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Medullary thyroid carcinoma (MTC) is one of the most challenging cancers. Epidemiological studies have shown that during the past 30 years neither a change in stage at diagnosis nor a significant improvement in survival has been achieved. Therefore, new diagnostic and therapeutic strategies are needed for early detection of metastases or disease recurrence and tumor growth control.

Introduction The aim of this study was to assess the utility of [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 scintigraphy in the management of patients with hypoglycemia, particularly in the detection of occult insulinoma. Materials and Methods Forty patients with hypoglycemia and increased/confusing results of serum insulin and C-peptide concentration and negative/inconclusive results of other imaging examinations were enrolled in the study. In all patients GLP-1 receptor imaging was performed to localise potential pancreatic lesions. Results Positive results of GLP-1 scintigraphy were observed in 28 patients. In 18 patients postsurgical histopathological examination confirmed diagnosis of insulinoma. Two patients had contraindications to the surgery, one patient did not want to be operated. One patient, who presented with postprandial hypoglycemia, with positive result of GLP-1 imaging was not qualified for surgery and is in the observational group. Eight patients were lost for follow up, among them 6 patients with positive GLP-1 scintigraphy result. One patient with negative scintigraphy was diagnosed with malignant insulinoma. In two patients with negative scintigraphy Munchausen syndrome was diagnosed (patients were taking insulin). Other seven patients with negative results of 99mTcGLP-1 scintigraphy and postprandial hypoglycemia with C-peptide and insulin levels within the limits of normal ranges are in the observational group. We would like to mention that 99mTc-GLP1-SPECT/CT was also performed in 3 pts with nesidioblastosis (revealing diffuse tracer uptake in two and a focal lesion in one case) and in two patients with malignant insulinoma (with the a focal uptake in the localization of a removed pancreatic headin one case and negative GLP-1 1 scintigraphy in the other patient). Conclusions 99mTc-GLP1-SPECT/CT could be helpful examination in the management of patients with hypoglycemia enabling proper localization of the pancreatic lesion and effective surgical treatment. This imaging technique may eliminate the need to perform invasive procedures in case of occult insulinoma.

Material and Methods Within the group of 47 patients treated with peptide receptor radionuclide therapy (PRRT), four patients were chosen: three with inoperable tumors without liver metastases and one with two lesions in the pancreas and metastases. Results In all patients, after PRRT, the changes in the sum of the longest diameters of tumors were between −1% and −21%, resulting in stable disease reported [strict Response Evaluation Criteria in Solid Tumors (RECIST)]. But the measurements of tumor volume and attenuation in computed tomography and the tumor to nontumor ratio in somatostatin receptor scintigraphy resulted in different response assessments. Conclusions The RECIST standard may be not sufficient to properly assess the therapy response in patients with neuroendocrine tumors.

Purpose Neuroendocrine tumours (NET) are a heterogeneous group of neoplasms of diffuse neuroendocrine cells. Surgery is the main aim in the treatment of NETs, which becomes impossible in the case of large tumours or infiltration into other tissues and/or important blood vessels. Neoadjuvant therapy might be helpful in decreasing NET size also, leading us to the point where a tumour, previously considered inoperable, becomes operable. The aim of the study was to assess the usage of peptide receptor radionuclide therapy (PRRT) as a neoadjuvant treatment, enabling surgical intervention in primary inoperable NET. Methods Among 47 patients treated with PRRT, 6 patients were chosen with large, inoperable tumours, for whom enabling of complete surgical excision of the lesions might offer the prospect for a cure. Response to the therapy was assessed according to Response Evaluation Criteria In Solid Tumors (RECIST). Results The mean tumour size decreased from 6.9 (min. 3.1 cm, max. 9.6 cm) before therapy to 5.4 cm (min. 3.1 cm, max. 9.5 cm) after the treatment. According to RECIST, stabilization of the disease was observed in four and partial responses in two patients. In two patients, reduction of the tumour size enabled surgical intervention. Conclusion (1) PRRT might be considered a neoadjuvant therapy in primary inoperable NETs. (2) According to RECIST, stabilization of the disease was observed in the majority of patients. (3) We suggest that not only tumour diameter changes, but also tumour volume and contrast enhancement changes in computed tomography should be taken into consideration in assessment of the response to the therapy. (4) Somatostatin receptor scintigraphy is an important tool for qualification of the radioisotope therapy and also for the assessment of the response to PRRT.

