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Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumours
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Anna Sundlöv, Katarina Sjögreen Gleisner
The advent of the radiolabelled synthetic SSAs led to the development of the diagnostic nuclear medicine method of somatostatin receptor scintigraphy using 111In (Indium). Since 111In emits Auger electrons in its radioactive decay, it can potentially be used for therapeutic purposes. The first trials in humans with high injected activities of 111In-pentreotide demonstrated a small but encouraging therapeutic effect [6]. Currently, SSTR scintigraphy is rapidly being replaced by SSTR PET/CT using 68Ga (Gallium)-labelled DOTA-TOC or DOTA-TATE, which is used not only for staging of NET, but also for selection of patients for PRRT (Figure 1). For therapeutic purposes, the real breakthrough was the development of DOTA-chelated, beta-emitter labelled compounds such as 90Y-DOTA-TOC and 177Lu-DOTA-TATE, the latter being the compound that has reached the widest clinical use. The safety and efficacy of 177Lu-DOTA-TATE vis a vis standard therapy (high-dose octreotide) was demonstrated in the phase III trial NETTER-1: The patients in the PRRT arm reached a median progression-free survival (mPFS) of 28 months, whereas those in the control arm had a mPFS of only 8 months [7]. Based on these results, PRRT with 177Lu-DOTA-TATE was approved by the European Medicines Agency and the US Food and Drug Administration for the treatment of gastro-entero-pancreatic NETs.
Targeted Molecular Radiotherapy – Clinical Considerations and Dosimetry*
Published in W. P. M. Mayles, A. E. Nahum, J.-C. Rosenwald, Handbook of Radiotherapy Physics, 2021
Radiopeptides target somatostatin receptors expressed on the surface of neuroendocrine tumours, typically the somatostatin receptor subtype 2. This therapeutic modality is rapidly increasing as a treatment option for neuroendocrine cancers, particularly with the development of 177Lu- and 90Y-DOTATATE (Bodei et al. 2008).
Primary adrenal malignancy
Published in Anju Sahdev, Sarah J. Vinnicombe, Husband & Reznek's Imaging in Oncology, 2020
Ayshea Hameeduddin, Anju Sahdev, Rodney H Reznek
PCs and PGLs express somatostatin receptors and therefore can be detected using the PET tracer 68Ga when labelled to one of three somatostatin analogues (DOTA-TATE, DOTA-TOC, and DOTA-NOC) (Figure 14.14). In one retrospective series comparing 18FDG PET-CT with 68Ga-DOTATATE and MIBG in 23 patients with known PCs/PGL, the authors found that both PET tracers had similar sensitivity for detecting lesions; however, 68Ga-DOTATE demonstrated higher tracer uptake in the lesions, allowing for better lesion-background contrast and easier detection, improving the detection of small metastatic lesions. 68Ga-PET-CT also detected more bone lesions than 18FDG and MIBG which is supported by other studies (88,90,91). Detection of disease with 68Ga-PET-CT enables therapeutic options with 177Lu and 90Y, as mentioned previously.
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).
Clinico-radiological findings of neuroendocrine tumour metastases to the orbit
Published in Orbit, 2022
T G Ryan, V Juniat, C Stewart, R Malhotra, T G Hardy, A A McNab, G Davis, D Selva
Functional imaging utilising tracers for somatostatin receptors commonly found on neuroendocrine tumour cell membranes, e.g., 68Ga-DOTATATE PET/CT, has advanced methods to stage this disease, to identify metastasis and monitor response to treatment.2,6–8 However, ophthalmologists are most likely to encounter neuroendocrine tumour metastases on computerised tomography (CT) or magnetic resonance imaging (MRI) in the context of patients presenting with orbital symptoms, with or without a previous history of primary neuroendocrine tumours. We present a case series and review the current literature on the clinico-radiological findings for neuroendocrine tumour metastases to the orbit.
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
A few case studies have shown success in treating NEPC with 177 DOTA-TATE Lutetium following treatment with 177 PSMA Lutetium. Lutetium DOTA-TATE was FDA approved in 2018 for the treatment of SR positive gastroenteropancreatic neuroendocrine tumor and is effective in improving PFS in these patients [92,93]. In one case study a patient treated with 7 cycles of 177 PSMA Lutetium for CRPC had post-treatment PSA rise with stable Ga PSMA PET/CT scan. NE differentiation was suspected, and 68 Ga-DOTA-TATE PET/CT showed multiple somatostatin-avid lesions throughout the skeleton. The patient was subsequently treated with 177 DOTA-TATE Lutetium, had a transient reduction in bone pain and a 24% drop in PSA, but was unable to receive a 2nd treatment cycle due to severe fatigue [62]. In another case study a patient with pathologically confirmed PC with neuroendocrine differentiation had temporary remission with 177 PSMA lutetium. After disease progression and severe bone pain the patient underwent 2 cycles of 177 DOTA-TATE Lutetium and had complete pain relief within 1 week of the first cycle. Post-treatment scan showed partial radiographic remission, and significant decreases in PSA (83.92 ng/ml to 0.89 ng/ml), ALP (375 IU/L to 108 IU/L), and CgA (110.44 ng/mL to 44.82 ng/mL) [94]. A third case study showed a patient with continued bone pain after 4 cycles of 177 PSMA lutetium for CRPC and a CgA level 8 times the upper limit of normal had multiple somatostatin-avid bony metastasis on 99 m Tc-octreotide scintigraphy, discordant with previous 68 Ga-PSMA and post-177Lu-PSMA images. NEPC was confirmed with pathology and subsequent treatment with 177 lutetium DOTA-TATE led to reduced bone pain and normalization of CgA, though post treatment imaging revealed continued metastatic lesions [63].