Evaluation of a New 177Lu-Labeled Somatostatin Analog for the Treatment of Tumors Expressing Somatostatin Receptor Subtypes 2 and 5

Mansi, Rosalba; Nicolas, Guillaume; Pozzo, Luigi Del; Abid, Karim; Grouzmann, Eric; Fani, Melpomeni

doi:10.3390/molecules25184155

Cited by 2 publications

(2 citation statements)

References 35 publications

(47 reference statements)

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“…Clinical application of somatostatin has been limited by its very short half-life (<3 min), necessitating continuous intravenous infusion. Hence, a number of SAAs with a longer half-life (1.5–2 h) are applied in radiolabeled somatostatin analogue/peptide receptor radionuclide therapy (PRRT) [ 23 , 25 , 26 , 58 , 217 , 236 , 237 , 238 ]. Moreover, while the native SST binds to all SSTRs, OCT binds with high affinity to SST2 and SST5 [ 239 ].…”

Section: Clinical Application Of the Srif System Componentsmentioning

confidence: 99%

Somatostatin and Its Receptor System in Colorectal Cancer

Kasprzak

2021

Biomedicines

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Somatostatin (SST)/somatotropin release-inhibiting factor (SRIF) is a well-known neuropeptide, widely distributed in the central and peripheral nervous systems, that regulates the endocrine system and affects neurotransmission via interaction with five SST receptors (SST1-5). In the gastrointestinal tract, the main SST-producing cells include intestinal enteroendocrine cells (EECs) restricted to the mucosa, and neurons of the submucosal and myenteric plexuses. The action of the SRIF system is based on the inhibition of endocrine and exocrine secretion, as well as the proliferative responses of target cells. The SST1–5 share common signaling pathways, and are not only widely expressed on normal tissues, but also frequently overexpressed by several tumors, particularly neuroendocrine neoplasms (NENs). Furthermore, the SRIF system represents the only peptide/G protein-coupled receptor (GPCR) system with multiple approved clinical applications for the diagnosis and treatment of several NENs. The role of the SRIF system in the histogenesis of colorectal cancer (CRC) subtypes (e.g., adenocarcinoma and signet ring-cell carcinoma), as well as diagnosis and prognosis of mixed adenoneuroendocrine carcinoma (MANEC) and pure adenocarcinoma, is poorly understood. Moreover, the impact of the SRIF system signaling on CRC cell proliferation and its potential role in the progression of this cancer remains unknown. Therefore, this review summarizes the recent collective knowledge and understanding of the clinical significance of the SRIF system signaling in CRC, aiming to evaluate the potential role of its components in CRC histogenesis, diagnosis, and potential therapy.

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Section: Clinical Application Of the Srif System Componentsmentioning

confidence: 99%

Somatostatin and Its Receptor System in Colorectal Cancer

Kasprzak

2021

Biomedicines

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“…Peptide receptor radionuclide therapy is a cancer treatment option [ 1 ] for patients suffering from unresectable neuroendocrine tumors that express somatostatin receptors [ 2 ]. The treatment consists to intravenously inject somatostatin analogue radiolabelled with Lu ( Lu-DOTATATE).…”

Section: Introductionmentioning

confidence: 99%

Patient-specific dosimetry adapted to variable number of SPECT/CT time-points per cycle for $$^{177}$$Lu-DOTATATE therapy

et al. 2022

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Background The number of SPECT/CT time-points is important for accurate patient dose estimation in peptide receptor radionuclide therapy. However, it may be limited by the patient’s health and logistical reasons. Here, an image-based dosimetric workflow adapted to the number of SPECT/CT acquisitions available throughout the treatment cycles was proposed, taking into account patient-specific pharmacokinetics and usable in clinic for all organs at risk. Methods Thirteen patients with neuroendocrine tumors were treated with four injections of 7.4 GBq of $$^{177}$$ 177 Lu-DOTATATE. Three SPECT/CT images were acquired during the first cycle (1H, 24H and 96H or 144H post-injection) and a single acquisition (24H) for following cycles. Absorbed doses were estimated for kidneys (LK and RK), liver (L), spleen (S), and three surrogates of bone marrow (L2 to L4, L1 to L5 and T9 to L5) that were compared. 3D dose rate distributions were computed with Monte Carlo simulations. Voxel dose rates were averaged at the organ level. The obtained Time Dose-Rate Curves (TDRC) were fitted with a tri-exponential model and time-integrated. This method modeled patient-specific uptake and clearance phases observed at cycle 1. Obtained fitting parameters were reused for the following cycles, scaled to the measure organ dose rate at 24H. An alternative methodology was proposed when some acquisitions were missing based on population average TDRC (named STP-Inter). Seven other patients with three SPECT/CT acquisitions at cycles 1 and 4 were included to estimate the uncertainty of the proposed methods. Results Absorbed doses (in Gy) per cycle available were: 3.1 ± 1.1 (LK), 3.4 ± 1.5 (RK), 4.5 ± 2.8 (L), 4.6 ± 1.8 (S), 0.3 ± 0.2 (bone marrow). There was a significant difference between bone marrow surrogates (L2 to L4 and L1 to L5, Wilcoxon’s test: p value < 0.05), and while depicting very doses, all three surrogates were significantly different than dose in background (p value < 0.01). At cycle 1, if the acquisition at 24H is missing and approximated, medians of percentages of dose difference (PDD) compared to the initial tri-exponential function were inferior to 3.3% for all organs. For cycles with one acquisition, the median errors were smaller with a late time-point. For STP-Inter, medians of PDD were inferior to 7.7% for all volumes, but it was shown to depend on the homogeneity of TDRC. Conclusion The proposed workflow allows the estimation of organ doses, including bone marrow, from a variable number of time-points acquisitions for patients treated with $$^{177}$$ 177 Lu-DOTATATE.

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Evaluation of a New 177Lu-Labeled Somatostatin Analog for the Treatment of Tumors Expressing Somatostatin Receptor Subtypes 2 and 5

Cited by 2 publications

References 35 publications

Somatostatin and Its Receptor System in Colorectal Cancer

Somatostatin and Its Receptor System in Colorectal Cancer

Patient-specific dosimetry adapted to variable number of SPECT/CT time-points per cycle for $$^{177}$$Lu-DOTATATE therapy

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