Search

A 76-year-old man with bone metastases of prostate cancer diagnosed a year ago was admitted for relief of bone pain (visual analogue scale: 90%) most markedly in cervical spine and upper extremities due to skeletal metastases. His serum prostate specific antigen level was markedly increased (351 ng/ml). After documentation of sufficient tracer uptake in multiple bone metastases on whole-body 99mTc-MDP bone scan, we treated him with a single intravenous injection of 2.4 GBq 188Re-HEDP. Quality control of 188Re-HEDP was performed with TLC within 30 min prior to injection, radiochemical purity was >95%, free rhenium and colloid ratios were less than 3%. For pain, he was taking Novalgin 30 drops t.i.d. and used Fentanyl patch 50 g/72 h. Fig. 1 shows increased activity localization in multiple bone metastases and the liver lesion after treatment with 188Re-HEDP, as well as on the whole-body scans obtained a week prior to treatment. This metastatic liver lesion was diagnosed on a conventional CT scan 6 months before treatment. The SPECT/CT study (obtained at 24 h after injection) shows tracer accumulation in the liver lesion, in abdominal lymph nodes (in the hepatoduodenal ligament) and in stomach (Fig. 2A and B). An abdominal section of the SPECT/CT study shows that the area of activity localization on right side of abdomen on whole body image corresponds to intestinal contents (Fig. 2C). Liver metastases of various malignant tumors such as breast cancer have been reported to show accumulation on bone scintigraphy with 99mTc-MDP. Limouris and Skukla reported 186Re-HEDP uptake in the stomach in two patients with osseous metastases because of prostate and breast cancer1; however, we could not find any reports on visualization of lymph node metastases on posttherapy scan after administration of 188Re-HEDP. Accumulation of

In a patient with the occipitoparietal form of Creutzfeldt-Jakob disease (CJD) (Heidenhain type) positron emission tomography (PET) demonstrated decreased glucose utilization in the occipital lobes and adjacent cortical regions. Single photon emission computed tomography (SPECT) with 99mTc-bicisate showed a "coupled" decrease in blood flow in identical cortical areas in this patient. In contrast, magnetic resonance imaging (MRI) was normal. In the early stage of CJD, when still no major morphological abnormalities can be observed, functional imaging is useful for differential diagnosis, particularly to exclude other causes of dementia or pathological EEG patterns.

The therapeutic potential of the somatostatin analogue RC-160 radiolabeled with 188 Re was evaluated in nude mice bearing xenografts of human prostate adenocarcinoma. 188 Re-RC-160 was selectively retained in both DU-145 and PC-3 tumors following direct intra-tumor injection at all time points examined (2, 6 and 24 hr post-injection). Unbound 188 Re-RC-160 was rapidly excreted via the hepatobiliary system and, with the exception of the gastrointestinal tract, very little normal organ uptake was found at any time point examined. Negative control compounds, 188 Re-perrhenate and 188 Re-mercaptoacetyl-triglycine ( 188 Re-MAG3), were essentially washed out of the tumor by 6 hr post-injection and were rapidly excreted through the kidneys. 131 I-RC-160, used as a reference compound, had a biodistribution in tumor-bearing animals similar to that of 188 Re-RC-160. In PC-3 xenografts, 188 Re-RC-160 gave a dose-dependent therapeutic response (stasis or regression) even in animals with relatively large tumor masses (greater than 600 mm 3 ), whereas the macro-aggregated form of 188 Re-RC-160 did not. Long-term studies with 188 Re-RC-160 demonstrated a protracted reduction of tumor volume and a positive effect on animal survival. Neither RC-160 by itself nor a 188 Re-labeled peptide, unrelated to somatostatin (PA-22-2, a laminin peptide), demonstrated the reduction in tumor mass observed with 188 Re-RC-160. 188 Re-RC-160 shows potential as a new clinical agent for treatment of somatostatin-receptor-positive cancers.

We examined the potential of radiolabeled somatostatin analogs, 125I-Tyr-3-octreotide (125I-octreotide), (111)In-DTPA(diethylenetriaminepentaacetatic acid)-D-Phe-1-octreotide (111In-octreotide), and 188Re-octreotide for targeting small-cell lung cancer (SCLC) in a mouse model. Tyr-3-octreotide was labeled with 125I by the chloramine T method, and (111)In-octreotide was obtained as a kit, while 188Re was eluted from a 188W/188Re generator, and octreotide was directly labeled with 188Re by reducing disulfide bonds. The 125I-, 111In-, and 188Re-octreotides were injected i.v. into athymic mice bearing NCI-H69 tumors, and the biodistributions were determined at 15 min, and 2, 4, 8, and 24 h. Tumor uptakes were 0.5+/-0.2, 0.3+/-0.1, 0.3+/-0.1 %ID/g, and tumor-to-blood ratios were 1.8, 11.9, 1.2 at 8 h for 125I-, 111In-, and 188Re-octreotides, respectively. Accumulations of 111In-octreotide in normal tissues were lower than those of 125I- and 188Re-octreotides. 188Re-octreotide can be used to localize SCLC lesions as efficiently as radioiodinated octreotide. However, 111In-octreotide was the most suitable agent to obtain high tumor-to-normal tissue contrast for localizing SCLC.

Temporal lobe dysfunction has been postulated in affective disorders by different brain imaging techniques. To further elucidate the possible relationship between electrophysiological variables in rapid cycling mood disorders (RCMD) and temporal lobe dysfunction we firstly recorded sphenoidal EEGs in addition to surface EEGs and 99m Tc-HMPAO-SPECT in three patients with RCMD. As compared to surface recordings the sphenoidal electrodes record more specifically the electrical activity arising within the mesio-basal temporal lobe. The preliminary results indicate that there is a dysrhythmia and/or rhythmic delta activity in RCMD which was predominantly apparent in the left temporo-mesial region in two cases. Furthermore, there was a hypoperfusion in the left temporal and temporo-parietal region using 99m Tc-HMPAO-SPECT technique in two patients, respectively. This pilot study suggests that temporal lobe structures might be of particular relevance in RCMD and thus provides further evidence suggestive of temporal lobe involvement in affective disorders. Our findings indicate that electrophysiological recordings and brain imaging techniques could be helpful in further elucidating the pathophysiology underlying rapid cycling mood disorders.

