Dataset Information

Application and Dosimetric Requirements for Gallium-68-labeled Somatostatin Analogues in Targeted Radionuclide Therapy for Gastroenteropancreatic Neuroendocrine Tumors.

ABSTRACT: Neuroendocrine tumors (NETs) are associated with variable prognosis, with grade 1 and 2 NETs having more favorable outcomes than grade 3. Patients with gastroenteropancreatic (GEP)-NET need individualized interdisciplinary evaluations and treatment. New treatment options have become available with significant improvements in progression-free survival. Peptide receptor radionuclide therapy (PRRT) using (90)Y or (177)Lu-labeled somatostatin analogues (SSTa) has also shown promise in the treatment of advanced progressive NETs. (68)Ga-1,4,7,10-tetraazacyclodecane-1,4,7,10-tetraacetic acid (DOTA)-SSTa can be used as companion imaging agents to assist in radionuclide therapy selection. (68)Ga-DOTA-SSTa PET/computed tomography might also provide information for prognosis, tumor response assessment to PRRT, and internal dosimetry.

SUBMITTER: Taieb D

PROVIDER: S-EPMC4617555 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Application and Dosimetric Requirements for Gallium-68-labeled Somatostatin Analogues in Targeted Radionuclide Therapy for Gastroenteropancreatic Neuroendocrine Tumors.

Taïeb David D Garrigue Philippe P Bardiès Manuel M Abdullah Ahmad Esmaeel AE Pacak Karel K

PET clinics 20150708 4

Neuroendocrine tumors (NETs) are associated with variable prognosis, with grade 1 and 2 NETs having more favorable outcomes than grade 3. Patients with gastroenteropancreatic (GEP)-NET need individualized interdisciplinary evaluations and treatment. New treatment options have become available with significant improvements in progression-free survival. Peptide receptor radionuclide therapy (PRRT) using (90)Y or (177)Lu-labeled somatostatin analogues (SSTa) has also shown promise in the treatment ...[more]

PMID: 26384594

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Project description:PurposeEvaluate patients' and nurses' experiences, including injection problem frequency, with the somatostatin analogues (SSAs) lanreotide autogel® (Somatuline® autogel®, deep subcutaneous) and octreotide long-acting release (LAR) (Sandostatin® LAR®, intramuscular) when treating gastroenteropancreatic neuroendocrine tumors (GEP-NETs).MethodsAn observational, cross-sectional study across 2 NET centers in Sweden. Questionnaires based on participants' most recent injection experience were sent to patients with GEP-NETs treated with octreotide or lanreotide, and to nurses administering these treatments. Nurses were identified via patients completing their questionnaires. Resource use was sourced from Swedish prescription registry records. The planned sample size was 200, based on an estimated proportion of 0.50 and ±7% precision.Results119/156 patients (n=53, lanreotide; n=66, octreotide) and 43/53 nurses (n=22, lanreotide; n=21, octreotide) completed questionnaires. Despite smaller recruitment than planned, the endpoint precision was ±9% with 119 participants, and still considered reasonable. More octreotide-treated patients reported problems (18% vs none; P=0.001) and experienced moderate-to-high anxiety pre-injection (11% vs 2%). Patients had similar physical HRQoL scores overall (Short Form-12 mean composite scores: physical: 39.4 vs 37.6; mental: 50.7 vs 49.6). The mean number of lanreotide and octreotide doses dispensed per year were 11.1 and 12.6, respectively (P<0.05). In the lanreotide group, 28% self-injected, while 29% were not aware they could self-inject. In the octreotide group, 3% self-injected and 73% were unaware of the availability of an SSA for self-injection. Most patients (61%) felt well-informed about their disease and treatment. Nurses were generally experienced and felt confident and well-informed about giving SSA injections; however, only 12% felt well-informed about the disease and treatment.ConclusionThose treated with lanreotide reported fewer injection problems and experienced less pre-injection anxiety than those treated with octreotide. SSA choice did not appear to affect patients' HRQoL. Some patients treated with octreotide were unaware of an SSA with the flexibility of self-injection.

Project description:ImportanceNeuroendocrine tumors (NETs) express somatostatin receptors, which can be targeted with radiolabeled peptides. In a variety of solid tumors, radioguided surgery (RGS) has been used to guide surgical resection. Gallium 68 (68Ga) dota peptides have been shown to be more accurate than other radioisotopes for detecting NETs. A pilot study previously demonstrated the feasibility and safety of 68Ga-dotatate RGS for patients with NETs.ObjectiveTo evaluate what intraoperative techniques and thresholds define positive lesions that warrant resection during 68Ga-dotatate RGS.Design, setting, and participantsThis prospective cohort study, conducted between October 23, 2013, and February 14, 2018, included 44 patients with NETs who underwent 68Ga-dotatate RGS.InterventionGallium 68-dotatate RGS.Main outcomes and measuresThe in vivo and ex vivo tumor to background ratio (TBR) was assessed for resected lesions and correlated with the histopathologic findings.ResultsForty-four patients (22 women and 22 men; mean [SD] age, 51.0 [13.7] years) had 133 lesions detected on preoperative imaging scans, with a diagnosis of a pancreatic NET (19 of 44 [43%]), gastrointestinal NET (22 of 44 [50%]), and pheochromocytoma or paraganglioma (3 of 44 [7%]). The TBR was obtained by normalizing to the omentum (106 of 133 [79.7%]) or other solid organs (27 of 133 [20.3%]). The omentum had a significantly lower mean (SD) count than other solid organs for background count activity 3 hours after injection (22.1 [17.0] vs 34.5 [39.0]; P < .001). The lesions containing NETs had a higher TBR than those that did not contain NETs (18.9 vs 4.4; P < .001). On a receiver operating characteristic curve analysis, a TBR of 2.5 had a sensitivity of 90% and a specificity of 25%, and a TBR of 16 had a sensitivity of 54% and a specificity of 81%.Conclusions and relevanceA TBR of 2.5 or greater is a highly sensitive threshold for indicating a lesion to be consistent with a NET on histologic findings and thus warranting surgical resection. The omentum should be used as the background count activity for 68Ga-dotatate RGS for patients with abdominal NETs.

