Determination of HEPES in 68Ga-labeled peptide solutions

Sasson, Revital; Vaknin, David; Bross, Avihai; Lavie, E.

doi:10.1007/s10967-010-0449-0

Cited by 15 publications

(13 citation statements)

References 9 publications

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“…Importantly, we always found high uptake of 68 Ga-DOTANOC in the pituitary. The minimal uptake of 68 Ga-DOTANOC in the pituitary in their study indicates either a quality problem with the radiotracer (36) or possible saturation of sst receptors, which may influence the performance of the tracer and explain the discordant results compared with our study.…”

Section: Discussioncontrasting

confidence: 57%

Comparison of ⁶⁸Ga-DOTANOC and ⁶⁸Ga-DOTATATE PET/CT Within Patients with Gastroenteropancreatic Neuroendocrine Tumors

et al. 2013

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Somatostatin receptor PET tracers such as [ 68 Ga-DOTA, 1-Nal 3 ]-octreotide ( 68 Ga-DOTANOC) and [ 68 Ga-DOTA,Tyr 3 ]-octreotate ( 68 Ga-DOTATATE) have shown promising results in patients with neuroendocrine tumors, with a higher lesion detection rate than is achieved with 18 F-fluorodihydroxyphenyl-Lalanine PET, somatostatin receptor SPECT, CT, or MR imaging. 68 Ga-DOTANOC has high affinity for somatostatin receptor subtypes 2, 3, and 5 (sst 2,3,5 ). It has a wider receptor binding profile than 68 Ga-DOTATATE, which is sst 2 -selective. The wider receptor binding profile might be advantageous for imaging because neuroendocrine tumors express different subtypes of somatostatin receptors. The goal of this study was to prospectively compare 68 Ga-DOTANOC and 68 Ga-DOTATATE PET/CT in the same patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and to evaluate the clinical impact of 68 Ga-DOTANOC PET/CT. Methods: Eighteen patients with biopsy-proven GEP-NETs were evaluated with 68 Ga-DOTANOC and 68 Ga-DOTATATE using a randomized crossover design. Labeling of DOTANOC and DOTATATE with 68 Ga was standardized using a fully automated synthesis device. PET/CT findings were compared with 3-phase CT scans and in some patients with MR imaging, 18 F-FDG PET/CT, and histology. Uptake in organs and tumor lesions was quantified and compared by calculation of maximum standardized uptake values (SUVmax) using volume computer-assisted reading. Results: Histology revealed low-grade GEP-NETs (G1) in 4 patients, intermediate grade (G2) in 7, and high grade (G3) in 7. 68 Ga-DOTANOC and 68 Ga-DOTATATE were false-negative in only 1 of 18 patients. In total, 248 lesions were confirmed by crosssectional and PET imaging. The lesion-based sensitivity of 68 Ga-DOTANOC PET was 93.5%, compared with 85.5% for 68 Ga-DOTATATE PET (P 5 0.005). The better performance of 68 Ga-DOTANOC PET is attributed mainly to the significantly higher detection rate of liver metastases rather than tumor differentiation grade. Multivariate analysis revealed significantly higher SUVmax in G1 tumors than in G3 tumors (P 5 0.009).This finding was less pronounced with 68 Ga-DOTANOC (P . 0.001). Altogether, 68 Ga-DOTANOC changed treatment in 3 of 18 patients (17%). Conclusion: The sst 2,3,5 -specific radiotracer 68 Ga-DOTANOC detected significantly more lesions than the sst 2 -specific radiotracer 68 Ga-DOTATATE in our patients with GEP-NETs. The clinical relevance of this finding has to be proven in larger studies.

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Section: Discussioncontrasting

confidence: 57%

Comparison of ⁶⁸Ga-DOTANOC and ⁶⁸Ga-DOTATATE PET/CT Within Patients with Gastroenteropancreatic Neuroendocrine Tumors

et al. 2013

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“…4 Chromatograms of HEPES in the range of 6-100 μg/mL with an isocratic system of NH 4 HCO 2 20 mM pH 9.5, UV 195 nm, from 0 to 4 min have an LOQ of 3.2 μg/mL. These results are in similar range with a previously described HPLC method where the LOQ was 10 μg/mL 3 (Sasson et al 2010). With this new HPLC method, it was found that the presence of various solvents did not affect the quantification of HEPES.…”

Section: Discussionsupporting

confidence: 53%

“…The most common buffers used in these labeling are sodium acetate, ammonium acetate and 2-[4-N-(2hydroxyethyl)-1-piperazinyl]-N′-ethanesulfonic acid (HEPES). Some 68 Ga radiolabelling reactions have shown to be more efficient and stable when performed with a HEPES buffer solution (Sasson et al 2010).…”

Section: Introductionmentioning

confidence: 99%

New sensitive method for HEPES quantification in 68Ga-radiopharmaceuticals

Antunes

Franssen

Zijlma

et al. 2020

EJNMMI radiopharm. chem.

