor uptake as well as detection of tumor lesions. On a molecular level, these discrepancies seem to be based on a "higher" high-affinity binding of 111In-DOTA-DPhe1-Tyr3-octreotide to hSSTR2. Other somatostatin analogs with divergent affinity to the five known hSSTR subtype receptors have also found their way into the clinics, including 99mTc-HYNIC-octreotide or 99mTc-depreotide (NEOSPECT; NEOTECT). Most of the imaging results are reported for neuroendocrine tumors (octreotide analogs) or non-small cell lung cancer (99mTc-depreotide), indicating high diagnostic capability of this type of receptor tracers. Consequently to their use as receptor imaging agents, hSSTR recognizing radioligands have also been implemented for experimental receptor-targeted radionuclide therapy. The study "MAURITIUS" (MulticenterAnalysis of a Universal Receptor Imaging and Treatment Initiative, a eUropean Study), a Phase IIa study, showed in patients with a calculated tumor dose >10 Gy/GBq 90Y-DOTA-lanreotide, the proof-of-principle for treating tumor patients with receptor imaging agents. Overall treatment results in >60 patients indicated stable tumor disease in roughly 35% of patients and regressive disease in 15% of tumor patients with different tumor entities. No acute or chronic severe hematological toxicity, change in renal or liver function parameters due to 90Y-DOTA-lanreotide, was reported. 90In-DOTA-DPhe1-Tyr3-octreotide may show a higher tumor uptake in neuroendocrine tumor lesions and may therefore provide even better treatment results in tumor patients, but there is only limited excess to long-term and survival data at present. Besides newer approaches and recent developments of 188Re-labeled radioligands no clinical results on the treatment response is available yet. In conclusion, several radioligands have been implemented on the basis of peptide receptor recognition throughout the last decade. A plentitude of preclinical data and clinical studies confirm "proof-of-principle" for their use in diagnosis as well as therapy of cancer patients. However, an optimal radiopeptide formulation does not yet exist for receptor-targeted radionuclide therapy.

Animals↗
PubMed2001

111In-DOTA-lanreotide scintigraphy in patients with tumors of the lung.

UNLABELLED: Imaging with radiolabeled somatostatin (SST) analogs has recently been established for the localization of various human SST receptor (hsstr)-positive tumors, including neuroendocrine tumors, lymphomas, and non-small cell lung cancer (NSCLC). METHODS: 111In-1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid-lanreotide (DOTA-LAN) scintigraphy (150 MBq; 7 nmol per patient) was performed on 47 patients (28 patients with primary tumors, 19 patients with lung metastases from other tumors) to evaluate the tumor binding in patients with histologically confirmed lung cancer. A group of 27 tumor patients without documented lung lesions served as the control group. Early and delayed planar and SPECT images were acquired. Whole-body scintigraphy was performed at 0.5, 4-6, 24, and 48 h after injection for tumor dose estimation. In addition, hsstr subtype expression and radioligand binding characteristics were studied in vitro using lung tumor samples (n = 15). RESULTS: 111In-DOTA-LAN indicated the primary lung tumor in 16 of 16 NSCLC patients. Lymph node metastases were visualized in 6 of 6 NSCLC patients, and bone metastases were seen in 3 of 3 NSCLC patients. 111In-DOTA-LAN scintigraphy indicated lung carcinoid in 5 of 5 patients and small cell lung cancer lesions in 6 of 6 patients. Multiple lung metastases were shown in all 6 patients with non-Hodgkin's lymphoma and in the 1 patient with Hodgkin's disease, 5 of 5 colorectal adenocarcinoma patients, 4 of 4 carcinoid patients, 2 of 2 neuroendocrine carcinoma (NEC) patients, and 1 of 1 angiosarcoma patient. Pulmonary tumor sites not indicated by CT or MRI were visualized in 6 of 47 tumor patients (i.e., 13%; lung metastases in 1 carcinoid patient and 1 NEC patient, lymph node metastases in 1 carcinoid patient and 2 NSCLC patients, bone metastases in 1 carcinoid patient). The estimated lung tumor dose ranged between 0.2 and 5 mGy/MBq. Focal lung uptake of 111In-DOTA-LAN was not observed in any of the 27 control patients. In vitro binding studies indicated high-affinity binding sites for 111In-DOTA-LAN in NSCLC samples (dissociation constants, 0.5 and 4 nmol/L) with predominant expression of hsstr4. CONCLUSION: 111In-DOTA-LAN yields high tumor binding for various human lung tumors. Consecutively, radiopeptide therapy may offer a potential new treatment alternative for some lung tumor patients.