Peptide receptor radionuclide therapy is an effective treatment option for patients with well-differentiated somatostatin receptor-expressing neuroendocrine tumors. However, published data result mainly from retrospective monocentric studies. We initiated a multi-institutional, prospective, board-reviewed registry for patients treated with peptide receptor radionuclide therapy in Germany in 2009. In five centers, 297 patients were registered. Primary tumors were mainly derived from pancreas (117/297) and small intestine (80/297), whereas 56 were of unknown primary. Most tumors were well differentiated with median Ki67 proliferation rate of 5% (range 0.9-70%). Peptide receptor radionuclide therapy was performed using mainly yttrium-90 and/or lutetium-177 as radionuclides in 1-8 cycles. Mean overall survival was estimated at 213 months with follow-up between 1 and 230 months after initial diagnosis, and 87 months with follow-up between 1 and 92 months after start of peptide receptor radionuclide therapy. Median overall survival was not yet reached. Subgroup analysis demonstrated that best results were obtained in neuroendocrine tumors with proliferation rate below 20%. Our results indicate that peptide receptor radionuclide therapy is an effective treatment for well- and moderately differentiated neuroendocrine tumors irrespective of previous therapies and should be regarded as one of the primary treatment options for patients with somatostatin receptor-expressing neuroendocrine tumors.

Peptide receptor radionuclide therapy is an effective treatment option for patients with well-differentiated somatostatin receptor-expressing neuroendocrine tumors. However, published data result mainly from retrospective monocentric studies. We initiated a multi-institutional, prospective, board-reviewed registry for patients treated with peptide receptor radionuclide therapy in Germany in 2009. In five centers, 297 patients were registered. Primary tumors were mainly derived from pancreas (117/297) and small intestine (80/297), whereas 56 were of unknown primary. Most tumors were well differentiated with median Ki67 proliferation rate of 5% (range 0.9–70%). Peptide receptor radionuclide therapy was performed using mainly yttrium-90 and/or lutetium-177 as radionuclides in 1–8 cycles. Mean overall survival was estimated at 213 months with follow-up between 1 and 230 months after initial diagnosis, and 87 months with follow-up between 1 and 92 months after start of peptide receptor radionuclide therapy. Median overall survival was not yet reached. Subgroup analysis demonstrated that best results were obtained in neuroendocrine tumors with proliferation rate below 20%. Our results indicate that peptide receptor radionuclide therapy is an effective treatment for well- and moderately differentiated neuroendocrine tumors irrespective of previous therapies and should be regarded as one of the primary treatment options for patients with somatostatin receptor-expressing neuroendocrine tumors.

Therapy in nuclear medicine practice has a long distinguished history. Nuclear medicine therapy is required to be highly specific and targeted, since it always involves administration of unsealed sources of radioactivity. Most therapy agents utilize s-particle emissions for their ability to penetrate tissues. This deposition of energy in tissue by s emitters results in cellular damage. Among the s emitters there are several choices with respect to energy of the s emission. Lower energy s particles can travel a few cell diameters, or at most in the sub-millimeter range. Higher energy s particles such as those emitted by Y90 have an excellent tissue penetration with a range beyond the source of several millimeters. The physical half-life of the therapeutic radionuclide is an important consideration and underlying principle for therapy planning. Rarely, except in thyroid treatment, is the simple salt form of the radionuclide used. It is most likely attached to a drug or particle that controls its biodistribution. The ideal therapeutic radiopharmaceutical is one that remains attached to the parent drug or its metabolites, and is excreted rapidly through a known simple route1.

131I-MIBG therapy for neuroendocrine tumours may be dose limited. The common range of applied cumulative activities is 10-40 GBq. We report the uneventful cumulative administration of 111 GBq (= 3 Ci) 131I-MIBG in a patient with metastatic paraganglioma. Ten courses of 131I-MIBG therapy were given within six years, accomplishing symptomatic, hormonal and tumour responses with no serious adverse effects. Chemotherapy with cisplatin/vinblastine/dacarbazine was the final treatment modality with temporary control of disease, but eventually the patient died of progression. The observed cumulative activity of 131I-MIBG represents the highest value reported to our knowledge, and even though 12.6 GBq of 90Y-DOTATOC were added intermediately, no associated relevant bone marrow, hepatic or other toxicity were observed. In an individual attempt to palliate metastatic disease high cumulative activity alone should not preclude the patient from repeat treatment.

Many solid malignant tumors, mainly prostate, breast, and lung cancer, generate bone metastases throughout the course of disease. They can lead to serious complications of which chronic pain syndrome is the most important and frequent one, having a negative impact on quality of life and the social environment of the patient. Radionuclide therapy of bone metastases was introduced decades ago as a therapeutic option for patients suffering from painful bone metastases. Out of several radiopharmaceuticals, which are or have been used for this purpose, Rhenium-188 hydroxyethylidene diphosphonate (Re-188 HEDP) is a relatively new and, mainly because of its physical properties, attractive alternative. It localizes in skeletal metastases and emits beta particles and was previously shown to be beneficial for the palliative treatment of metastatic bone disease. In this chapter, the methodology of Re-188 HEDP treatment as well as clinical studies and new treatment strategies involving Re-188 HEDP are discussed in order to provide a detailed overview of this treatment option for patients suffering from bone metastases.

