Comparison of receptor affinity of natSc-DOTA-TATE versus natGa-DOTA-TATE

BACKGROUND: 44Sc as a positron emitter can be an interesting alternative to 68Ga (T½ = 67.71 min) due to its longer half-life (T½ = 3.97 h). Moreover, the b– emitter 47Sc can be used for therapy when attached to the same biomolecule vectors. DOTA as a chelating agent has been proven suitable for the radiolabelling of peptides recognising tumour cell receptors in vivo with M3+ radiometals. DOTA-derivatized peptides have been successfully labelled with 90Y and 177Lu for therapy, and with 68Ga for PET imaging. However, published data on 44Sc-labelled DOTA-biomolecules as potential PET radiotracers are still very limited. The aim of this study was to compare the affinity of natGa- and natSc-labelled DOTA-TATE to somatostatin receptors subtype 2 expressed in rat pancreatic cancer cell line AR42J. MATERIAL AND METHODS: The cold complexes of DOTA-TATE with natGa and natSc were synthesized and identified by HPLC and MS analysis and evaluated in vitro for competitive binding to cancer cell line AR42J expressing somatostatin receptors subtype 2 (sstr2). RESULTS: The IC50 values calculated from the displacement curve of {125I-Tyr11}-SST-14 were: 0.20 ± 0.18, 0.70 ± 0.20, 0.64 ± 0.22 and 0.67 ± 0.12 for natGa-DOTA-TATE, natSc-DOTA-TATE, DOTA-TATE, and {Tyr11}-SST-14 complexes, respectively, with the affinity lowering in the decreasing order: natGa-DOTA-TATE > DOTA-TATE > Tyr11-SST-14 > natSc-DOTA-TATE. CONCLUSIONS: The binding affinity of natGa-DOTA-TATE appeared higher than that of natSc-DOTA-TATE. Further in vitro and in vivo studies are needed to verify the influence of the chelated metal on the affinity and uptake of the respective radiolabelled compounds. This information might be crucial when the in vivo applications of peptides labelled with 68Ga and 44Sc for PET, as well as the use of 47Sc for radiotherapy are considered. Nuclear Med Rev 2011; 14, 2: 85–8

Evaluation of radiological and clinical efficacy of ^{90}Y-DOTATATE} therapy in patients with progressive metastatic midgut neuroendocrine carcinomas

Background: To evaluate the radiological and clinical therapeutic effectiveness of ^{90}Y-octreotate [DOTATATE] inpatients with progressive somatostatin receptor-positive midgut neuroendocrine carcinomas (GEPNETs). Material/Methods: The study group: 34 patients, with histological proven extensive non-resectable and progressive midgut GEP-NETs. Radionuclide therapy (^{90}Y-DOTATATE) was given i.v. with a mean activity per administration 3,82 GBq. Initial clinical tumor responses were assessed 6-7 weeks after therapy completion and then once 3-monthly. The objective tumor response was classified according to the RECIST, initially between 4-6 months and then after each of the 6 months interval. Results: At 6 months after treatment completion, radiological tumor response was observed in 6 subjects with PR (19%), 25 presented SD (78%) and single had PD (3%). Overall clinical response to therapy at 6 months follow-up was observed in 23 patients (68%), SD in 5 patients (15%) and PD in 6 (18%). A year after therapy radiological tumour response was seen in 11 patients (44%), SD had 12 subjects (44%) and DP was noted in 2 patients. Two years after completed therapy PR was seen in 6 patients (33%), SD in additional 11 subjects (61%), single patient had PD. Clinical response to treatment in terms of PR and SD were noted in 22 patients (88%) after 1 year and in 14 patients (87%) after 2 years. Median PFS was 20 months, while the median OS was 23 months. In the 6 patients with clinical PD within initial 6 months the median PFS was 6 months and OS 11 months, while in those with SD or PR PFS was 22 months and OS 26 months (P<0.05). Conclusions: Therapy with ^{90}Y-DOTATATE} is effective in terms of clinical response, however the radiological response measured by the RECIST criteria underestimates benefits of this type of therapy in patients with progressive somatostatin receptor-positive midgut neuroendocrine carcinomas

99mTc-EDDA/HYNIC-octreotate - a new radiotracer for detection and staging of NET. A case of metastatic duodenal carcinoid

Somatostatin receptor scintigraphy (SRS) has become a routine imaging method for the diagnostics of neuroendocrine tumours (NET). 99mTc-EDDA/HYNIC-octreotate (Polatom, Poland) is a new radiotracer with high affinity for SSTR2 and similar physiological biodistribution to 111In-Octreoscan. We present a case of a 47-year-old man with disseminated duodenal carcinoid. The patient had been operated due to the tumour mass detected in pancreatic head area. Histopathology revealed carcinoid of the duodenal wall with local lymph node and liver metastases. The patient was qualified for chemotherapy stopped due to severe leucopenia. 99mTc EDDA/HYNIC-octreotate scintigraphy was performed for staging and to determine SSTR status of the tumour before planned 90Y-DOTATATE therapy. The multiple metastatic lesions were detected all over the body. The high quality images with high target/non target ratio were obtained. 99mTc-MDP scintigraphy confirmed multiple bone metastases. On the basis of SRS result the patient was qualified for 90Y-DOTA-TATE therapy. In conclusion, 99mTc EDDA/HYNIC-octreotate can be regarded as a promising tracer for staging and to determine SSTR status of NET

Lu-177-labeled zirconia particles for radiation synovectomy

The present article describes the preparation of beta emitter lutetium-177-lebeled zirconia colloid and its preliminary physico-chemical and biological evaluation of suitability for local radionuclide therapy. The new 177Lu-labeled therapeutic radiopharmaceutical candidate was based on the synthesis mode of a previously described zirconia nanoparticle system. Morphology and size of developed radiopharmaceutical compound were evaluated through scanning electron microscope and dynamic light scattering methods. The radiocolloid had a 1.7 micrometer mean diameter and showed suitable radiolabeling and colloid size in vitro stability at RT and during blood sera stability test. After the in vitro characterizations, the product was investigated in the course of the treatment of a spontaneously diseased dog veterinary patient’s hock joint completed with SPECT imaging follow-up measurements and a dual-isotope SPECT imaging tests with conventional 99mTc-MDP bone scintigraphy. In the treated dog any clinical side effects or signs of histopatological alterations of the joints could not be observed during the treatment. SPECT follow-up studies unequivocally showed appropriately high localization of the 177Lu-labeled colloid in hock joint and detectable but negligible radiocolloid leakages in the nearest lymph node, respectively

Guidance on current good radiopharmacy practice (cGRPP) for the small-scale preparation of radiopharmaceuticals

This guidance is meant as a guidance to Part B of the EANM “Guidelines on Good Radiopharmacy Practice (GRPP)” issued by the Radiopharmacy Committee of the EANM (see www.eanm.org), covering the small-scale “in house” preparation of radiopharmaceuticals which are not kit procedures. The aim is to provide more detailed and practice-oriented guidance to those who are involved in the small-scale preparation of, for example, PET, therapeutic or other radiopharmaceuticals which are not intended for commercial purposes or distribution

