Clinical Application of 18F-AlF-NOTA-Octreotide PET/CT in Combination With 18F-FDG PET/CT for Imaging Neuroendocrine Neoplasms

Objectives The study is to evaluate biodistribution, dosimetry, safety, and clinical usefulness of 18F-AlF-NOTA-octreotide (18F-OC) PET/CT in combination with 18F-FDG PET/CT for detection of neuroendocrine neoplasms (NENs). Methods The biodistribution, dosimetry, and safety of 18F-OC were evaluated in 3 healthy volunteers. Twenty-two NEN patients underwent PET/CT at 60 minutes after intravenous injection of 3.7 to 4.44 MBq (0.1–0.12 mCi) per kilogram of body weight of 18F-OC. This was followed by 18F-FDG PET/CT within a 2-week period. Results 18F-OC was well tolerated by all healthy volunteers and NEN patients. The calculated effective dose of 18F-OC was 0.023 ± 0.002 mSv/MBq. In NEN patients, we observed prominent 18F-OC tumor uptake and high tumor-to-background ratios. Tumor uptake of 18F-OC was greater than that of 18F-FDG, and this was particularly evident in G2 NENs (median SUVmax, 45.6 vs 4.3; P < 0.015). Tumor uptake of 18F-OC or 18F-FDG was significantly correlated with tumor differentiation (P < 0.05). Dual tracer PET/CT detected more lesions and also yielded information on the biological status of tumors. Conclusions The tracer 18F-OC exhibited favorable safety and dosimetry profiles. 18F-OC provided superior imaging of well-differentiated NENs and significantly higher tumor-to-background ratio compared with 18F-FDG. Combining 18F-FDG with 18F-OC PET/CT has the potential to improve NEN staging and management of patient treatment.

[1]  B. Perez-Ordonez,et al.  Neuroendocrine Carcinomas of the Larynx and Head and Neck: Challenges in Classification and Grading , 2018, Head and Neck Pathology.

[2]  D. Metz,et al.  Appropriate Use Criteria for Somatostatin Receptor PET Imaging in Neuroendocrine Tumors , 2018, The Journal of Nuclear Medicine.

[3]  E. Scarpi,et al.  Investigation of receptor radionuclide therapy with 177Lu-DOTATATE in patients with GEP-NEN and a high Ki-67 proliferation index , 2018, European Journal of Nuclear Medicine and Molecular Imaging.

[4]  Shouhao Zhou,et al.  Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States , 2017, JAMA oncology.

[5]  W. Oyen,et al.  Guideline for PET/CT imaging of neuroendocrine neoplasms with 68Ga-DOTA-conjugated somatostatin receptor targeting peptides and 18F–DOPA , 2017, European Journal of Nuclear Medicine and Molecular Imaging.

[6]  J. Mortensen,et al.  Head-to-Head Comparison of 64Cu-DOTATATE and 68Ga-DOTATOC PET/CT: A Prospective Study of 59 Patients with Neuroendocrine Tumors , 2017, The Journal of Nuclear Medicine.

[7]  Edward Hsiao,et al.  Dual Somatostatin Receptor/FDG PET/CT Imaging in Metastatic Neuroendocrine Tumours: Proposal for a Novel Grading Scheme with Prognostic Significance , 2017, Theranostics.

[8]  S. Michopoulou,et al.  Comparison of the Impact of 68Ga-DOTATATE and 18F-FDG PET/CT on Clinical Management in Patients with Neuroendocrine Tumors , 2017, The Journal of Nuclear Medicine.

[9]  O. Prante,et al.  Radiosynthesis and Preclinical Evaluation of 18F-Fluoroglycosylated Octreotate for Somatostatin Receptor Imaging. , 2016, Bioconjugate chemistry.

[10]  P. Herscovitch,et al.  Prospective Study of 68Ga-DOTATATE Positron Emission Tomography/Computed Tomography for Detecting Gastro-Entero-Pancreatic Neuroendocrine Tumors and Unknown Primary Sites. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  S. Dubash Clinical translation of a ‘click’ labeled 18F-octreotate radioligand for imaging neuroendocrine tumors. , 2016 .

[12]  M. Andersson Erratum to: Effective dose to adult patients from 338 radiopharmaceuticals estimated using ICRP biokinetic data, ICRP/ICRU computational reference phantoms and ICRP 2007 tissue weighting factors , 2015, EJNMMI Physics.