Peptide receptor radionuclide therapy (PRRT) is an efficient treatment for gastroenteropancreatic neuroendocrine tumors (GEP NETs), with outstanding overall response rates and survival. However, little is known about the particular efficacy regarding bone metastasis (BM). Methods: We retrospectively analyzed a consecutive subgroup of 42 patients with BM of GEP NETs treated with PRRT (177Lu-octreotate, 4 intended cycles at 3 monthly intervals [10–14 wk]; mean activity per cycle, 8.1 GBq). Availability of restaging and outcome data was required for patient inclusion. Baseline characteristics, including age, tumor origin, performance score, Ki-67 index, tumor load, tumor uptake, plasma chromogranin A, and neuron-specific enolase, were analyzed regarding impact on tumor regression (modified M.D. Anderson criteria) and time to progression. Survival analyses were performed using Kaplan–Meier curves, log-rank test at a significance level of P less than 0.05, and Cox proportional hazards model for uni- and multivariate analyses. Results: Median follow-up was 32 mo. The observed response of BMs consisted of complete remission in 2 (4.8%), partial remission in 14 (33.3%), minor response in 5 (11.9%), stable disease in 16 (38.1%), and progressive disease in 5 (11.9%) patients. Median progression-free survival and overall survival (OS) were 35 mo (26–44, 95% confidence interval) and 51 mo (37–65, 95% confidence interval), respectively. Patients with responding BMs (complete remission, partial remission, or minor response) exhibited a trend toward better OS (median OS not reached after 53 mo) when compared to nonresponding patients (39 mo, P = 0.076). Only Ki-67 index (>10%) and chromogranin A level (>600 ng/mL) contributed to regression analysis. Conclusion: BM of GEP NETs is effectively controlled by PRRT, with long progression-free survival and OS. Poor patient condition and multifocality of BMs do not clearly affect treatment efficacy, possibly encouraging the use of PRRT in advanced bone metastatic disease. Larger studies are needed to assess predictors of treatment outcome in these patients.

The prognosis of patients with surgically unresectable differentiated thyroid tumors deteriorates significantly if radioiodine therapy is or becomes ineffective, considering the limited role of conventional chemotherapies in these patients. Several alternative approaches have been investigated for the treatment of patients with advanced thyroid malignancies in recent years. Among targeted therapies, tyrosine kinase inhibitors have resulted in the most encouraging responses and could soon be, along with redifferentiation therapy, the possible palliative strategies. Radiopeptide therapy, especially with beta emitter-labeled DOTANOC, which shows a great affinity to the somatostatin receptors expressed by thyroid tumor cells, might also be an attractive approach considering its comparatively low rate of side effects. However, the indication should be evaluated on individual basis. Medullary thyroid carcinoma shows a worse overall prognosis compared with the other differentiated thyroid tumors especially because of its natural resistance to radioiodine therapy. However, among possible palliative strategies, 131 I-meta-iodobenzylguanidine therapy is a noteworthy therapeutic approach in patients experiencing metastasized medullary thyroid carcinoma. In summary, recent developments in the treatment of patients with advanced thyroid malignancies have shown promising results, raising the hope for better outcomes in these patients in future.

While influx of chemoembolic agents into the hepatic falciform artery (HFA) from the hepatic artery can cause supraumbilical skin rash, epigastric pain and even skin necrosis, the significance of a patent HFA in patients undergoing radioembolization is not completely clear. Furthermore, the presence of tracer in the anterior abdominal wall seen in (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) images, which is generally performed prior to radioembolization, has been described as a sign of a patent HFA. The aim of this retrospective study was to evaluate the incidence and consequences of (99m)Tc-MAA accumulation in the anterior abdominal wall, indicating a patent HFA, in patients undergoing radioembolization of liver tumours.A total of 224 diagnostic hepatic angiograms combined with (99m)Tc-MAA SPECT/CT were acquired in 192 patients with different types of cancer, of whom 142 were treated with a total of 214 radioembolization procedures. All patients received a whole-body scan, and planar and SPECT/CT scans of the abdomen. Only patients with extrahepatic (99m)Tc-MAA accumulation in the anterior abdominal wall were included in this study. Posttreatment bremsstrahlung SPECT/CT and follow-up results for at least 3 months served as reference standards.Tracer accumulation in the anterior abdominal wall was present in pretreatment (99m)Tc-MAA SPECT/CT images of 18 patients (9.3%). The HFA was found and embolized by radiologists before treatment in one patient. In the remaining patients radioembolization was performed without any modification in the treatment plan despite the previously mentioned extrahepatic accumulation. Only one patient experienced abdominal muscle pain above the navel, which started 24 h after treatment and lasted for 48 h without any skin changes. The remaining patients did not experience any relevant side effects during the follow-up period.Side effects after radioembolization in patients with tracer accumulation in the anterior abdominal wall on (99m)Tc-MAA scans indicating a patent HFA are neither common nor severe. Thus, there is no absolute need for prophylactic embolization of the HFA or modification of the treatment plan if the HFA is not detectable on angiography.

Background : Squamous cell carcinoma of the head and neck frequently spreads to regional lymph nodes in early stages. While radioimmunoimaging has progressed to a rather routine diag

First results of tumor imaging using radiolabelled antibodies date back to 1953. During the last 40 years an improvement of this diagnostic procedure was achieved by the use of monoclonal antibodies a

The role of the Ki-67 tumour proliferation index (PI) in predicting the efficacy of peptide receptor radionuclide therapy (PRRT) in gastroenteropancreatic tumours (GEP-NET) remains undetermined. This single-centre analysis focused on the potential therapeutic impact of this immunohistochemical parameter.A total of 81 consecutive GEP-NET patients treated with (177)Lu-DOTA-octreotate (mean activity of 7.9 GBq per cycle, usually four treatment cycles at standard intervals of 3 months) were retrospectively analysed. Both an evaluable PI and tumour response (modified SWOG criteria) were required for patient inclusion.Response of tumours with a PI of ≤20% (partial response 40%, minor response 15%, stable disease 34%, progressive disease 11%) was comparable in all PI subsets, including those with a PI of 20%. However, G3 tumours (PI 20%) showed progression in 71% of patients.Response to PRRT is consistent over the PI range of ≤20% (G1 + G2). Contrary to preliminary previous suggestions, a PI of 15% or 20% should not preclude candidates from somatostatin receptor-targeted radiotherapy.

