68Ga-DOTA-TOC uptake in neuroendocrine tumour and healthy tissue: differentiation of physiological uptake and pathological processes in PET/CT

Kroiss, Alexander; Putzer, Daniel; Decristoforo, Clemens; Uprimny, Christian; Warwitz, Boris; Nilica, Bernhard; Gabriel, Michael; Kendler, Dorota; Waitz, Dietmar; Widmann, Gerlig; Virgolini, Irene

doi:10.1007/s00259-012-2309-3

Cited by 93 publications

(54 citation statements)

References 22 publications

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“…This is to be expected because 18 F-FET-bAG-TOCA had both renal and biliary elimination, whereas 68 Ga-based ligands have predominantly renal elimination (21)(22)(23). In our cohort of patients with liver metastases, the tumor-to-background ratio for 18 F-FET-bAG-TOCA in the liver (4.23 6 2.69) was broadly similar to that reported for 68 Ga-DOTANOC (3.4 6 2.3), 68 Ga-DOTATOC (2.8 6 1.6), and 68 Ga-DOTATATE (2.0; interquartile range, 1.4-2.7) (24)(25)(26).…”

Section: Discussionsupporting

confidence: 57%

Clinical Translation of a Click-Labeled ¹⁸F-Octreotate Radioligand for Imaging Neuroendocrine Tumors

et al. 2016

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We conducted the first-in-human study of 18 F-fluoroethyl triazole [Tyr 3 ] octreotate ( 18 F-FET-βAG-TOCA) in patients with neuroendocrine tumors (NETs) to evaluate biodistribution, dosimetry, and safety. Despite advances in clinical imaging, detection and quantification of NET activity remains a challenge, with no universally accepted imaging standard. Methods: Nine patients were enrolled. Eight patients had sporadic NETs, and 1 had multiple endocrine neoplasia type 1 syndrome. Patients received 137-163 MBq (mean ± SD, 155.7 ± 8 MBq) of 18 F-FET-βAG-TOCA. Safety data were obtained during and 24 h after radioligand administration. Patients underwent detailed wholebody PET/CT multibed scanning over 4 h with sampling of venous bloods for radioactivity and radioactive metabolite quantification. Regions of interest were defined to derive individual and mean organ residence times; effective dose was calculated with OLINDA 1.1. Results: All patients tolerated 18 F-FET-βAG-TOCA with no adverse events. Over 60% parent radioligand was present in plasma at 60 min. High tumor (primary and metastases)-to-background contrast images were observed. Physiologic distribution was seen in the pituitary, salivary glands, thyroid, and spleen, with low background distribution in the liver, an organ in which metastases commonly occur. The organs receiving highest absorbed dose were the gallbladder, spleen, stomach, liver, kidneys, and bladder. The calculated effective dose over all subjects (mean ± SD) was 0.029 ± 0.004 mSv/MBq. Conclusion: The favorable safety, imaging, and dosimetric profile makes 18 F-FET-βAG-TOCA a promising candidate radioligand for staging and management of NETs. Clinical studies in an expanded cohort are ongoing to clinically qualify this agent.

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Section: Discussionsupporting

confidence: 57%

Clinical Translation of a Click-Labeled ¹⁸F-Octreotate Radioligand for Imaging Neuroendocrine Tumors

et al. 2016

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“…This represents a potential source of misinterpretation, since the pancreas and the duodenum are frequent sites of NENs. There have been attempts at defining an SUV max threshold to distinguish benign from malignant pancreatic uptake of DOTA-SSA peptides (34,35). However, given the large overlap between benign/physiologic and malignant uptake and the large interscanner measurement variance, mere uptake should not be used to diagnose pancreatic NENs without the demonstration of a clear lesion on the companion CT image or at correlative diagnostic cross-sectional imaging (36).…”

Section: Discussionmentioning

confidence: 99%

Current Concepts in ⁶⁸Ga-DOTATATE Imaging of Neuroendocrine Neoplasms: Interpretation, Biodistribution, Dosimetry, and Molecular Strategies

et al. 2017

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CME Credit: SNMMI is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing education for physicians. SNMMI designates each JNM continuing education article for a maximum of 2.0 AMA PRA category 1 credits. Physicians should claim only credit commensurate with the extent of their participation in the activity. For CE credit, SAM, and other credit types, participants can access this activity through the SNMMI website (http://www.snmmilearningcenter.org) through November 2020.68 Ga-DOTATATE PET/CT provides information on the location of somatostatin receptor-expressing tumors. Integrating this imaging data effectively in patient care requires the clinical history; the histopathology and biomarker information; and the grade, stage, and prior imaging results. Previous therapies and technical aspects of the study should be considered, given their ability to alter the interpretation of the images. This includes physiologic biodistribution of the radiotracer, as well as conditions that engender false-positive results. This article provides a guide to the performance and interpretation of 68 Ga-DOTATATE PET/CT and describes its role in the diagnostic algorithm of neuroendocrine neoplasms and its overall utility in their management.