This study aimed to investigate the level of the eye lens (EL) doses in nuclear medicine in the light of the new International Commission on Radiological Protection limit. In 7 Belgian and 1 Polish hospitals, 45 staff members were monitored for EL (Hp(3)) and whole-body (WB) (Hp(10)) doses using dedicated dosemeters. Weekly measurements were carried out and used to estimate annual doses. Mostly diagnostic procedures involving radionuclides such as (99m)Tc and (18)F were monitored; measurements were also performed for therapeutic procedures. The cumulative doses showed important variation across the participants. The weekly EL and WB doses ranged from 0.02 to 0.27 and 0.03 to 0.17 mSv, respectively; the annual EL and WB doses ranged from 0.6 to 9.3 and 0.9 to 8.0 mSv, respectively. Some correlation was found between the EL and the WB doses. No significant correlation with the manipulated activities was found.

Mammography provides early micro-calcification recognition, that is important for further breast cancer (BC) diagnosis. Imaging choice for BC detection is X-ray mammography (MG) with the use of high-resolution digital modality combined with iodinated contrast agents. However, a conventional MG has some sensitivity limitations, especially in patients with densely treated breasts. Moreover, MG contributes radiation risk for BC that is correlated with an exposure to ionizing radiation. Patients, for whom MG study does not give a clear interpretation are often further diagnosed by contrast-enhanced breast MRI, the most sensitive BC detection technique. Alternatively, it is limited by higher costs, lower availability and increased false positives. Dual-energy contrast-enhanced spectral mammography (CESM) is a new method applied in BC that enables accurate detection of malignant breast lesions similar to breast MRI. The aim of this study was to compare the usefulness of CESM versus MG in BC detection. Additionally, doses given to the BC patients during imaging were compared. In this study, 250 consecutive women (144 MG vs. 105 CESM), that were screened using mammography between 2011 and 2014 were retrospectively enrolled in the study. The comparison of entrance surface air kerma and mean glandular dose values for both options were recorded, respectively and analyzed using different statistical and retrospective approach. Results of presented study showed that CESM might be a new diagnostic tool allowing an accurate detection of BC lesions, giving results similar to those received from magnetic resonance imaging. A good agreement found between sensitivity of the method and tumour diameters measurements based on CESM, supports this tool as a potential replacement for breast MRI in the preoperative evaluation of BC patients. However, a radiation burden for patients might be significantly higher than that for a standard full-field digital mammography procedure. In summary, each method has its own benefits with respect to specific applications that are further discussed in the study. Citation Format: Kamila Rawojc, Kamil Kisielewicz, Anna Dziecichowicz, Monika Tomaszuk, Anna Cepiga, Jankowska Anna, Cieśla Izabela, Najberg Dominika, Luczynska Elzbieta, Bartosz Kieltyka. Exposure burden for patients during an experimental study using a dual-energy contrast-enhanced spectral mammography [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3742. doi:10.1158/1538-7445.AM2017-3742

One of the major procedures for testing the geometrical accuracy of devices used in radiotherapy treatments is the test of the geometrical position of the radiation isocenter. The importance of the test reflects the fact that geometrical position of the radiation isocenter generally affects the tumor targeting. At present the geometric accuracy is assessed with the Winston-Lutz test which checks the position of an image of a ball marker with the respect to the center of the radiation field as projected on a detector plane. Obviously, determination of coordinates of a single marker is not sufficient to fully account for a complicated geometry of a therapeutic device. The purpose of the study was to design a new image analysis tool to better determine the isocenter. The proposed automated procedure for determining isocenter position uses projection data acquired for a special cube phantom. The projection images of a phantom are acquired for various angles of rotation of the gantry. A procedure is proposed to extract some geometric characteristics of a therapeutic device from the projection images.

BACKGROUND: Somatostatin receptor scintigraphy (SRS) is a useful tool in the assessment of GEP-NET (gastroenteropancreatic neuroendocrine tumor) patients. The choice of appropriate settings of image reconstruction parameters is crucial in interpretation of these images. The aim of the study was to investigate how the GEP NET lesion signal to noise ratio (TCS/TCB) depends on different reconstruction settings for Flash 3D software (Siemens). METHODS: SRS results of 76 randomly selected patients with confirmed GEP-NET were analyzed. For SPECT studies the data were acquired using standard clinical settings 3–4 h after the injection of 740 MBq 99mTc-[EDDA/HYNIC] octreotate. To obtain final images the OSEM 3D Flash reconstruction with different settings and FBP reconstruction were used. First, the TCS/TCB ratio in voxels was analyzed for different combinations of the number of subsets and the number of iterations of the OSEM 3D Flash reconstruction. Secondly, the same ratio was analyzed for different parameters of the Gaussian filter (with FWHM = 2–4 times greater from the pixel size). Also the influence of scatter correction on the TCS/TCB ratio was investigated. RESULTS: With increasing number of subsets and iterations, the increase of TCS/TCB ratio was observed. With increasing settings of Gauss [FWHM coefficient] filter, the decrease of TCS/TCB ratio was reported. The use of scatter correction slightly decreases the values of this ratio. CONCLUSIONS: OSEM algorithm provides a meaningfully better reconstruction of the SRS SPECT study as compared to the FBP technique. A high number of subsets improves image quality (images are smoother). Increasing number of iterations gives a better contrast and the shapes of lesions and organs are sharper. The choice of reconstruction parameters is a compromise between image qualitative appearance and its quantitative accuracy and should not be modified when comparing multiple studies of the same patient.