Radioembolization (RE), also termed selective internal radiation therapy (SIRT), has been gradually introduced to the clinical arsenal of cytoreductive modalities in recent years. There is growing evidence for efficiency in liver tumors of various entities, with the most prominent ones being hepatocellular carcinoma, colorectal cancer, and neuroendocrine tumors. Hepatic metastases of numerous other tumor entities including breast cancer, cholangiocarcinoma, and pancreatic cancer are treatment-sensitive, even when being refractory to other treatment modalities such as bland-embolization, regional, or systemic chemotherapy. The antitumor effect of SIRT is related to radiation rather than embolization, with extraordinary high local radiation doses obtained selectively at the site of viable tumor and little affection of the surrounding normal liver tissue. Morphologic changes after RE may pose difficulties for interpretation in conventional restaging with regard to tumor viability and true response to treatment. Therefore, functional imaging, that is, metabolic imaging with 18 F fluorodeoxyglucose positron emission tomography (computed tomography) in the majority of treated tumors, is regarded the gold standard in this respect and should be included for pre- and post-SIRT assessment. To prevent serious toxicity to be associated with the potent antitumor efficacy, meticulous pretreatment evaluation is of particular importance. Improvements in predicting dosimetry will help optimize treatment and patient selection. Nuclear medicine procedures are essential for planning, performing, and monitoring of RE. However, the interdisciplinary aspect of patient management has to be emphasized for this particular treatment form. As SIRT is moving forward from the salvage setting indication to the use in earlier stages of hepatic tumor disease and with the advent of new treatment protocols and targeted therapies, embedding SIRT into a multidisciplinary approach will become even more important. This article focuses on procedural and technical aspects for selection, preparation, and performance of treatment as well as post-therapeutic monitoring and response assessment.

Ziel der vorliegenden Studie war, einen moglichen Einfluss des weiblichen Geschlechts auf das Ausmas moglicher myokardialer Perfusionsdefekte in der 99mTc-sestamibi-Myokardperfusions-Szintigraphie (MPS) und auf neu auftretende kardiale Ereignisse (KE) bei Patienten mit einem Alter ≥ 70 Jahre zu erfassen. 86 Patienten ≥ 70 Jahre (74,4 ± 3,2 Jahre; Frauen: n = 46; 53,5%) mit Verdacht auf oder bekannter KHK, die mit einer MPS untersucht wurden, wurden in die Studie eingeschlossen. Eine semiquantitative Analyse der MPS wurde durchgefuhrt und die Summed Stress (SSS), Summed Difference (SDS) und Summed Rest Scores (SRS) berechnet. Kardiale Ereignisse umfassten Myokardrevaskularisation und -infarkt und Herztod. Eine multivariate Regressionanalyse wurde durchgefuhrt, um einen moglichen unabhangigen Einfluss verschiedener patientenbezogener Variablen auf die Ergebnisse der MPS zu ermitteln. Kaplan-Meier- und Log-rank- Analysen wurden berechnet, um das KE-freie Uberleben in Relation zum Geschlecht zu erfassen. Normale SSS (87,0% vs. 27,5%; p < 0,0001), SDS (80,4% vs. 27,5%; p < 0,0001) und SRS (97,8% vs. 82,5%; p = 0,023) wurden signifikant haufiger bei Frauen gefunden, wahrend die Inzidenz mild und ausgepragt pathologischer SSS (6,5% vs. 35%; p = 0,001 bzw. 2,2% vs. 25%; p = 0,002) und SDS (15,2% vs. 52,5%; p < 0,0001 bzw. 2,2% vs. 17,5%; p = 0,023) signifikant hoher fur Manner war. Die multivariate Regressionsanalyse zeigte weibliches Geschlecht als unabhangigen Pradiktor fur normale SSS- (Odds ratio/OR: 17,6) und SDS-Werte (OR: 53,3). Im Vergleich zu Mannern war das weibliche Geschlecht mit einem signifikant hoheren Herztod-freien Uberleben assoziiert (p = 0,031). Weibliches Geschlecht zeigt eine unabhangige Assoziation mit einem signifikant niedrigeren Ausmas pathologischer MPS-Ergebnisse und einem hoheren Herztod-freien Uberleben bei alteren Patienten.

In this case we show the significance of dual time point PET in determining the nature of an abdominal process in a 67-year-old man with a newly diagnosed adenocarcinoma of the esophagus. Whole body PET/CT detected abnormal uptake in the distal part of the esophagus. In addition, focally increased FDG uptake was detected in the right abdomen. The late PET images of the abdomen showed an increase in the SUV resulting in this lesion being evaluated as malignant. The final pathology of the abdominal mass revealed a follicular B-Cell non-Hodgkin lymphoma grade I.

