Somatostatin receptor PET in neuroendocrine tumours: 68Ga-DOTA0,Tyr3-octreotide versus 68Ga-DOTA0-lanreotide

Putzer, Daniel; Kroiss, Alexander; Waitz, Dietmar; Gabriel, Michael; Traub-Weidinger, Tatjana; Uprimny, Christian; Guggenberg, Elisabeth von; Decristoforo, Clemens; Warwitz, Boris; Widmann, Gerlig; Virgolini, Irene

doi:10.1007/s00259-012-2286-6

Cited by 45 publications

(21 citation statements)

References 24 publications

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“…The only PNET imaged by 68 Ga-DOTA-LAN, which was negative by 68 Ga-DOTA-TOC, exhibited an SUV max of 6.5 [41]. Pfeifer et al [42] reported a case of previously unknown PNET that was only confirmed 6 months later on CT in a patient with MEN I syndrome.…”

Section: Pancreatic Sstr-imaging—sensitivity Specificity and Suvmaxmentioning

confidence: 99%

Current knowledge on the sensitivity of the 68Ga-somatostatin receptor positron emission tomography and the SUVmax reference range for management of pancreatic neuroendocrine tumours

Virgolini

Gabriel

Kroiss

et al. 2016

Eur J Nucl Med Mol Imaging

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Physiologically increased pancreatic uptake at the head/uncinate process is observed in more than one-third of patients after injection of one of the three 68Ga-labelled octreotide-based peptides used for somatostatin (sst) receptor (r) imaging. There are minor differences between these 68Ga-sstr-binding peptides in the imaging setting. On 68Ga-sstr-imaging the physiological uptake can be diffuse or focal and usually remains stable over time. Differences in the maximal standardised uptake values (SUVmax) reported for the normal pancreas as well as for pancreatic neuroendocrine tumour (PNET) lesions may be related to several factors, including (a) differences in the peptide binding affinities as well as differences in sstr subtype expression of pancreatic α- and β-cells, and heterogeneity / density of tumour cells, (b) differences in scanner resolution, image reconstruction techniques and acquisition protocols, (c) mostly retrospective study designs, (d) mixed patient populations, or (e) interference with medications such as treatment with long-acting sst analogues. The major limitation in most of the studies lies in the lack of histopathological confirmation of abnormal findings. There is a significant overlap between the calculated SUVmax-values for physiological pancreas and PNET-lesions of the head/uncinate process that do not favour the use of quantitative parameters in the clinical setting. Anecdotal long-term follow-up studies have even indicated that increased uptake in the head/uncinate process still can turn out to be malignant over years of follow up. SUVmax-data for the pancreatic body and tail are limited. Therefore, any visible focal tracer uptake in the pancreas must be considered as suspicious for malignancy irrespective of quantitative parameters. In general, sstr-PET/CT has significant implications for the management of NET patients leading to a change in treatment decision in about one-third of patients. Therefore, follow-up with 68Ga-sstr-PET/CT is mandatory in the clinical setting if uptake in the head/uncinate process is observed.

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Section: Pancreatic Sstr-imaging—sensitivity Specificity and Suvmaxmentioning

confidence: 99%

Current knowledge on the sensitivity of the 68Ga-somatostatin receptor positron emission tomography and the SUVmax reference range for management of pancreatic neuroendocrine tumours

Virgolini

Gabriel

Kroiss

et al. 2016

Eur J Nucl Med Mol Imaging

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“…The statistical relationship between the PET/CT parameters and the response rate is shown in Table 2. (10,11). PRRT with Y-90 or Lu-177 labeled somatostatin analogs is a promising method at that stage of disease.…”

Section: Treatment Responsementioning

confidence: 99%

The role of baseline Ga-68 DOTATATE positron emission tomography/computed tomography in the prediction of response to fixed-dose peptide receptor radionuclide therapy with Lu-177 DOTATATE*

et al. 2016

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Background/aim: To describe the role of baseline gallium (Ga)-68 DOTATATE positron emission tomography (PET)/computed tomography (CT) in the prediction of the response to peptide receptor radionuclide therapy (PRRT) using lutetium (Lu)-177 DOTATATE.Materials and methods: Analysis was made of baseline Ga-68 DOTATATE PET/CT images of 29 patients (17 females and 12 males; mean age: 50.7 ± 14.6 years) with metastatic neuroendocrine tumors who received PRRT with Lu-177 DOTATATE. Maximum standardized uptake values (SUVmax) of reference lesions and their ratios to physiological uptake organs were calculated. The relationship between these values and the radiological response was analyzed.Results: Partial response was observed in 8 (28%) patients, stable disease in 18 (62%) patients, and progressive disease in 3 (10%) patients. Mean SUVmax of reference lesions was calculated as 23.8 ± 20.5 (min-max: 5.1-87.3). There was no significant correlation between radiological responses and SUVmax of reference lesions and their ratios to other organs. Conclusion:Baseline Ga-68 DOTATATE PET/CT helps to show somatostatin receptor expression status and disease stage in patients who are candidates for PRRT. However, SUVs do not have a role in the prediction of treatment response.

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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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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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Somatostatin receptor PET in neuroendocrine tumours: 68Ga-DOTA0,Tyr3-octreotide versus 68Ga-DOTA0-lanreotide

Cited by 45 publications

References 24 publications

Current knowledge on the sensitivity of the 68Ga-somatostatin receptor positron emission tomography and the SUVmax reference range for management of pancreatic neuroendocrine tumours

Current knowledge on the sensitivity of the 68Ga-somatostatin receptor positron emission tomography and the SUVmax reference range for management of pancreatic neuroendocrine tumours

The role of baseline Ga-68 DOTATATE positron emission tomography/computed tomography in the prediction of response to fixed-dose peptide receptor radionuclide therapy with Lu-177 DOTATATE*

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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Somatostatin receptor PET in neuroendocrine tumours: 68Ga-DOTA0,Tyr3-octreotide versus 68Ga-DOTA0-lanreotide

Cited by 45 publications

References 24 publications

Current knowledge on the sensitivity of the 68Ga-somatostatin receptor positron emission tomography and the SUVmax reference range for management of pancreatic neuroendocrine tumours

Current knowledge on the sensitivity of the 68Ga-somatostatin receptor positron emission tomography and the SUVmax reference range for management of pancreatic neuroendocrine tumours

The role of baseline Ga-68 DOTATATE positron emission tomography/computed tomography in the prediction of response to fixed-dose peptide receptor radionuclide therapy with Lu-177 DOTATATE*

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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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