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Translation of Radiopharmaceuticals
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Pedro Fragoso Costa, Latifa Rbah-Vidal, An Aerts, Fijs W.B. van Leeuwen, Margret Schottelius
Paradigmatically exemplified by the clinical success of using the somatostatin receptor (sst) ligands DOTATOC and DOTATATE, both for imaging (labelled with 68Ga) and RLT (labelled with 177Lu or 90Y) of neuroendocrine tumours, the term “theranostics” is oftentimes reduced to the very narrow definition of “using the same radiolabelling precursor for different clinical applications, that is, diagnosis and subsequent RLT.”
Therapeutic Potential of Radiolabeled Peptides: The Basel Experience
Published in Marco Chinol, Giovanni Paganelli, Radionuclide Peptide Cancer Therapy, 2016
Christian Waldherr, Jan Müller-Brand
The use of a combination of 90Y- and 177Lu-labeled DOTATOC as well as the combination of standard radiosensitizing chemotherapy regimen plus 90Y-and 177Lu-labeled DOTATOC is supposed to improve future results significantly (25). Trials are in preparation at Basel and elsewhere. Special care has to be taken of patients who were pretreated with the standard agent streptozotocin, which is known to be nephrotoxic (26).
Non-FDG radionuclide imaging and targeted therapies
Published in Anju Sahdev, Sarah J. Vinnicombe, Husband & Reznek's Imaging in Oncology, 2020
Luigi Aloj, Ferdia A Gallagher
Somatostatin receptor-targeted radionuclide therapy for neuroendocrine tumours started developing shortly after the introduction of imaging applications. Initial experiences were based on compassionate use or small case series from individual centres with high doses of 111In-octreotide, the same agent approved for imaging. It was believed that the auger electron emission of 111In could deliver toxic radiation doses to receptor-expressing tumours. The approach was appealing, but it did not result in significant clinical impact. This initial experience was rapidly followed up by early clinical trials with 90Y-labelled DOTATOC. 90Y is a high-energy beta emitter which had been recognized as having suitable properties for radionuclide therapy. It was utilized in several centres in Europe in the late 1990s and demonstrated efficacy in multiple small patient series (26). The search for a radionuclide with more suitable physical characteristics for therapy and the concern of significant kidney and bone marrow toxicity of 90Y led to the use of 177Lu. This radionuclide has a longer half-life than 90Y (6.7 days vs. 2.7 days) and lower energy beta emission (Emax 490 KeV vs. 2.2 MeV), resulting in longer radiation delivery and lower particle penetration. 177Lu also has the advantage of a low-abundance gamma emission (11%, 211 KeV) which makes it suitable for high-quality imaging with SPECT, which cannot be obtained with 90Y. Several centres started utilizing 177Lu DOTATATE in the 2000s for systemic treatment of metastatic neuroendocrine tumours, particularly midgut carcinoids, showing impressive response rates in a class of tumours where systemic chemotherapy had shown very little success (27). The toxicity profile of 177Lu-DOTATATE proved to be favourable compared to 90Y-DOTATOC. In 2011 an industry-sponsored phase 3 trial known as NETTER-1 was initiated in patients with midgut neuroendocrine tumours showing prolonged progression-free survival and higher response rate in patients in the 177Lu-DOTATATE treatment arm relative to the control group (28). This trial led to approval by the FDA and EMA in 2017 for the treatment of midgut neuroendocrine tumours. An example of the theranostic applications of somatostatin receptor targeting is given in Figure 44.4.
Peptide receptor radionuclide therapy in neuroendocrine neoplasms and related tumors: from fundamentals to personalization and the newer experimental approaches
Published in Expert Review of Precision Medicine and Drug Development, 2023
A number of large clinical studies have reported the toxicity profile of PRRT in the literature, few prominent ones are summarized in Table 5). Kidneys are the dose-limiting organs in PRRT and active renal protection protocols are followed in the clinics, though still there are uncommon occurrences of renal compromise due to PRRT. Valkema et al reported a creatinine clearance loss of about 3.8% per year for 177Lu-DOTATATE and 7.3% per year for 90Y-DOTATOC therapy. As summarized below different studies have reported severe grade toxicity (i.e. grades III and IV) ranging from 0.6 to 9%. Many of these patients were having preexisting renal compromise due to long-standing diabetes, hypertension, or obstructive nephropathies [60].
Nordic 2023 guidelines for the diagnosis and treatment of lung neuroendocrine neoplasms
Published in Acta Oncologica, 2023
Gitte Dam, Henning Grønbæk, Anna Sundlöv, Johan Botling, Anders Sundin, Rene Horsleben Petersen, Staffan Welin, Espen-Thiis Evensen, Halfdan Sorbye, Elizaveta Tabaksblat, Anne Kirstine Arveschoug, Jann Mortensen, Andreas Kjaer, Ulrich Knigge, Eva Tiensuu Janson, Seppo W. Langer
Tumor staging according to TNM is based on intravenously (IV) contrast-enhanced chest-CT and CT or magnetic resonance imaging (MRI) of the abdomen. This is performed in combination with somatostatin receptor imaging (SRI). PET is usually performed as a PET/CT [11] and 68Ga-DOTATOC versus -TATE have comparable diagnostic accuracy. 64Cu-DOTATATE may have advantages over 68Ga-DOTATOC in the detection of lesions, but the patient-based sensitivity is the same. Contrast-enhanced MRI of the liver, especially with a hepatocyte-specific contrast medium and including diffusion-weighted imaging (DWI), is preferable to contrast-enhanced CT because of the considerably higher sensitivity for detection of liver metastases on MRI [12]. The use of 18F-fluoro-deoxy-glucose (FDG)-PET/CT in lung-NEN has been debated. However, recently FDG-PET/CT was found to be positive in 81-93% of TC and 86-96% of AC [13,14]. For patients in whom peptide receptor radionuclide therapy (PRRT) is considered, FDG-PET/CT may add value for the identification of possible mismatched lesions (FDG positive, SRI negative).
Addressing the need for more therapeutic options in neuroendocrine prostate cancer
Published in Expert Review of Anticancer Therapy, 2023
Jayson Kemble, Eugene D. Kwon, R. Jeffrey Karnes
Somatostatin receptor (SR) overexpression is seen in a variety of neuroendocrine tumors, and imaging with somatostatin analogs such as 68 Ga-DOTA-TOC, 68 Ga-DOTA-NOC, and 68 Ga-DOTA-TATE have shown efficacy in identifying neuroendocrine tumor differentiation [41,54–57]. SR overexpression has been detected in CRPC, with one study reporting moderately high to high uptakes (SUV max >5) of 68 Ga-DOTA-TATE in 6 of 12 patients with CRPC, but loss of this receptor is associated with an aggressive cancer phenotype with a shorter OS [27,58–60]. It is unclear how often SR is overexpressed in NEPC. In a large set of PC samples, only 1 out of 49 samples with a CgA Immunoreactivity score (IRS) ≥ 6 had an IRS ≥ 6 for SR, while 14 samples were devoid of any SR expression [61]. In contrast multiple case studies have described identifying NEPC with a somatostatin analog when other imaging modalities failed to do so [62–67].