Case-Control Studies↗
PubMed2001

Effects of chemotherapeutic agents on expression of somatostatin receptors in pancreatic tumor cells.

UNLABELLED: Specific tumors express high amounts of receptors for somatostatin (SST), providing the basis for imaging and treatment using radiolabeled SST analogs. However, little is known about the potential influence of cytotoxic drugs on SST receptor (SSTR) expression in malignant cells. METHODS: To study the interaction between cytotoxic drugs and SSTR expression, the pancreatic cancer-derived tumor cell lines BxPC-3, Panc-1, Capan-1, and ASPC-1 were exposed to a range of cytotoxic drugs in vitro: Gemcitabine, 5-fluorouracil, cisplatin (cis-diaminedichloroplatinum [II]), camptothecin, mitomycin C, and doxorubicin were checked for changes in binding characteristics of the SSTR ligand (111)In-1,4,7,10-tetraazacyclododecane- N,N',N",N"'-tetraacetic acid-lanreotide (DOTA-LAN). Chemosensitivity was quantitated by measurements of reduction in cell numbers, changes in cell cycle distribution, and appearance of apoptotic subG1 (subG1/0 cell DNA content) cells. RESULTS: Cells were treated with gemcitabine (1.0 or 2.0 microg/mL), 5-fluorouracil (65-520 microg/mL), camptothecin (1.5 or 3 microg/mL), mitomycin C (0.1 or 0.2 microg/mL), and doxorubicin (1.0 or 2.0 microg/mL). Each of the chemotherapeutic agents induced a loss of high-affinity receptors. In addition, gemcitabine caused a reduction of low-affinity receptors in BxPC-3, Panc-1, and ASPC-1 cells. Mitomycin C, camptothecin, and 5-fluorouracil also induced an overexpression of low-affinity receptors. In cells pretreated with cisplatin (2-10 microg/mL), binding of DOTA-LAN was increased. Excluding gemcitabine, the increase in low-affinity binding sites exhibits a weak correlation with apoptosis (r(2) = 0.62). For gemcitabine, these effects were reversed after 4 d of recovery of the cell lines, eventually revealing overexpression of low- and high-affinity sites for BxPC-3 and Panc-1 cells and low-affinity sites for ASPC-1 cells. CONCLUSION: Our results clearly show that the pancreatic tumor lines reduce the expression of high-affinity DOTA-LAN binding sites during application of chemotherapeutic drugs, which is accompanied by variable overexpression of low-affinity binding sites. In the case of gemcitabine, SSTRs are overexpressed during recovery from drug exposure within 4 d. These findings may have implications on the interpretation of scintigraphic results obtained by receptor ligands.

Adenocarcinoma↗
PubMed2000

18F-fluorodeoxyglucose (FDG)-PET features of focal nodular hyperplasia (FNH) of the liver.

AIM: The aim of this paper is to describe the imaging pattern of focal nodular hyperplasia (FNH) by l8F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). METHODS: Eight consecutive asymptomatic patients with histologic proof of FNH underwent 18F-FDG PET imaging. The lesions were found incidentally. The 18F-FDG PET imaging was performed with a dedicated PET tomograph after intravenous injection of 300-370 MBq 18F-FDG. The 18F-FDG accumulation in the lesions was (semi)quantified by calculating the standardized uptake value (SUV) and SUV has been corrected for the lean body mass (LBM). Eight patients with liver metastases spread from melanoma (n=2) and colorectal carcinoma (n=6) served as controls. The size of the FNH lesions and of the control group ranged from 2.0 to 8.5 cm (mean 4.83 cm +/- 2.37) and from 1.5 to 6 cm (mean 3.28 +/- 1.52), respectively. RESULTS: While in malignant liver lesions the accumulation of 18F-FDG was significantly increased, all FNH lesions showed normal or even decreased accumulation of 18F-FDG. In FNH lesions, SUV ranged between 1.5 and 2.6 (mean 2.12 +/- 0.38), whereas all liver metastases showed an increased SUV ranging between 6.20 and 16.00 (mean 10.07 +/- 3.79). The SUV corrected for LMB (SUVLBM) was similar to the SUV and ranged between 0.9 and 2.2 (mean 1.81 +/- 0.41) for FNH and between 5.9 and 16.3 (mean 9.15 +/- 4.03), respectively. CONCLUSION: In contrast to liver metastases, there is no increased glucose metabolism in FNH in vivo. The imaging feature of FNH by 18F-FDG-PET imaging is not specific for FNH; however, it may be helpful to differentiate FNH from liver metastases in cancer patients if radiological methods are not diagnostic.

Adult↗