Project description:BackgroundGastroenteropancreatic neuroendocrine tumors (GEP-NETs) are increasingly common malignancies and tend to have favorable long-term prognoses. Somatostatin analogues (SSA) are a first-line treatment for many NETs. Short-term experiments suggest an association between SSAs and hyperglycemia. However, it is unknown whether there is a relationship between SSAs and clinically significant hyperglycemia causing development of diabetes mellitus (DM), a chronic condition with significant morbidity and mortality.AimIn this study, we aimed to compare risk of developing DM in patients treated with SSA vs no SSA treatment.Methods and resultsUsing the Surveillance, Epidemiology, and End Results (SEER) database and linked Medicare claims (1991-2016), we identified patients age 65+ with no prior DM diagnosis and a GEP-NET in the stomach, small intestine, appendix, colon, rectum, or pancreas. We used χ2 tests to compare SSA-treated and SSA-untreated patients and multivariable Cox regression to assess risk factors for developing DM. Among 8464 GEP-NET patients, 5235 patients had no prior DM and were included for analysis. Of these, 784 (15%) patients received SSAs. In multivariable analysis, the hazard ratio of developing DM with SSA treatment was 1.19, which was not statistically significant (95% CI 0.95-1.49). Significant risk factors for DM included black race, Hispanic ethnicity, prior pancreatic surgery, prior chemotherapy, tumor size >2 cm, pancreas tumors, and higher Charlson scores.ConclusionDM was very common in GEP-NET patients, affecting 53% of our cohort. Despite prior studies suggesting an association between SSAs and hyperglycemia, our analysis found similar risk of DM in SSA-treated and SSA-untreated GEP-NET patients. Further studies are needed to better understand this relationship. As NET patients have increasingly prolonged survival, it is crucial to identify chronic conditions such as DM that these patients may be at elevated risk for.

Project description:BackgroundSiderophores are small iron-binding molecules produced by microorganisms to facilitate iron acquisition from the environment. Radiolabelled siderophores offer a promising solution for infection imaging, as they can specifically target the pathophysiological mechanisms of pathogens. Gallium-68 can replace the iron in siderophores, enabling molecular imaging with positron emission tomography (PET). Stereospecific interactions play a crucial role in the recognition of receptors, transporters, and iron utilisation. Furthermore, these interactions have an impact on the host environment, affecting pharmacokinetics and biodistribution. This study examines the influence of siderophore stereoisomerism on imaging properties, with a focus on ferrirubin (FR) and ferrirhodin (FRH), two cis-trans isomeric siderophores of the ferrichrome type.ResultsTested siderophores were labelled with gallium-68 with high radiochemical purity. The resulting complexes differed in their in vitro characteristics. [68Ga]Ga-FRH showed less hydrophilic properties and higher protein binding values than [68Ga]Ga-FR. The stability studies confirmed the high radiochemical stability of both [68Ga]Ga-siderophores in all examined media. Both siderophores were found to be taken up by S. aureus, K. pneumoniae and P. aeruginosa with similar efficacy. The biodistribution tested in normal mice showed rapid renal clearance with low blood pool retention and fast clearance from examined organs for [68Ga]Ga-FR, whereas [68Ga]Ga-FRH showed moderate retention in blood, resulting in slower pharmacokinetics. PET/CT imaging of mice injected with [68Ga]Ga-FR and [68Ga]Ga-FRH confirmed findings from ex vivo biodistribution studies. In a mouse model of S. aureus myositis, both radiolabeled siderophores showed radiotracer accumulation at the site of infection.ConclusionsThe 68Ga-complexes of stereoisomers ferrirubin and ferrirhodin revealed different pharmacokinetic profiles. In vitro uptake was not affected by isomerism. Both compounds had uptake with the same bacterial culture with similar efficacy. PET/CT imaging showed that the [68Ga]Ga-complexes accumulate at the site of S. aureus infection, highlighting the potential of [68Ga]Ga-FR as a promising tool for infection imaging. In contrast, retention of the radioactivity in the blood was observed for [68Ga]Ga-FRH. In conclusion, the stereoisomerism of potential radiotracers should be considered, as even minor structural differences can influence their pharmacokinetics and, consequently, the results of PET imaging.

Dataset Information

Application and Dosimetric Requirements for Gallium-68-labeled Somatostatin Analogues in Targeted Radionuclide Therapy for Gastroenteropancreatic Neuroendocrine Tumors.

Publications

Application and Dosimetric Requirements for Gallium-68-labeled Somatostatin Analogues in Targeted Radionuclide Therapy for Gastroenteropancreatic Neuroendocrine Tumors.

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