Background and purpose Hydrogen magnetic resonance spectroscopy ( 1 HMRS) is nowadays one of the basic tools for noninvasive brain metabolism assessment. The study focuses on the important problem of the influence of hormone fluctuation during the menstrual cycle on brain metabolism, assessed by 1 HMRS for clinical diagnostics. Material and methods In 11 healthy regularly menstruating women, 1 HMRS was performed at the start (phase I), in the middle (phase II) and at the end (phase III) of the menstrual cycle. The relative concentration ratios of 12 brain metabolites in every woman in all cycle phases were examined, in 6 different volumes of interest (VOIs). Finally, statistically significant differences in relative metabolite ratios between the phases examined in given locations were sought. Results Statistically significant relations between menstrual cycle phases and relative ratios of 4 metabolites – Lac/Cr, NAA/Cr, Glx1/Cr and Glx2/Cr – in different brain locations were found. In all locations, mean NAA/Cr ratios were greater in phase I compared to the other phases. A similar relationship was found for Glx1/Cr ratio in one location (left occipital lobe). For Lac/Cr and Glx2/Cr ratios, a higher mean ratio value was obtained in phase II compared to phases I and III in the right occipital lobe and left basal ganglia, respectively. Conclusions Menstrual cycle phase should be considered in planning a date and interpretation of 1 HMRS examination, performed for the verification of a disease manifesting as brain metabolite disturbances in the 1 HMRS spectrum.

Purpose The objective of this article is to present a new method for the diagnosis of insulinoma with the use of [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4. Methods Studies were performed in 11 patients with negative results of all available non-isotopic diagnostic methods (8 with symptoms of insulinoma, 2 with malignant insulinoma and 1 with nesidioblastosis). In all patients glucagon-like peptide-1 (GLP-1) receptor imaging (whole-body and single photon emission computed tomography/CT examinations) after the injection of 740 MBq of the tracer was performed. Results Both sensitivity and specificity of GLP-1 receptor imaging were assessed to be 100 % in patients with benign insulinoma. In all eight cases with suspicion of insulinoma a focal uptake in the pancreas was found. In six patients surgical excision of the tumour was performed (type G1 tumours were confirmed histopathologically). In one patient surgical treatment is planned. One patient was disqualified from surgery. In one case with malignant insulinoma pathological accumulation of the tracer was found only in the region of local recurrence. The GLP-1 study was negative in the other malignant insulinoma patient. In one case with suspicion of nesidioblastosis, a focal accumulation of the tracer was observed and histopathology revealed coexistence of insulinoma and nesidioblastosis. Conclusion [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 seems to be a promising diagnostic tool in the localization of small insulinoma tumours, but requires verification in a larger series of patients.

This chapter describes the possibility of using peptide receptor radionuclide therapy (PRRT) as neoadjuvant treatment. PRRT is acknowledged to be a palliative treatment. Recently it has been reported that tumor size decrease followed by surgical intervention might be achieved in patients with neuroendocrine tumors (NETs) treated with somatostatin analogs labeled with beta emitters. Such outcome of therapy has been described in a relatively small group of patients. In those patients, the treatment enabled total or partial excision of the tumor, also with liver metastases. Reduction of tumor dimensions or total excision of the tumor corresponded with prolongation of overall survival. The discussed papers on this subject differ in details of treatment (utilization of various isotopes, total activity of the isotope, or combination with radiosensitizing chemotherapy). The chapter presents a brief review of recently published manuscripts.