SummaryThere is little data regarding the impact of subclinical hyperthyroidism on coagulation metabolism in patients undergoing systemic anticoagulation therapy with coumarin derivates. In this retrospective analysis we studied 233 patients with benign thyroid disorders receiving therapeutic iodine-131, as well as concomitant systemic anticoagulation therapy (subclinical hyperthyroidism: n=178; overt hyperthyroidism: n=15; euthyroidism: n=40). Multivariate regression analyses were performed in the total study population as well as in the subgroup of patients with subclinical hyperthyroidism to identify the possible impact of several variables on anticoagulation therapy, large enough to push the International Normalized Ratio (INR) level out of the therapeutic range (INR 3.0).Therapy with antibiotics or nitrates was significantly associated with INR-values >3.0 in the total population, while ACE inhibitors were associated with lower incidence of INR-values 3.0, whereas therapy with thyroid suppressive drugs or TSH-values

Treatment of malignant pleural or peritoneal effusions is one of the “oldest” therapies using radioactive isotopes and was first described by J.H. Muller more than 50 years ago (Muller 1945)

Medulloblastoma (MB) is a primitive neuroectodermal tumour constituting a grade IV brain malignancy. Early and correct detection of recurrence or metastasis is desirable for follow-up of patients in this entity. Frequent expression of somatostatin receptors by MB lesions facilitates functional tumour imaging by somatostatin receptor scintigraphy (SRS). To investigate the value of SRS in the follow-up of MB, the results of ten consecutive patients (seven children and three adults) undergoing additional imaging with 111In-pentetreotide were reviewed. Four, 24 and 48 h p.i. planar and whole body images as well as a SPECT study at 4 h p.i. were acquired after intravenous injection of 109 +/- 35 MBq 111In-pentetreotide (Octreoscan). SRS yielded 11 positive and ten negative imaging results, compared to 17 positive and four negative in magnetic resonance imaging (MRI). The lesion-by-lesion analysis with a total of 44 lesions revealed a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 42%, 83%, 94%, 18% for SRS and 89.5%, 50%, 92%, 43% for MRI. Based on a per-patient analysis, considering the patient as to be either tumour-free or tumour-positive by one imaging modality, the following values for sensitivity, specificity, PPV and NPV were obtained: 61%, 100%, 100%, 30% for SRS and 94%, 67%, 94%, 67% for MRI. MRI remains the first step imaging technique in medulloblastoma patients before and after surgery and during the follow-up providing the highest sensitivity. However, to improve specificity and contribute to correct diagnosis in MB 111In-pentetreotide scintigraphy should be considered as a confirmatory second step imaging tool, especially in case of equivocal MRI results. Moreover, a positive SRS scan might serve as a reference before and after somatostatin receptor targeted radiotherapy.

Diagnosis of prostate cancer (PC) still remains critical as non-invasive screening with prostate specific-antigen (PSA) lacks to indicate malignancy of the prostate in some cases. Recent research has shown that clinically meaningful PC can develop in patients with a PSA value4 ng/ml, frequently defined as upper limit of normal serum PSA levels. Furthermore, both morphological (computed tomography (CT), magnetic resonance imaging, transrectal ultrasound) and functional imaging with (18)fluorodeoxyglucose positron emission tomography (FDG-PET) are associated with several limitations for primary diagnosis of PC. We report a case of an incidentally diagnosed PSA-negative PC by (18)FDG PET/CT in a patient with a previous diagnosis of a hypopharyngeal cancer.

A 61-year-old man presented with spontaneous pneumothorax. After diagnosis of emphysemic bullae, the patient underwent talc pleurodesis and had no further complaints. Five years later a routine chest X-ray showed suspicious pleural lesions in addition to the emphysema, which was deemed compatible with the known history of talc pleurodesis. Subsequent chest CT, however, revealed one lesion in the right lung that appeared not typical for this condition in addition to multiple lesions in pleural proximity. FDG-PET/CT demonstrated high glucose uptake in all the lesions. Subsequent needle biopsy of the suspicious intrapulmonary and also of one mediastinal lesion yielded the histopathological diagnosis of talcum granuloma with long-standing calculous fibrotic changes and no evidence of malignancy. This report on PET/CT after talc pleurodesis addresses the potential pitfalls caused by this condition, as chronic granulomatous reactions, like other inflammatory lesions, may account for highly increased FDG uptake which should be interpreted with caution and not simply read as a sign of malignancy. PET/CT offers the opportunity to exactly localize the areas of increased FDG uptake within regions of pleural thickening caused by talc deposition, however, the dilemma of misleading FDG accumulation cannot be solved by this hybrid imaging modality.

Background As single-head data acquisition for thallium-201 myocardial SPECT is a frequently used method mainly in the outpatient medical care as well as in smaller hospitals, comparison to dual-head data collection is a still discussed issue mainly with regard to quality control and -assurance. Methods A total of 1334 patients undergoing thallium-201 myocardial SPECT for diagnosis of myocardial ischemia and/or viability have been retrospectively analyzed. In 554 patients, a single-head gamma camera (360° rotation) has been applied, whereas a dual-head gamma camera (180° rotation) has been used in 780 patients. Four hundred twenty-six patients received both myocardial SPECT as well as coronary angiography. The diagnostic value of both applied acquisition techniques has been analyzed. Results Regarding myocardial viability, positive predictive value for the diagnosis of myocardial scar tissue was significantly higher for dual-head- as compared to single-head acquisition. Among the 426 patients undergoing diagnosis of myocardial ischemia, significant differences have only been found with regard to specificity being higher in the single-head acquisition. Diagnosis of myocardial ischemia related to a distinct myocardial perfusion region showed a significantly higher sensitivity of dual-head acquisition for the left anterior descending perfusion area, whereas specificity was significantly higher for single-head acquisition. Conclusions Our results indicate a beneficial effect of dual-head data collection with regard to sensitivity of the diagnosis of myocardial ischemia. In contrast, single-head data acquisition was superior with regard to specificity. However, it is justified to preferably apply dual-head data collection in clinical routine due to the shorter acquisition time leading to an evident time benefit of this acquisition technique.

