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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.

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

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.