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“…Clinical implementation of 68 Ga-labeled somatostatin analogs (e.g., 68 Ga-DOTATATE, 68 Ga-DOTATOC) for imaging of neuroendocrine tumors has raised attention because of the excellent imaging quality that can be achieved and the on-site availability of 68 Ga (half-life [T 1/2 ] 5 68 min, average b 1 energy [Eb 1 av ] 5 830 keV, intensity 5 89%) by the 68 Ge/ 68 Ga generator (2)(3)(4)(5)(6). Somatostatin receptor-targeted PET is currently used for dosimetry before application of 177 Lu-based radionuclide therapy (7).…”

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confidence: 99%

Promises of Cyclotron-Produced ⁴⁴Sc as a Diagnostic Match for Trivalent β⁻-Emitters: In Vitro and In Vivo Study of a ⁴⁴Sc-DOTA-Folate Conjugate

et al. 2013

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In recent years, implementation of 68 Ga-radiometalated peptides for PET imaging of cancer has attracted the attention of clinicians. Herein, we propose the use of 44 Sc (half-life 5 3.97 h, average b 1 energy [Eb 1 av ] 5 632 keV) as a valuable alternative to 68 Ga (half-life 5 68 min, Eb 1 av 5 830 keV) for imaging and dosimetry before 177 Lu-based radionuclide therapy. The aim of the study was the preclinical evaluation of a folate conjugate labeled with cyclotronproduced 44 Sc and its in vitro and in vivo comparison with the 177 Lulabeled pendant. Methods: 44 Sc was produced via the 44 Ca(p,n) 44 Sc nuclear reaction at a cyclotron (17.6 6 1.8 MeV, 50 mA, 30 min) using an enriched 44 Ca target (10 mg 44 CaCO 3 , 97.00%). Separation from the target material was performed by a semiautomated process using extraction chromatography and cation exchange chromatography. Radiolabeling of a DOTA-folate conjugate (cm09) was performed at 95°C within 10 min. The stability of 44 Sc-cm09 was tested in human plasma. 44 Sc-cm09 was investigated in vitro using folate receptor-positive KB tumor cells and in vivo by PET/CT imaging of tumor-bearing mice Results: Under the given irradiation conditions, 44 Sc was obtained in a maximum yield of 350 MBq at high radionuclide purity (.99%). Semiautomated isolation of 44 Sc from 44 Ca targets allowed formulation of up to 300 MBq of 44 Sc in a volume of 200-400 mL of ammonium acetate/HCl solution (1 M, pH 3.5-4.0) within 10 min. Radiolabeling of cm09 was achieved with a radiochemical yield of greater than 96% at a specific activity of 5.2 MBq/nmol. In vitro, 44 Sc-cm09 was stable in human plasma over the whole time of investigation and showed folate receptor-specific binding to KB tumor cells. PET/CT images of mice injected with 44 Sc-cm09 allowed excellent visualization of tumor xenografts. Comparison of cm09 labeled with 44 Sc and 177 Lu revealed almost identical pharmacokinetics. Conclusion: This study presents a highyield production and efficient separation method of 44 Sc at a quality suitable for radiolabeling of DOTA-functionalized biomolecules. An in vivo proof-of-concept study using a DOTA-folate conjugate demonstrated the excellent features of 44 Sc for PET imaging. Thus, 44 Sc is a valid alternative to 68 Ga for imaging and dosimetry before 177 Luradionuclide tumor therapy. In the past decade, applications of radiometal-based PET have rapidly increased, particularly for oncologic imaging purposes (1). Clinical implementation of 68 Ga-labeled somatostatin analogs (e.g., 68 Ga-DOTATATE, 68 Ga-DOTATOC) for imaging of neuroendocrine tumors has raised attention because of the excellent imaging quality that can be achieved and the on-site availability of 68 Ga (half-life [T 1/2 ] 5 68 min, average b 1 energy [Eb 1 av ] 5 830 keV, intensity 5 89%) by the 68 Ge/ 68 Ga generator (2-6). Somatostatin receptor-targeted PET is currently used for dosimetry before application of 177 Lu-based radionuclide therapy (7). These facts have established the basis of a new era of PET applicat...

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68Ga-DOTA-TOC uptake in neuroendocrine tumour and healthy tissue: differentiation of physiological uptake and pathological processes in PET/CT

Cited by 93 publications

References 22 publications

Clinical Translation of a Click-Labeled ¹⁸F-Octreotate Radioligand for Imaging Neuroendocrine Tumors

Clinical Translation of a Click-Labeled ¹⁸F-Octreotate Radioligand for Imaging Neuroendocrine Tumors

Current Concepts in ⁶⁸Ga-DOTATATE Imaging of Neuroendocrine Neoplasms: Interpretation, Biodistribution, Dosimetry, and Molecular Strategies

Promises of Cyclotron-Produced ⁴⁴Sc as a Diagnostic Match for Trivalent β⁻-Emitters: In Vitro and In Vivo Study of a ⁴⁴Sc-DOTA-Folate Conjugate

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68Ga-DOTA-TOC uptake in neuroendocrine tumour and healthy tissue: differentiation of physiological uptake and pathological processes in PET/CT

Cited by 93 publications

References 22 publications

Clinical Translation of a Click-Labeled 18F-Octreotate Radioligand for Imaging Neuroendocrine Tumors

Clinical Translation of a Click-Labeled 18F-Octreotate Radioligand for Imaging Neuroendocrine Tumors

Current Concepts in 68Ga-DOTATATE Imaging of Neuroendocrine Neoplasms: Interpretation, Biodistribution, Dosimetry, and Molecular Strategies

Promises of Cyclotron-Produced 44Sc as a Diagnostic Match for Trivalent β−-Emitters: In Vitro and In Vivo Study of a 44Sc-DOTA-Folate Conjugate

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Clinical Translation of a Click-Labeled ¹⁸F-Octreotate Radioligand for Imaging Neuroendocrine Tumors

Clinical Translation of a Click-Labeled ¹⁸F-Octreotate Radioligand for Imaging Neuroendocrine Tumors

Current Concepts in ⁶⁸Ga-DOTATATE Imaging of Neuroendocrine Neoplasms: Interpretation, Biodistribution, Dosimetry, and Molecular Strategies

Promises of Cyclotron-Produced ⁴⁴Sc as a Diagnostic Match for Trivalent β⁻-Emitters: In Vitro and In Vivo Study of a ⁴⁴Sc-DOTA-Folate Conjugate