Radiolabeled octreotide analogs (Oct) and metaiodobenzylguanidine (MIBG) offer 2 different approaches for imaging and targeting metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NET). Despite successful establishment of the revised World Health Organization (WHO) classification, which distinguishes between low- and high-grade malignant GEP-NET, there is a lack of scintigraphic studies comparing uptake behavior on the basis of this categorization. This study aims to define predisposing factors of tracer uptake for both imaging principles implementing the updated tumor criteria of the current WHO classification.Fifty-seven consecutive patients with histologically confirmed metastatic GEP-NET evaluated with both 111In-pentetreotide and 123I/131I-MIBG scintigraphy were included in this study. Intensity of tracer uptake was graded according to the different metastatic regions. Patients were classified as overall positive when avid uptake in the clinically relevant tumor lesions was present. Correlation was tested between the proportion of positive patients and tumor origin, function, and malignancy.Overall, 52 patients (91.2%) were Oct positive and 28 patients (49.1%) were MIBG positive. The proportion of tracer-positive patients was significantly higher (P0.05) in low-grade malignant tumors for both tracers and in functioning as well as in gastroenteral NET for MIBG. Five patients were negative for both tracers. None of the Oct-negative patients proved to be MIBG positive.Oct affinity is observed with high frequency throughout the subgroups of metastatic GEP-NET, whereas corresponding MIBG uptake is overall less prevalent and more group dependent. Tumor differentiation significantly impacts both Oct and MIBG uptake, whereas functionality predisposes only for MIBG accumulation. Though clearly inferior to Oct-based radioimaging in most GEP-NET, MIBG achieves a remarkable rate of radioligand accumulation in functioning midgut enterochromaffin cell metastases (80% of patients positive). These results may have implications for patient management and potentially for selection and performance of targeted therapy.

Nicotinic acetylcholine receptors mediate the parasympathetic autonomic control of cardiac function. Aim of this study was the assessment of cardiac nicotinic acetylcholine receptor distribution with a novel (alpha4beta2) nicotinic acetylcholine receptor PET ligand (2-deoxy-2- [18F]fluoro-D-glucose-A85380) in humans. Five healthy volunteers without cardiac disease and six patients with either Parkinson's disease or multiple system atrophy without additional overt cardiac disease were evaluated with 2-deoxy-2-[18F]fluoro-D-glucose-A85380 PET-imaging to assess the cardiac parasympathetic innervation and the putative impact of both disorders. 2-deoxy-2- [18F]fluoro-D-glucose-A85380 whole body PET-scans were performed on a Siemens PET/CT biograph(TM) 75.4 min +/- 6.7 after i.v. injection of 371.2 +/- 58.1 MBq. Average count rate density of left ventricle ROI's and a standard ROI in the right lung were measured within three consecutive slices of 10.0 mm thickness. Heart-to-lung ratios were calculated in each volunteer and patient. Tracer uptake in the left ventricle could be measured in all of the five volunteers and the six patients. Heart-to-lung ratios in the volunteer group were not different from patients suffering from Parkinson's disease or MSA (3.2 +/- 0.5 vs 3.2 +/- 0.8 and 2.96+/-0.7, mean +/- SD), respectively. Human cardiac nicotinic acetylcholine receptors can be visualized and measured by 2-deoxy-2- [18F]fluoro-D-glucose-A85380 PET scans both in cardiac-healthy subjects and patients suffering from Parkinson's disease or multiple system atrophy. The heart- as well as the lung-tracer uptake was almost constant throughout all subjects leading to a good target-to-background ratio. These first results suggest no impact of either PD or MSA on cardiac nicotinic acetylcholine receptors.

Dear Sir, We read with great interest the recently published article by Campana et al. on outcome of peptide receptor radionuclide therapy (PRRT) and potential predictive factors [1]. This study included 69 patients regardless of whether Luor Y-based PRRT was applied. The authors concluded that stage of the disease (stage IV vs III), proliferation rate (G2 vs G1) and presence of previous transarterial chemoembolization (TACE) are significant factors for progression-free survival. Regarding the significance of the “tumour proliferation rate”, the authors stated in their discussion: “In general, it is well known that Ki-67 is a major prognostic factor for NETs. However, our data confirmed the role of tumour differentiation and Ki-67 as crucial therapeutic prognostic factors for response to PRRT in NETs as well.”Our group has previously evaluated this issue and the results have been published in the paper entitled “Impact of the Ki-67 proliferation index on response to peptide receptor radionuclide therapy” in the European Journal of Nuclear Medicine and Molecular Imaging in 2011 [2]. Unfortunately, this paper has not been cited by Campana et al. and is conspicuously missing in their discussion dealing with this topic. In our study, we specifically analysed the issue and were able to show that there was in fact no loss of response efficacy associated with higher proliferation indices in the G1–2 range, in particular not in NET with Ki-67 of 15–20 or 20 %. Our analysis was—in contrast to Campana et al. (n =63 patients with known Ki-67 index, either treated with Luor Y-based PRRT)—based on data of a uniformly treated cohort (n =81 patients receiving Lu-octreotate, all with characterized pretreatment proliferation rate). It is important to bring this paper to the reader’s attention as it provides a strong rationale not to preclude patients from PRRT because of proliferation indices in the high intermediate range (15–20 %). Another general comment on the study of Campana et al. is regarding analysis of predictive factors. It is reasonable to be more cautious in terms of validity of the multivariate analysis when applying such a large number of variables, where the number of patients is about 5 times the number of examined factors. The heterogeneity of the cohort not only of PRRT radiopharmaceuticals used (Y, Lu) but also stage of disease [n =15 patients (21.7 %) with stage III, i.e. with no distant metastases!] further weakens the analysis and might explain the discrepancy of results with previous reports on larger and more homogeneous cohorts regarding potential predictive factors [3, 4]. Thus, the discussion should be handled with particular care and conclusions should accordingly be attenuated. In summary, we like to point out that—as long as within the G1–2 range—increased Ki-67 indices should not serve as an argument against PRRTand call attention to the fact that this is supported by solid data, which may be referenced for any future multidisciplinary debates on this important issue.

