Comparison between 68Ga-bombesin (68Ga-BZH3) and the cRGD tetramer 68Ga-RGD4 studies in an experimental nude rat model with a neuroendocrine pancreatic tumor cell line | springermedicine.com

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Open Access 01-12-2011 | Original research

Comparison between ⁶⁸Ga-bombesin (⁶⁸Ga-BZH3) and the cRGD tetramer ⁶⁸Ga-RGD₄ studies in an experimental nude rat model with a neuroendocrine pancreatic tumor cell line

Authors: Caixia Cheng, Leyun Pan, Antonia Dimitrakopoulou-Strauss, Martin Schäfer, Carmen Wängler, Björn Wängler, Uwe Haberkorn, Ludwig G Strauss

Published in: EJNMMI Research | Issue 1/2011

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Abstract

Objectives

Receptor scintigraphy gains more interest for diagnosis and treatment of tumors, in particular for neuroendocrine tumors (NET). We used a pan-Bombesin analog, the peptide DOTA-PEG₂-[D-tyr⁶, β-Ala¹¹, Thi¹³, Nle¹⁴] BN(6-14) amide (BZH3). BZH3 binds to at least three receptor subtypes: the BB1 (Neuromedin B), BB2 (Gastrin-releasing peptide, GRP), and BB3. Imaging of ανβ3 integrin expression playing an important role in angiogenesis and metastasis was accomplished with a ⁶⁸Ga-RGD tetramer. The purpose of this study was to investigate the kinetics and to compare both tracers in an experimental NET cell line.

Methods

This study comprised nine nude rats inoculated with the pancreatic tumor cell line AR42J. Dynamic positron emission tomography (PET) scans using ⁶⁸Ga-BZH3 and ⁶⁸Ga-RGD tetramer were performed (⁶⁸Ga-RGD tetramer: n = 4, ⁶⁸Ga-BZH3: n = 5). Standardized uptake values (SUVs) were calculated, and a two-tissue compartmental learning-machine model (calculation of K 1 - k 4 vessel density (VB) and receptor binding potential (RBP)) as well as a non-compartmental model based on the fractal dimension was used for quantitative analysis of both tracers. Multivariate analysis was used to evaluate the kinetic data.

Results

The PET kinetic parameters showed significant differences when individual parameters were compared between groups. Significant differences were found in FD, VB, K 1, and RBP (p = 0.0275, 0.05, 0.05, and 0.0275 respectively). The 56- to 60-min SUV for ⁶⁸Ga-BZH3, with a range of 0.86 to 1.29 (median, 1.19) was higher than the corresponding value for the ⁶⁸Ga-RGD tetramer, with a range of 0.78 to 1.31 (median, 0.99). Furthermore, FD, VB, K 1, and RBP for ⁶⁸Ga-BZH3 were generally higher than the corresponding values for the ⁶⁸Ga-RGD tetramer, whereas k 3 was slightly higher for ⁶⁸Ga-RGD tetramer.

Conclusions

As a parameter that reflects receptor binding, the increase of K 1 for ⁶⁸Ga-BZH3 indicated higher expression of bombesin receptors than that of the ανβ3 integrin in neuroendocrine tumors. ⁶⁸Ga-BZH3 seems better suited for diagnosis of NETs owing to higher global tracer uptake.

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Title: Comparison between 68Ga-bombesin (68Ga-BZH3) and the cRGD tetramer 68Ga-RGD4 studies in an experimental nude rat model with a neuroendocrine pancreatic tumor cell line
Authors: Caixia Cheng
Leyun Pan
Antonia Dimitrakopoulou-Strauss
Martin Schäfer
Carmen Wängler
Björn Wängler
Uwe Haberkorn
Ludwig G Strauss
Publication date: 01-12-2011
Publisher: Springer Berlin Heidelberg
Published in: EJNMMI Research / Issue 1/2011
Electronic ISSN: 2191-219X
DOI: https://doi.org/10.1186/2191-219X-1-34

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