Efficacy and safety of 90Y-DOTATATE therapy in neuroendocrine tumours

Wstęp: Celem pracy była ocena skuteczności oraz toksyczności celowanej terapii receptorowej (PRRT) guzów neuroendokrynnych z wykorzystaniem analogu somatostatyny Tyr3-octreotate znakowanego 90Y (90Y-DOTATATE). Materiał i metody: Do badania włączono 46 pacjentów z rozsianym lub nieoperacyjnym guzem NET. 90Y-DOTATATE podawano w 3&#8211;5 kursach w odstępach 4&#8211;9-tygodniowych. Każdorazowo wyznaczano aktywność terapeutyczną, uwzględniając taką całkowitą powierzchnię ciała, by nie przekroczyć sumarycznej wartości 7,4 GBq/m2. Przed terapią i po niej wykonano oznaczenia parametrów morfotycznych, nerkowych oraz wątrobowych, a także stężenia chromograniny A. Wyniki: Spośród 46 leczonych pacjentów jeden chory zmarł przed zakończeniem pełnego cyklu terapeutycznego, a 16 po zakończeniu terapii, w tym jeden z powodu zawału serca. W 12. miesiącu obserwacji stwierdzono 47% stabilizacji, 31% częściowych odpowiedzi oraz 9% progresji wśród 45 pacjentów, którzy ukończyli leczenie. Pięciu chorych zmarło przed 12. miesiącem obserwacji. W jednym przypadku utracono możliwość uzyskania informacji o chorym po 12 miesiącach. Okres czasu bez progresji choroby wyniósł 37,4 miesiąca. W ciągu pierwszego roku od zakończenia terapii zaobserwowano jedynie przejściowe obniżenie wartości morfotycznych krwi oraz przejściowy wzrost stężenia kreatyniny i spadek wartości przesączania kłębuszkowego (GFR). Wnioski: Celowana terapia receptorowa z użyciem 90Y-DOTATATE może być skuteczną oraz stosunkowo bezpieczną metodą leczenia prowadzącą do częściowej odpowiedzi lub stabilizacji choroby u większości pacjentów. (Endokrynol Pol 2011; 62 (5): 392&#8211;400)Background: The aim of this study was to assess the efficacy and toxicity of peptide receptor radionuclide therapy (PRRT) with the use of the high affinity somatostatin receptor subtype 2 analogue, 90Y labelled Tyr3-octreotate, (90Y-DOTATATE) in neuroendocrine tumours (NETs). Material and methods: 46 patients with disseminated or non-operable NET were enrolled in this study. The 90Y-DOTATATE therapeutic activity was calculated per total body surface area up to a total of 7.4 GBq/m2 administered in three to five cycles, repeated every four to nine weeks. Before and after the therapy, blood tests for haematology, kidney and liver function, and chromogranin A were performed. Results: Out of 46 90Y-DOTATATE treated patients, one died before completing the therapy and 16 died after completing the therapy, among them one due to myocardial infarction. After 12 month follow-up, stabilisation of disease was observed in 47%, partial remission in 31%, and progression in 9% of the 45 patients who completed the therapy. Five patients died before completion of 12 months of follow-up. One of the patients died due to myocardial infarction. In one case, the information after 12 months is incomplete. The progression free survival was 37.4 months. During 12 months follow-up, transient decrease of PLT, WBC and haemoglobin values was observed. A transient increase of creatinine level (within normal ranges) and decrease of GFR values were found. Conclusions: NETs 90Y-DOTATATE therapy results in symptomatic relief and tumour mass reduction. The mild critical organ toxicity does not limit the PRRT of NETs. (Pol J Endocrinol 2011; 62 (5): 392&#8211;400

Preclinical pharmacokinetics, biodistribution, radiation dosimetry and toxicity studies required for regulatory approval of a phase I clinical trial with 111In-CP04 in medullary thyroid carcinoma patients

Introduction: From a series of radiolabelled cholecystokinin (CCK) and gastrin analogues, 111In-CP04 (111In-DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) was selected for further translation as a diagnostic radiopharmaceutical towards a first-in-man study in patients with medullary thyroid carcinoma (MTC). A freeze-dried kit formulation for multicentre application has been developed. We herein report on biosafety, in vivo stability, biodistribution and dosimetry aspects of 111In-CP04 in animal models, essential for the regulatory approval of the clinical trial. Materials and methods: Acute and extended single dose toxicity of CP04 was tested in rodents, while the in vivo stability of 111In-CP04 was assessed by HPLC analysis of mouse blood samples. The biodistribution of 111In-CP04 prepared from a freeze-dried kit was studied in SCID mice bearing do

Highlight selection of radiochemistry and radiopharmacy developments by editorial board

Background: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development. Main Body: This commentary of highlights has resulted in 21 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals. Conclusion: Trends in radiochemistry and radiopharmacy are highlighted demonstrating the progress in the research field in various topics including new PET-labelling methods, FAPI-tracers and imaging, and radionuclide therapy being the scope of EJNMMI Radiopharmacy and Chemistry

COST Action CA19114, Network for Optimized Astatine labelled Radiopharmaceuticals

Cancer is a major health concerns for European citizens. Thus, the main research aim of this Network for Optimized Astatine labeled Radiopharmaceuticals (NOAR) COST Action is to successfully demonstrate that one of the most promising radionuclides for Targeted Alpha Therapy (TAT), namely astatine-211, can become the European standard for treatment of certain cancerous pathologies. To this end, an efficient networking is essential among all European stakeholders interested in promoting astatine-211 for medical applications. NOAR COST Action brings together European and international excellence labs, astatine-211 production centers, hospitals, industry and patient associations from more than 20 countries, thus covering the whole value chain of innovation: production, chemistry, radiochemistry, biology, preclinical and clinical research and delivery of radiopharmaceuticals to patients. A European web portal will be created containing information for patients, practitioners, researchers, Industry and as a contact point for National and European patient associations. The idea is to gather forces at the European level in order to implement actions to leverage hurdles to the development of this powerful radionuclide and to identify pathologies in which it will be particularly relevant. A special emphasis will be given to train a new generation of young researchers and PhD students, promoting interdisciplinary competencies through international and inter-sectoral mobility. The long-term goal of this project is to make Astatine-211 technology available to all European citizen