Background: The human 5-HT 2 C receptor gene has been localized on the X chromosome and is expressed in two genetic variants. Whereas previous investigations have suggested that the 5-HT 2 C receptor gene polymorphism is critically involved in the pathogenesis of affective and eating disorders, as yet the functional consequences being associated with the rare serine variant of the 5-HT 2 C receptor in humans are unclear. Methods: We explored by HMPAO-SPECT if a challenge with the serotonin agonist mCPP, that interacts mainly with the 5-HT 2 C receptor, provokes different patterns of regional cerebral bloodflow (rCBF) as a function of the genetic variant of the receptor. Thus we studied its action in 16 healthy male volunteers carrying the common 5-HT 2 C -cys-23 receptor gene and 16 healthy male volunteers carrying the less frequent 5-HT 2 C -ser-23 receptor gene. Results: We found significant differences in rCBF between the two genotypes after mCPP infusion compared to placebo: In the cysteine group rCBF was increased in the left medial prefrontal cortex and decreased in the left anterior cingulate and right medio-temporal cortex, whereas the serine group showed an increase of rCBF in the left medio- and superior-temporal cortex and in cerebellum and a reduced rCBF in the right medial prefrontal cortex. In addition, there was a significant disordinal interaction of the genotype factors and challenge with an increase of rCBF in the serine group and a decrease in the cysteine group in the left motor cortex and calcarine cortex. Additionally, a decrease of rCBF in the serine-group and a simultaneous increase in the cysteine group was found in the right anterior and the left posterior cingulate cortex. Conclusion: These findings suggest that differences in the 5-HT 2 C receptor gene polymorphism has functional consequences due to a different responsiveness of the expressed 5-HT 2 C receptor variants.

Most patients with hepatocellular carcinoma are not eligible for surgery at the time of primary diagnosis. Portal vein thrombosis is frequent and represents a contraindication for transarterial chemoembolisation. Transarterial therapy with iodine-131-Lipiodol is superior to systemic therapy in tumours up to diameters of 5 cm and may be performed even in cases with portal vein thrombosis. Compared to other intraarterial therapy procedures, iodine-131-Lipiodol shows the same efficacy but less side effects.

Fluorine-18 fluoroacetate [1] appears to be an interesting alternative to 11C-acetate [2, 3] for imaging prostate cancer with PET. We acquired the first 18F-fluoroacetate PET images in a patient with prostate cancer, rising PSA (101 ng/ml) and progressive bone metastases. Scanning started 70 min after i.v. injection of 280 MBq 18F-fluoroacetate using a combined PET/CT system (Siemens Biograph). The images demonstrate moderate to intense uptake in several (thick arrows) but not all (thin arrows) metastatic bone lesions, with SUVmean of 2.82–4.10 and SUVmax of 3.36–5.11. This compared favourably to accumulation in the liver, with SUVmean of 2.35–2.71 and SUVmax of 3.0–3.58. The mode of excretion was predominantly via the bowel (arrowheads), with low activity in the urine. Compared with 11C-acetate PET, 18F-fluoroacetate offers the possibility of delayed imaging with the potential to further increase the tumour-to-background ratios. Upper row: CT image slices; middle row: combined 18F-fluoroacetate PET/CT; lower row: 18F-fluoroacetate PET References

Purpose: We investigated the effect of repeated bone-targeted therapy with rhenium-188 hydroxyethylidenediphosphonate (HEDP) in patients with progressive, hormone-resistant prostate carcinoma and bone pain. The aim of this study was to determine the pain palliation and the antitumor effect of rhenium-188 HEDP treatments. Patients and Methods: Sixty-four patients were randomly assigned to one of two groups for radionuclide therapy with rhenium-188 HEDP; patients of group A received a single injection, patients of group B received two injections (interval, 8 weeks). After therapy, patients were followed-up by assessment of pain palliation and clinical outcome until death. Results: In both groups, toxicity was low, with moderate thrombopenia and leukopenia (maximum common toxicity criteria grade of 2). The effectiveness of rhenium-188 HEDP for pain palliation was better in the repeated treatment group (group B), with a response rate and time of response of 92% and 5.66 months, respectively (P = .006 and P = .001). In group B, 11 (39%) of 28 patients had a prostate-specific antigen decrease of more than 50% for at least 8 weeks, compared with two (7%) of 30 patients in the single-injection group (group A). The median times to progression of group A and group B were 2.3 months (range, 0 to 12.2 months) and 7.0 months (range, 0 to 24.1 months), respectively (P = .0013), and the median overall survival times were 7.0 months (range, 1.3 to 36.7 months) and 12.7 months (range, 4.1 to 32.2 months), respectively (P = .043). Conclusion: Compared with single-injection therapy, repeated bone-targeted therapy with rhenium-188 HEDP administered to patients with advanced progressive hormone-refractory prostate carcinoma enhanced pain palliation and improved progression-free and overall survival. Larger studies are justified to further evaluate the use of rhenium-188 HEDP.

One assumption in emission tomograpy is the stability of activity distribution during acquisition. Thus, to detect movement of the patient, acquisition was splitted into two time segments. By calculating and comparing the centers of mass of the projections, evaluation of movement may be performed by means of two movement indicators: integral and total movement index. Depending on the movement of a phantom, iBI had values from 2.6 to 6 and the tBI values from 100 to 300. For Patients we obtained values of the iBI from 2.7 to 16 and of the tBI from 100 to 5000.

A 76-year-old man with colorectal cancer and hepatic metastases was referred to us for radioembolization of the liver. Angiography with 99mTc-MAA SPECT/CT was performed 8 weeks after the discontinuation of bevacizumab. 99mTc-MAA SPECT/CT showed a diffused intrahepatic tracer distribution with no focally accentuated accumulation in the tumorous region. The test was repeated 6 weeks later and Tc-MAA SPECT/CT showed this time a tumor accentuated tracer accumulation in the liver. Subsequently, the patient was treated with resin microspheres. Tc-MAA SPECT/CT allows a better evaluation of intrahepatic tracer accumulation of Tc-MAA and facilitates the determination of the most appropriate treatment time.

