Carbon-11- and fluorine-18-labeled choline derivatives are commonly used in prostate cancer imaging in the clinical setting for staging and re-staging of prostate cancer. Due to a limited detection rate of established positron emission tomography (PET) tracers, there is a clinical need for innovative tumor-specific PET compounds addressing new imaging targets.
The aim of this study was to compare the properties of [(18)F]Bombesin (BAY 86-4367) as an innovative biomarker for prostate cancer imaging targeting the gastrin-releasing peptide receptor and [(11)C]Choline ([(11)C]CHO) in a human prostate tumor mouse xenograft model by small animal PET/X-ray computed tomography (CT).
We carried out a dual-tracer small animal PET/CT study comparing [(18)F]Bombesin and [(11)C]CHO. The androgen-independent human prostate tumor cell line PC-3 was implanted subcutaneously in the flanks of nu/nu NMRI mice (n = 10) (PET/CT measurements of two [(11)C]Choline mice could not be analyzed due to technical reasons). [(18)F]Bombesin and [(11)C]CHO PET/CT imaging was performed about 3-4 weeks after the implantation of PC-3 cells on two separate days. After the intravenous tail vein injection of 14 MBq [(18)F]Bombesin and 37 MBq [(11)C]CHO, respectively, a dynamic study over 60 min was acquired in list mode using an Inveon animal PET/CT scanner (Siemens Medical Solutions). The sequence of [(18)F]Bombesin and [(11)C]CHO was randomized. Image analysis was performed using summed images as well as dynamic data. To calculate static and dynamic tumor-to-muscle (T/M), tumor-to-blood (T/B), liver-to-blood (L/B), and kidney-to-blood (K/B) ratios, 4 × 4 × 4 mm(3) volumes of interest (VOIs) of tumor, muscle (thigh), liver, kidney, and blood derived from transversal slices were used.
The mean T/M ratio of [(18)F]Bombesin and [(11)C]CHO was 6. 54 ± 2. 49 and 1. 35 ± 0. 30, respectively. The mean T/B ratio was 1. 83 ± 0. 79 for [(18)F]Bombesin and 0. 55 ± 0. 10 for [(11)C]CHO. The T/M ratio as well as the T/B ratio for [(18)F]Bombesin were significantly higher compared to those for [(11)C]CHO (p < 0. 001, respectively). Kidney and liver uptake was statistically significantly lower for [(18)F]Bombesin (K/B 3. 41 ± 0. 81, L/B 1. 99 ± 0. 38) compared to [(11)C]CHO [K/B 7. 91 ± 1. 85 (p < 0. 001), L/B 6. 27 ± 1. 99 (p < 0. 001)]. The magnitudes of the time course of T/M and T/B ratios (T/M and T/Bdyn ratios) were statistically significantly different (showing a higher uptake of [(18)F]Bombesin compared to [(11)C]CHO); additionally, also the change of the T/M and T/B ratios over time was significantly different between both tracers in the dynamic analysis (p < 0. 001, respectively). Furthermore, there was a statistically significantly different change of the K/B and L/B ratios over time between the two tracers in the dynamic analysis (p = 0. 026 and p < 0. 001, respectively).
[(18)F]Bombesin (BAY 86-4367) visually and semi-quantitatively outperforms [(11)C]CHO in the PC-3 prostate cancer xenograft model. [(18)F]Bombesin tumor uptake was significantly higher compared to [(11)C]CHO. [(18)F]Bombesin showed better imaging properties compared to the clinically utilized [(11)C]CHO due to a higher tumor uptake as well as a lower liver and kidney uptake.
Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging. 2015 Oct 19 [Epub ahead of print]
Sarah Marie Schwarzenböck, Philipp Schmeja, Jens Kurth, Michael Souvatzoglou, Roman Nawroth, Uwe Treiber, Guenther Kundt, Sandra Berndt, Keith Graham, Reingard Senekowitsch-Schmidtke, Markus Schwaiger, Sibylle I Ziegler, Ludger Dinkelborg, Hans-Jürgen Wester, Bernd Joachim Krause
Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany. Department of Nuclear Medicine, Rostock University Medical Centre, Gertrudenplatz 1, 18057, Rostock, Germany. , Department of Nuclear Medicine, Rostock University Medical Centre, Gertrudenplatz 1, 18057, Rostock, Germany. , Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany. , Department of Urology, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany. , Department of Urology, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany. , Department of Biostatistics and Informatics, Rostock University Medical Centre, Ernst-Heydemann-Str. 8, 18057, Rostock, Germany. , Global Drug Discovery, Bayer Healthcare, Muellerstr. 178, 13353, Berlin, Germany. , Global Drug Discovery, Bayer Healthcare, Muellerstr. 178, 13353, Berlin, Germany. , Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany. , Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany. , Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany. , Piramal Imaging, GmbH, Tegeler Strasse 6-7, 13353, Berlin, Germany. , Institution of Pharmaceutical Radiochemistry, Technische Universität München, Walther-Meißner-Str. 3, 85748, Garching, Germany. , Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany.