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Radiopharmaceuticals for Diagnostics
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Jim Ballinger, Jacek Koziorowski
Neuroendocrine tumours (NETs) arise from the neuroendocrine system and include gastrointestinal, lung, and pancreatic NETs. NETs overexpress the somatostatin receptor, which can be imaged with tracers that are ligands for the receptor, including 111In-pentetreotide (DTPA-octreotide, Octreoscan) and 99mTc-hynic-TOC (EDDA/hynic-Tyr3-octreotide, Tektrotyd). Planar and/or SPECT/CT images are acquired at 24 h with 111In and at 1-2 and 4 h with 99mTc [38, 39]. Analogues of pentetreotide coupled to beta-emitting radionuclides are used for therapy of NETs, most notably 177Lu-DOTATATE (DOTA-Tyr3-octreotate, Lutathera) [40]. Diagnostic scans are important for selection of patients for therapy and for monitoring response to therapy. In particular, 68Ga-DOTATATE (DOTA-Tyr3-octreotate, NETSPOT) is becoming widely used. 68Ga (t½ 68 min) is obtained on-site from a generator loaded with 68Ge (t½ 271 days). 68Ga-DOTATATE was originally prepared with an automated synthesis device followed by purification but now a ‘kit’ formulation is available that requires only heating in a vial with no further purification.
Targeted Molecular Radiotherapy – Clinical Considerations and Dosimetry*
Published in W. P. M. Mayles, A. E. Nahum, J.-C. Rosenwald, Handbook of Radiotherapy Physics, 2021
The optimal frequency of administration for various therapy procedures is a matter of ongoing debate and can vary widely. Radioiodine may be administered at intervals of 6–8 months in high-risk patients with continuing disease, often until complete response is achieved or until the disease becomes iodine negative. PRRT with 90Y-DOTATATE is often given just twice, 6–8 weeks apart, although 177Lu–PSMA (Lutathera) is administered according to the company's protocol i.e. four times at 6-week intervals. An academic study of high-activity 186Re-HEDP was carried out with a single high-activity administration, with peripheral stem-cell support; the mean survival was 20.1 months for patients who received over 3.5 GBq (Denis-Bacelar et al. 2017). Conversely, 223Ra is administered six times at monthly intervals at low levels to minimise toxicity.
Clinical efficacy of first and second series of peptide receptor radionuclide therapy in patients with neuroendocrine neoplasm: a cohort study
Published in Scandinavian Journal of Gastroenterology, 2021
M. D. Zacho, P. Iversen, G. E. Villadsen, S. M. D. Baunwall, A. K. Arveschoug, H. Grønbaek, G. Dam
The treatment regimens have changed over time. From 2008 to 2015 the standard regimen was treatment with 90Y-DOTATOC, and we adopted the treatment regimens from Basel [21]. From 2015 the standard regimen was treatment with 177Lu-DOTA-peptide (both in house produced 77Lu-DOTATOC and 77Lu-DOTATE (Lutathera) acquired ready for use) performed according to the EANM guidelines [18]. Combination treatment was used from 2015 in patients with G3-tumors and/or bulky tumors. The standard dose of 177Lu-DOTA-peptidewas 7.4GBq. From 2008 to 2012 the standard dose of 90Y-DOTATOC was 3.7GBq/m2 body surface (a maximum doses of 7.4GBq/injection), distributed over two treatments with an interval of 8–10 weeks. In 2013, this was changed to four treatments (with an interval of 8–10 weeks) with a standard dose at 1.85GBq/m2 body surface (maximum 3.7GBq/injection) [12,22]. The decision to re-treat patients with a second or third cycle was primarily based on a combination of the duration of response, toxicity and degree of uptake on SSTR-PET. Patients who developed progression within 12 months were excluded from retreatment.
Theranostic approaches in nuclear medicine: current status and future prospects
Published in Expert Review of Medical Devices, 2020
Luca Filippi, Agostino Chiaravalloti, Orazio Schillaci, Roberto Cianni, Oreste Bagni
The demonstration of SSTRs in NET opened the door to targeted radionuclide therapy based on the administration of synthetic analogs of somatostatin labeled with beta-emitting radioisotopes, especially 90Y and 177Lu. This theranostic approach is known as peptide radionuclide receptor therapy (PRRT). Lutathera® (177Lu-DOTATATE) has been approved in January 2018 by Food and Drug Administration (FDA) and in September 2017 in Europe by European Medicines Agency (EMA) as the first radiopharmaceutical for PRRT in progressive gastroenteropancreatic NET. It consists in the administration of 177Lu-DOTATATE, fractioned in four cycles of fixed activity of 7.4 GBq at the interval of 8 weeks [43]. The approval of Lutathera® was preceded by a huge number of clinical studies aimed to assess the efficacy and safety of PRRT in the last 20 years.
Radioactive polymeric nanoparticles for biomedical application
Published in Drug Delivery, 2020
Shentian Wu, Edward Helal-Neto, Ana Paula dos Santos Matos, Amir Jafari, Ján Kozempel, Yuri José de Albuquerque Silva, Carolina Serrano-Larrea, Severino Alves Junior, Eduardo Ricci-Junior, Frank Alexis, Ralph Santos-Oliveira
Polymeric radioactive nanoparticles have showed to be promising for translational studies. Although it has showed to have high efficacy, it haven’t presented many commercial forms when compared to traditional radiopharmaceuticals. However, Health institutes as NIH and NCI have been founding diverse clinical trials to study radioactive nanoparticles, including polymerics, for image and therapeutic uses (Zakeri et al., 2019). In 2017, FDA Approves Novel Radio-peptide Targeted Therapy Clinical Trial for Neuroendocrine Cancer (Hennrich and Kopka, 2019). Lutathera® combines the radionuclide 177Lu with the somatostatin analogue DOTA-TATE to deliver ionizing radiation specifically to tumor cells expressing somatostatin receptors. desferrioxamine-based BFCAs for 89Zr have been reported with improved stability that permits reliable in vivo evaluation of polymeric materials (Deri et al., 2014; Pant et al., 2017). Several studies have investigated radioactive-iodine-labeled functional nanomaterials for cancer treatment. Liu et al. used albumin nanoparticles containing paclitaxel (PTX), a potent chemotherapeutic drug. This material showed prolonged blood circulation time, specific tumor uptake, and high intratumor penetration ability. The combined therapeutic effects (chemo- and radiotherapy) of 131I-HSA-PTX were found to be highly effective in the 4T1 cancer xenograft model compared to radiotherapy- and chemotherapy-alone groups (Tian et al., 2017).