Purpose PRRT is a known tool in the management of patients with disseminated and inoperable NETs. The aim of study was to assess the effectiveness of the repeated cycles of PRRT in patients with disseminated and inoperable NETs. Material and methods Eighty nine patients were included in the PRRT. Among them 16 patients (18%) were qualified for a repeated PRRT cycle due to progression of the disease. In one of the patients qualified for the repeated cycle, PRRT was used as neoadjuvant therapy. The results and side-effects of the repeated cycles of PRRT were analyzed. Results Disease stabilization was observed in 10 patients 6 months after the repeated PRRT cycle and in 5 patients after 12 and 18 months. Ten of the patients who had received repeated PRRT cycles died. In the case of neoadjuvant therapy, further reduction of the tumor size was observed, enabling qualification for surgery. Clinically significant reduction in the mean values of morphological parameters was not observed. Only after 12 and 18 months the mean values of creatinine levels were higher than the normal range (only in 2 patients). Conclusions The repeated cycles of PRRT did not cause a clinically significant increase of the toxicity of PRRT. The changes in kidney and blood morphology parameters were transient. The repeated cycles of PRRT enabled stabilization of the disease.

BACKGROUND: The aim of the study was to assess the effectiveness of peptide receptor radionuclide therapy (PRRT) in patients with non-functioning neuroendocrine pancreatic tumours (NFPNTs) and to compare survival rates in patients with NFPNTs and in patients with other neuroendocrine tumours (NETs) treated using radiolabelled somatostatin analogue in our Department. We would like to analyze factors potentially determining the effectiveness of the therapy and also to assess the myelo- and nephrotoxicity. MATERIAL AND METHODS: Fourteen patients with disseminated disease and/or inoperable NFPNT were qualified to PRRT based on positive SRS (somatostatin receptor scintigraphy). There were 5 men and 9 women, with Karnofsky’s index > 70%. RESULTS: In the whole group of patients, partial response was observed in 21.4%, stabilization of the disease in 42.9%, and progression of the disease in 35.7% of patients. Mean observation time was 19 ± 13 months, mean time to progression was 12 ± 9 months, and mean time to death was 16 ± 9 months. Six patients died — four of them due to progression of the disease, two due to myocardial infarction. After PRRT we did not observe clinically significant haemotoxicity and/or nephrotoxicity. CONCLUSIONS: 1. Peptide receptor radionuclide therapy may be a safe and effective treatment option in patients with NFPNTs, leading to stabilization or regression of the disease in the majority of patients. 2. There is no statistically significant difference in survival rate between patients with NFPNTs and NETs of other localization treated with PRRT. Nuclear Med Rev 2011; 14, 2: 73–78

