Comparison of [(11)C]Choline ([(11)C]CHO) and [(18)F]Bombesin (BAY 86-4367) as Imaging Probes for Prostate Cancer in a PC-3 Prostate Cancer Xenograft Model.
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.
Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany. sarah.schwarzenboeck@med.uni-rostock.de.|Department of Nuclear Medicine, Rostock University Medical Centre, Gertrudenplatz 1, 18057, Rostock, Germany. sarah.schwarzenboeck@med.uni-rostock.de.
Sarah Marie
SM
Schwarzenböck
Department of Nuclear Medicine, Rostock University Medical Centre, Gertrudenplatz 1, 18057, Rostock, Germany.
Philipp
P
Schmeja
Department of Nuclear Medicine, Rostock University Medical Centre, Gertrudenplatz 1, 18057, Rostock, Germany.
Jens
J
Kurth
Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany.|Department of Nuclear Medicine, Ulm University, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
Michael
M
Souvatzoglou
Department of Urology, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany.
Roman
R
Nawroth
Department of Urology, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany.
Uwe
U
Treiber
Department of Biostatistics and Informatics, Rostock University Medical Centre, Ernst-Heydemann-Str. 8, 18057, Rostock, Germany.
Guenther
G
Kundt
Global Drug Discovery, Bayer Healthcare, Muellerstr. 178, 13353, Berlin, Germany.
Sandra
S
Berndt
Global Drug Discovery, Bayer Healthcare, Muellerstr. 178, 13353, Berlin, Germany.
Keith
K
Graham
Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany.
Reingard
R
Senekowitsch-Schmidtke
Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany.
Markus
M
Schwaiger
Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany.
Sibylle I
SI
Ziegler
Piramal Imaging, GmbH, Tegeler Strasse 6-7, 13353, Berlin, Germany.
Ludger
L
Dinkelborg
Institution of Pharmaceutical Radiochemistry, Technische Universität München, Walther-Meißner-Str. 3, 85748, Garching, Germany.
Hans-Jürgen
HJ
Wester
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.
Bernd Joachim
BJ
Krause
D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D002250:Carbon Radioisotopes; D045744:Cell Line, Tumor; D002794:Choline / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D051379:Mice; D015335:Molecular Probes / Q000737:chemistry*; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D011471:Prostatic Neoplasms / Q000097:blood / Q000000981:diagnostic imaging* / Q000473:pathology; D019275:Radiopharmaceuticals / Q000737:chemistry*; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays
C556307:BAY 86-4367; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D015335:Molecular Probes; D019275:Radiopharmaceuticals; D002794:Choline; D001839:Bombesin
Bombesin; Choline; Prostate cancer; Small animal PET/CT; Xenograft mouse model