Galectin-3, a member of the galectin family of beta-galactoside-specific lectins has been found to be expressed by subsets of dorsal root ganglion (DRG) neurons during development and in adulthood. Here we show that (i) after 3-7 days in vitro, DRG neurons derived from neonatal mice express galectin-3 intra- and extracellularly and (ii) lectin expression requires the presence of nerve growth factor (NGF). After 3 days in vitro, a higher number of DRG neurons expressed galectin-3 in the presence of NGF (65 +/- 7%) than in the presence of brain-derived neurotrophic factor (BDNF, 30 +/- 3%) or neurotrophin-3 (NT-3, 34 +/- 3%). After 7 days in vitro, these numbers dropped to 51 +/- 3% (for NGF), 0% (for BDNF) and 8 +/- 4% (for NT-3), respectively. Our findings provide first evidence for the contribution of a neurotrophin to the neuronal expression of galectins and suggest an NGF/TrkA-mediated expression of galectin-3 by early postnatal DRG neurons.

We present a patient with thyroid cancer and hypopituitarism who required recombinant human thyrotropin (rhTSH) for I-131 Scanning with respect to subsequent therapy. The thyroid cancer had been unknown until central neurological symptoms developed, leading to the diagnosis of a huge metastasis to the sella that was the only manifestation of metastatic spread. The failure to generate endogenous thyrotropin (TSH) was overcome by the use of rhTSH for performing a I-131 test. Unfortunately, the I-131 uptake was not sufficient for therapy. This subject is the first reported case who required the application of rhTSH due to a single thyroid cancer metastasis in the sella region with secondary failure to generate endogenous TSH.

The aim of this multicentre study was to evaluate the clinical significance of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in differentiated thyroid carcinoma and to compare the results with both iodine-131 whole-body scintigraphy (WBS) and technetium-99m 2-methoxyisobutylisonitrile (MIBI) or thallium-201 chloride (Tl) scintigraphy. Whole-body PET imaging using FDG was performed in 222 patients: 134 with papillary tumours, 80 with follicular tumours and 8 with mixed-cell type tumours. Finally, for each case an overall clinical evaluation was done including histology, cytology, thyroglobulin level, ultrasonography, computed tomography and subsequent clinical course, to allow a comparison with functional imaging results. Sensitivity of FDG-PET was 75% and 85% for the whole patient group (n = 222) and the group with negative radioiodine scan (n = 166), respectively. Specificity was 90% in the whole patient group. Sensitivity and specificity of WBS were 50% and 99%, respectively. When the results of FDG-PET and WBS were considered in combination, tumour tissue was missed in only 7%. Sensitivity and specificity of MIBI/Tl were 53% and 92%, respectively (n = 117). We conclude that FDG-PET is a sensitive method in the follow-up of thyroid cancer which should be considered in all patients suffering from differentiated thyroid cancer with suspected recurrence and/or metastases, and particularly in those with elevated thyroglobulin values and negative WBS.

For patients with metastatic prostate cancer, first results have shown that rhenium-186 (Re-186) hydroxyethylidene diphosphonate (HEDP) is efficient in pain palliation of disseminated bone metastases. The aim of this study was to determine whether significant pain reduction can also be achieved in breast cancer patients with Re-186 HEDP.Thirty patients with breast cancer who had multifocal painful bone metastases received a total of 38 intravenous Re-186 HEDP injections. Pain relief was assessed through daily documentation of the visual analog scale and analgesic consumption. A significant response to treatment was determined if the visual analog scale or analgesic consumption decreased significantly for at least 2 weeks. Blood counts were controlled at baseline and at weeks 4 and 8.A response to pain therapy was observed in 60% (18 of 30) of the patients. A reversible thrombocytopenia and leukopenia of grade 2 (according to World Health Organization criteria) was found in 4 and 2 patients, respectively.Patients with disseminated osseous metastases resulting from breast cancer can benefit from therapy with Re-186 HEDP.

Magnetic resonance imaging (MRI) was performed on an infant with typical complex partial seizures. Visual analysis revealed MRI signs of left hippocampal sclerosis (HS) at an age of 9 months. Morphometric data including volumetry and relaxometry confirming the diagnosis are shown. This is the first report of an infant younger than 2 years with typical MRI findings including morphometric data on HS.J. Magn. Reson. Imaging 1999;10:93–96. © 1999 Wiley-Liss, Inc.

A 67-year-old woman with a history of malignant melanoma in the right lower leg for 7 years without any known metastases was hospitalized for evaluation of severe left upper quadrant abdominal pain. Computed tomography of the abdomen revealed a suspected splenic mass. F-18 FDG PET/CT imagin

The aim of the trial was to determine the diagnostic accuracy of scintimmammography with technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) in the detection of primary breast cancer and to verify its clinical usefulness. A total of 246 patients with a suspicious breast mass or positive mammogram were included in this prospective European multicentre trial. At 5 min and 60 min (optional) p.i. two lateral prone images were acquired for 10 min each; 30 min p.i. one anterior image was acquired for 10 min. There were 253 lesions (195 palpable and 58 non-palpable), in respect of which histology revealed 165 cancers and 88 benign lesions. Institutional and blinded read results were correlated to core laboratory histopathology results obtained during excisional biopsy. Diagnostic accuracy for the detection of breast cancer was calculated per lesion. The overall sensitivity and specificity of blinded read scintimammography were 71% and 69%, respectively. For palpable lesions, the sensitivity of blinded read and institutional read scintimammography was 83% and 91%, respectively. Sensitivity was not dependent on the density of the breast tissue. Invasive ductal and invasive lobular cancers showed similar sensitivity. The sensitivity and specificity of mammography were 91% and 42%, respectively, and did not depend on the tumour size. In 60% of false-negative mammograms, 99mTc-MIBI was able to diagnose malignancy (true-positive). High-quality imaging with 99mTc-MIBI has a high diagnostic accuracy for the detection of primary breast cancer. Used as a complementary method, scintimammography with 99mTc-MIBI can help to diagnose breast cancer at an earlier stage in patients with dense breasts.