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Background: The introduction of a GMP-certified 68 Ga-generator spurred the application of 68 Ga-radiopharmaceuticals. Several radiosynthesis of 68 Garadiopharmaceuticals are more efficient and robust when performed with 2-[4-(2hydroxyethyl)piperazin-1-yl] ethanesulfonic acid (HEPES) buffer, which is considered as an impurity in the quality control (QC) procedure. Thus, prior to clinical use, QC must be conducted to ensure that HEPES does not exceed the maximum dose of 200 μg/V Injected as described in European Pharmacopoeia (Ph Eur) for edotreotide. However, when applying the thin-layer chromatography (TLC) method described in the Ph Eur to quantify the HEPES amount present in the 68 Ga-octreotide or in the remaining 68 Ga-radiopharmaceuticals that were tested, no amount was detectable after 4 min of iodine incubation. Here we tested our modified TLC method and validate a new high-performance liquid chromatography (HPLC) method to quantify HEPES in 68 Ga-radiopharmaceuticals and compare it to the TLC-method described in Ph Eur. In addition, samples collected from various institutes were tested to evaluate whether the synthesis of different 68 Ga-radiopharmaceuticals or the use of different synthesis methods could affect the amounts of HEPES. Results: HEPES could not be detected by the TLC method described in the Ph Eur within 4 min incubation in an iodine-saturated chamber. As for our modified TLC method, only after 2 h, spots were only visible > 1 mg/mL. The HPLC method had a limit-of-quantification (LOQ) of 3 μg/mL and a limit-of-detection (LOD) of 1 μg/mL. From the three 68 Ga-radiopharmaceuticals tested, only in the [ 68 Ga]Ga-NODAGA-Exendin samples exceeding amounts of HEPES were found and its concentration in the [ 68 Ga]Ga-NODAGA-Exendin was significantly higher, when compared to [ 68 Ga]Ga-DOTATOC and [ 68 Ga]Ga-PSMA-11. Conclusion: The TLC method described in Ph Eur and our modified TLC method may not be sufficiently sensitive and thus unsuitable to use for QC release. The new HPLC method was sensitive, quantitative, reproducible and suitable for QC release. With this method, we were able to determine that some 68 Ga-radiopharmaceuticals may exceed the HEPES limit of 200 μg/ V Injected. This new analytical system would allow correcting for the maximum injected dose in order not to exceed this amount.

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“…This TLC assay was reported as neither reliable nor suitable and an improvement of this method would be highly advantageous [ 11 ]. As a result, a lot of effort has been made in the optimization and validation of an improved method for quantification of HEPES in radiopharmaceuticals by means of HPLC chromatography according to Kvaternik et al and Antunes et al [ 11 – 13 ].…”

Section: Introductionmentioning

confidence: 99%

Development and evaluation of a rapid analysis for HEPES determination in 68Ga-radiotracers

et al. 2018

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BackgroundHEPES is a favorable buffer for 68Ga-complexations in radiochemical laboratories. The drawback of this buffer is its prescribed limit of 200 μg per recommended application volume in the final formulation. Currently, a TLC test according to the European Pharmacopoeia (Ph. Eur.) has to be performed for quantification, but this analysis suffers from low reliability and reproducibility and is based on a subjective, semi-quantitative visual evaluation. In this study, the TLC method according to the Ph. Eur. and two literature-known HPLC assays for HEPES quantification were evaluated. Additionally, the development of an improved TLC method was performed.ResultsThe assay according to Antunes et al. provided a reasonable quantification of HEPES using HPLC. Additionally, a reliable and conclusive TLC method was developed, which facilitates quantitative analysis by means of a pixel-based evaluation. A comparison of those two methods with the Ph. Eur. TLC assay pinpoints the superiority of the HPLC as well as the new TLC assay. Furthermore, evaluation of HEPES contents using both TLC assays by 28 subjects supported the conclusion that the newly developed TLC method is clearly favorable.ConclusionThe TLC method according to the Ph. Eur. provides unsatisfactory results in terms of conclusiveness and reproducibility. In contrast, a reported HPLC assay showed valid results, with the drawback of high technical effort. An optimized alternative is provided by the improved TLC method described in this work that results in reliable outcomes and additionally offers quantitative analysis.

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Determination of HEPES in 68Ga-labeled peptide solutions

Cited by 15 publications

References 9 publications

Comparison of ⁶⁸Ga-DOTANOC and ⁶⁸Ga-DOTATATE PET/CT Within Patients with Gastroenteropancreatic Neuroendocrine Tumors

Comparison of ⁶⁸Ga-DOTANOC and ⁶⁸Ga-DOTATATE PET/CT Within Patients with Gastroenteropancreatic Neuroendocrine Tumors

New sensitive method for HEPES quantification in 68Ga-radiopharmaceuticals

Development and evaluation of a rapid analysis for HEPES determination in 68Ga-radiotracers

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Determination of HEPES in 68Ga-labeled peptide solutions

Cited by 15 publications

References 9 publications

Comparison of 68Ga-DOTANOC and 68Ga-DOTATATE PET/CT Within Patients with Gastroenteropancreatic Neuroendocrine Tumors

Comparison of 68Ga-DOTANOC and 68Ga-DOTATATE PET/CT Within Patients with Gastroenteropancreatic Neuroendocrine Tumors

New sensitive method for HEPES quantification in 68Ga-radiopharmaceuticals

Development and evaluation of a rapid analysis for HEPES determination in 68Ga-radiotracers

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Product

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Comparison of ⁶⁸Ga-DOTANOC and ⁶⁸Ga-DOTATATE PET/CT Within Patients with Gastroenteropancreatic Neuroendocrine Tumors

Comparison of ⁶⁸Ga-DOTANOC and ⁶⁸Ga-DOTATATE PET/CT Within Patients with Gastroenteropancreatic Neuroendocrine Tumors