Dear Sir, In a recent article, Pepe et al. presented a review of the development of compounds for the study of somatostatin receptors and their application in diagnostic imaging [1]. In this very interesting paper the proven effectiveness of labelled somatostatin analogues in the management of patients with various somatostatin receptor-positive diseases is presented (among others its role as a historical turn in the clinical practice and diagnosis of gastroenteropancreatic neuroendocrine tumours, GEP NET). Although we appreciate very much this issue of the European Journal of Nuclear Medicine and Molecular Imaging devoted to the most important aspects of the usefulness of somatostatin analogues, we would like to comment on some statements from the review by Pepe et al. In this paper we read: “Given the importance and success of 99mTc as a routine isotope in nuclear medicine imaging, it came as a logical consequence that 99mTc-labelled somatostatin analogues have been developed, namely the 99mTc-N-α-(6-hydrazinonicotinoyl)-octreotide (99mTc-EDDA/HYNIC OCT). At that time propagation of the tracer was hampered by proprietary rights on the peptide. For this reason it has remained a tracer for in-house use.” To our knowledge 99mTc-EDDA/HYNIC-TOC is the radiopharmaceutical most frequently used for the scintigraphic visualization of sst-positive tumours in Poland. This tracer was registered in Poland in 2004. It is also successfully used in many other European countries according to their national regulations, so calling the availability of this tracer “in-house use” only seems to be disappointing. 99mTc-Labelled radiopharmaceuticals, compared with for example 111In-labelled compounds, may improve the quality of images and radiation safety for patients and the staff as a natural consequence of this isotope’s physical properties. As it was stated in another review from this issue by Fani and Maecke 99mTc is the “workhorse” in diagnostic nuclear medicine not without a reason [2]. Also one could read there about the labelling procedure of somatostatin analogues with 99mTc, which may be evaluated as relatively cheap and easily employed in any nuclear medicine hot lab, as well as with high labelling yield and radiochemical purity of the compound assured by the manufacturer and confirmed in our experience. It was shown that 99mTc-EDDA/HYNIC-TOC reveals high in vitro and in vivo stability, fast background clearance, relatively low accumulation in non-target tissues and rapid detection of somatostatin receptor-positive tumours. Decristoforo et al. and Gabriel et al. studied the imaging abilities of 99mTc-EDDA/HYNIC-TOC compared to Octreoscan [3, 4]. The authors stated that 99mTc-EDDA/HYNIC-TOC was characterized by higher tumour to normal tissue ratios than Octreoscan. A higher target to non-target ratio was also reported by Gabriel et al. for somatostatin receptor scintigraphy (SRS) with the use of 99mTc-N4-[Tyr3]octreotate (99mTc-Demotate) in comparison also to Octreoscan [5]. 99mTc-EDDA/HYNIC-TOC revealed a higher sensitivity for NET detection than Octreoscan (65.9 vs 51.2 %) [4]. More focal lesions were also detected, especially small liver and lymph nodes metastases (125 vs 90 lesions). This fact was probably related to four times higher 99mTc injected activity in comparison to 111In as well as a higher receptor affinity to 99mTc-labelled somatostatin analogues. In the paper by Chrapko et al. [6] about daily clinical practice with the use of 99mTc-EDDA/HYNIC-TOC SRS, the authors concluded that 99mTc-EDDA/HYNIC-TOC SRS is useful in staging as well as in restaging after primary tumour surgery of sst-positive tumours including tumours of unknown primary origin. Following 99mTc-EDDA/HYNIC-TOC, the Tyr3-octreotate (TATE) somatostatin analogue was introduced. It is also octreopeptide and differs from the Tyr3-octreotide (TOC) in that the terminal threonine replaces threoninol. The terminal threonine results in a higher receptor binding and better internalization, with the consequence that tumour uptake of the tracer is intense. In vitro studies revealed that TATE, whether chelated with DTPA or DOTA, shows 14- to 17-fold higher affinity to sst2 than octreotide and 8- to 10-fold higher affinity than TOC. In studies performed by our group the favourable pharmacokinetic parameters of this tracer were shown [7]. Taking into account Polish experiences with the use of 99mTc-EDDA/HYNIC-TATE, the focal lesions were better visualized by this tracer than by Octreoscan. It seems to be connected with higher affinity of [Tyr3]octreotate to sst2 and better special resolution due to 99mTc physical properties. These results are consistent with the outcomes of preclinical studies which indicated that [Tyr3]octreotate radiotracers were characterized by the stated good sst2 affinity and high degree of internalization of this somatostatin analogue in tumour cells. Application of 99mTc-EDDA/HYNIC-TATE SRS followed by radio-guided surgery (RGS) may significantly improve the rate of detection and efficacy of treatment of NETs of the gastrointestinal tract (GEP NET), especially in the presence of occult endocrine tumours. The imaging properties of 99mTc-EDDA/HYNIC-TATE and possible 1-day imaging protocol creates potential for more common application of this tracer in oncology [8]. On the basis of available publications and Polish experiences since 2004, it can be concluded that 99mTc-labelled somatostatin analogues essentially improved diagnostic efficacy and contribute to optimization of the neuroendocrine patients therapeutic procedure. The tracers are used for localization of sst-positive tumours and their metastases and above all as part of peptide receptor radionuclide therapy (PRRT) (qualification to 90Y, 177Lu or 90Y/177Lu radionuclide therapy and further control of therapy effectiveness) and “cold” somatostatin analogue therapy. Although it is expected that in future positron emission tomography (PET) examinations with the use of somatostatin analogues labelled with 68Ga will replace any other forms of sst-receptor positive tumour examinations, until then SRS with the use of analogues labelled with 99mTc may be still considered a good alternative for the departments without PET scanners. From our point of view, 99mTc-labelled somatostatin analogues are important and effective members of the radiolabelled peptide family.

Overexpression of glucagonlike peptide-1 (GLP-1) receptors in human tumours is a potential target for future imaging and therapy. The GLP-1 receptor imaging using [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 could be useful in the localization of unknown insulinoma focus. The aim of this study was to present the first experience of our unit with the new radiopharmaceutical and its dose estimates. Imaging studies and dose assessment, according to the MIRD schema and MIRD Pamphlet No.11, were performed for 3 patients (2 with suspicion of insulinoma, 1 with suspected insulinoma recurrence). In the first case suspicion of insulinoma was not confirmed. In the second case localized accumulation of tracer in the pancreas was removed by surgery and the clinical symptoms of insulinoma receded. In the third case, pathological accumulation of tracer was localized and recurrence of insulinoma was confirmed in fusion with CT images. The biological half-time did not exceed 2.7.h. The effective half-time did not exceed 4.8 h. The total-body radiation dose did not exceed 0.0038 mGy/MBq and is comparable with the radiation dose to patient after somatostatin receptor scintigraphy. The highest radiation dose was calculated for kidneys (~ 0.070 mGy/MBq). [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 is a good candidate for clinical GLP-1 receptor imaging studies and appears safe for the patient from radiological safety point of view.