Octreoscan Versus FDG-PET for Neuroendocrine Tumor Staging: A Biological Approach

Squires, Malcolm H.; Adsay, Volkan; Schuster, David M.; Russell, Maria C.; Cardona, Kenneth; Delman, Keith A.; Winer, Joshua H.; Altinel, Deniz; Sarmiento, Juan M.; El‐Rayes, Bassel F.; Hawk, Natalyn; Staley, Charles A.; Maithel, Shishir K.; Kooby, David A.

doi:10.1245/s10434-015-4471-x

Cited by 100 publications

(65 citation statements)

References 26 publications

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“…In particular, OCT appears more sensitive than 18 F-FDG for well-differentiated tumors, whereas 18 F-FDG demonstrates superior sensitivity for undifferentiated lesions [57]. In this sense, being patients positive at 18 F-FDG inoperable, there is no role for RGS with 18 F-FDG in patients with NETs.…”

Section: Reviewmentioning

confidence: 98%

Radioguided surgery with radiolabeled somatostatin analogs: not only in GEP-NETs

2017

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Section: Reviewmentioning

confidence: 98%

Radioguided surgery with radiolabeled somatostatin analogs: not only in GEP-NETs

2017

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“…However, given that these tumors frequently overexpress SSTR2, they often clinically respond to synthetic somatostatin analogs such as octreotide and lanreotide (16)(17)(18)(19). Indeed, diagnostic imaging studies of SSTR targets are standard for so-called "octreotide-avid" tumors (20), and peptidebased receptor radionuclide therapy also has been used to clinical effect (21). Thus, we reasoned that octreotide-targeted cellular transduction would enable the expression of tumor necrosis factor (TNF) within the SSTR2-expressing tumor cells after systemic administration through the vulnerable tumor-associated blood vessels of pancreatic NETs without off-target vascular or parenchymal toxicity to normal organs.…”

Section: Significancementioning

confidence: 99%

AAVP displaying octreotide for ligand-directed therapeutic transgene delivery in neuroendocrine tumors of the pancreas

Smith

Yuan

Cardó-Vila

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Patients with inoperable or unresectable pancreatic neuroendocrine tumors (NETs) have limited treatment options. These rare human tumors often express somatostatin receptors (SSTRs) and thus are clinically responsive to certain relatively stable somatostatin analogs, such as octreotide. Unfortunately, however, this tumor response is generally short-lived. Here we designed a hybrid adeno-associated virus and phage (AAVP) vector displaying biologically active octreotide on the viral surface for ligand-directed delivery, cell internalization, and transduction of an apoptosis-promoting tumor necrosis factor (TNF) transgene specifically to NETs. These functional attributes of AAVP-TNF particles displaying the octreotide peptide motif (termed Oct-AAVP-TNF) were confirmed in vitro, in SSTR type 2-expressing NET cells, and in vivo using cohorts of pancreatic NET-bearing Men1 tumor-suppressor gene KO mice, a transgenic model of functioning (i.e., insulin-secreting) tumors that genetically and clinically recapitulates the human disease. Finally, preclinical imaging and therapeutic experiments with pancreatic NET-bearing mice demonstrated that Oct-AAVP-TNF lowered tumor metabolism and insulin secretion, reduced tumor size, and improved mouse survival. Taken together, these proof-of-concept results establish Oct-AAVP-TNF as a strong therapeutic candidate for patients with NETs of the pancreas. More broadly, the demonstration that a known, short, biologically active motif can direct tumor targeting and receptor-mediated internalization of AAVP particles may streamline the potential utility of myriad other short peptide motifs and provide a blueprint for therapeutic applications in a variety of cancers and perhaps many nonmalignant diseases as well.

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“…SRS with 111 In-DPTA-SPECT/CT has also been compared to 18 F-FDG-PET/CT in studies[81, 82, 86]. Similar, although less dramatic results compared with those seen with the comparison of 68 Ga-DOTA-PET/CT and 18 F-FDG-PET/CT reviewed above, were obtained.…”

Section: Molecular Imaging Of Neuroendocrine Tumorsmentioning

confidence: 69%

“…In one study patients with a positive 18 F-FDG-PET/CT with a SUV ratio of 2.5 of greater had a 4-yr survival rate of 0%[81]. Furthermore, in a number of studies, some patients with G1/G2 tumors had positive 18 F-FDG-PET/CT uptake which had important predictive value[33•, 77, 82]. A number of studies have concluded that the results of 18 F-FDG-PET/CT and 68 Ga-DOTA-peptide-PET/CT in patients with NETs are complementary in providing different information that is clinically relevant[77, 79, 80].…”

Section: Molecular Imaging Of Neuroendocrine Tumorsmentioning

confidence: 99%

Molecular imaging in neuroendocrine tumors: recent advances, controversies, unresolved issues, and roles in management

Ito¹,

Jensen²

2017

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

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Purpose To review recent advances in molecular imaging of neuroendocrine tumors (NETs), discuss unresolved issues, and review how these advances are affecting clinical management. Recent findings Molecular imaging of NETs underwent a number of important changes in the last few years, leading to some controversies, unresolved issues, and significant changes in clinical management. The most recent changes are reviewed in this article. Particularly important is the rapid replacement in somatostatin receptor scintigraphy (SRS) of 111In-DTPA-SPECT/CT by 68Ga-DOTA-peptide-PET/CT imaging, which is now approved in many countries including the US. Numerous studies in many different types of NETs demonstrate the greater sensitivity of 68Ga-DOTA-peptide-PET/CT, its high specificity, and its impact on management. Other important developments in SRS/molecular imaging include demonstrating the prognostic value of both 68Ga-DOTA-peptide-PET/CT and 18F-FDG –PET/CT; how their use can be complementary; comparing the sensitivities and usefulness of 68Ga-DOTA-peptide-PET/CT and 18F-FDOPA PET/CT; introducing new linkers and radiolabeled ligands such as 64Cu-DOTA-peptides with a long half-life, enhancing utility; and the introduction of somatostatin receptor antagonists which show enhanced uptake by NETs. In addition, novel ligands which interact with other receptors (GLP1, Bombesin, CCK, GIP, integrin, chemokines) are described which show promise in the imaging of both NETs and other tumors. Summary Molecular imaging is now required for all aspects of the management of patients with NETs. It results are essential not only for the proper diagnostic management of the patient, but also for assessing whether the patient is a candidate for peptide receptor radionuclide therapy (PRRT) with 177Lu and also for providing prognostic value.

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Octreoscan Versus FDG-PET for Neuroendocrine Tumor Staging: A Biological Approach

Cited by 100 publications

References 26 publications

Radioguided surgery with radiolabeled somatostatin analogs: not only in GEP-NETs

Radioguided surgery with radiolabeled somatostatin analogs: not only in GEP-NETs

AAVP displaying octreotide for ligand-directed therapeutic transgene delivery in neuroendocrine tumors of the pancreas

Molecular imaging in neuroendocrine tumors: recent advances, controversies, unresolved issues, and roles in management

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