[13]  J. Soucy,et al.  In Vivo Evaluation of 18F-SiFAlin–Modified TATE: A Potential Challenge for 68Ga-DOTATATE, the Clinical Gold Standard for Somatostatin Receptor Imaging with PET , 2015, The Journal of Nuclear Medicine.

[14]  I. Adalet,et al.  Can Complementary 68Ga-DOTATATE and 18F-FDG PET/CT Establish the Missing Link Between Histopathology and Therapeutic Approach in Gastroenteropancreatic Neuroendocrine Tumors? , 2014, The Journal of Nuclear Medicine.

[15]  F. Bénard,et al.  Preclinical Evaluation of a High-Affinity 18F-Trifluoroborate Octreotate Derivative for Somatostatin Receptor Imaging , 2014, The Journal of Nuclear Medicine.

[16]  I. Adalet,et al.  Establish the Missing Link Between Histopathology and Therapeutic Approach in Gastroenteropancreatic Neuroendocrine Tumors , 2014 .

[17]  P. Ell,et al.  Comparison of 68Ga-DOTANOC and 68Ga-DOTATATE PET/CT Within Patients with Gastroenteropancreatic Neuroendocrine Tumors , 2013, The Journal of Nuclear Medicine.

[18]  W. Oyen,et al.  Optimized labeling of NOTA-conjugated octreotide with F-18 , 2011, Tumor Biology.

[19]  S. Luthra,et al.  Targeting Somatostatin Receptors: Preclinical Evaluation of Novel 18F-Fluoroethyltriazole-Tyr3-Octreotate Analogs for PET , 2011, The Journal of Nuclear Medicine.

[20]  M. Schwaiger,et al.  Focal uptake of 68Ga-DOTATOC in the pancreas: pathological or physiological correlate in patients with neuroendocrine tumours? , 2011, European Journal of Nuclear Medicine and Molecular Imaging.

[21]  C. Boy,et al.  68Ga-DOTATOC PET/CT and somatostatin receptor (sst1–sst5) expression in normal human tissue: correlation of sst2 mRNA and SUVmax , 2011, European Journal of Nuclear Medicine and Molecular Imaging.

[22]  H. Wagner,et al.  Fluorine-18 radiopharmaceuticals beyond [18F]FDG for use in oncology and neurosciences. , 2010, Nuclear medicine and biology.

[23]  W. Oyen,et al.  A Novel Facile Method of Labeling Octreotide with 18F-Fluorine , 2010, Journal of Nuclear Medicine.

[24]  V. Prasad,et al.  Biodistribution of the Ga-68 labeled somatostatin analogue DOTA-NOC in patients with neuroendocrine tumors: characterization of uptake in normal organs and tumor lesions. , 2010, The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of....

[25]  A. Barlier,et al.  18F-FDG Avidity of Pheochromocytomas and Paragangliomas: A New Molecular Imaging Signature? , 2009, Journal of Nuclear Medicine.

[26]  A. Groves,et al.  Functional imaging of neuroendocrine tumors with combined PET/CT using 68Ga‐DOTATATE (DOTA‐DPhe1,Tyr3‐octreotate) and 18F‐FDG , 2008, Cancer.

[27]  R. Valkema,et al.  Molecular imaging as in vivo molecular pathology for gastroenteropancreatic neuroendocrine tumors: implications for follow-up after therapy. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[28]  Horst Kessler,et al.  First 18F-Labeled Tracer Suitable for Routine Clinical Imaging of sst Receptor-Expressing Tumors Using Positron Emission Tomography , 2004, Clinical Cancer Research.

[29]  M. Schwaiger,et al.  First (18)F-labeled tracer suitable for routine clinical imaging of sst receptor-expressing tumors using positron emission tomography. , 2004, Clinical cancer research : an official journal of the American Association for Cancer Research.

[30]  M. Schwaiger,et al.  PET imaging of somatostatin receptors: design, synthesis and preclinical evaluation of a novel 18F-labelled, carbohydrated analogue of octreotide , 2002, European Journal of Nuclear Medicine and Molecular Imaging.

[31]  E. Krenning,et al.  Comparison of 111In-DOTA-Tyr3-octreotide and 111In-DTPA-octreotide in the same patients: biodistribution, kinetics, organ and tumor uptake. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.