Molecular MR Imaging of Prostate Cancer

Abstract

This review summarizes recent developments regarding molecular imaging markers for magnetic resonance imaging (MRI) of prostate cancer (PCa). Currently, the clinical standard includes MR imaging using unspecific gadolinium-based contrast agents. Specific molecular probes for the diagnosis of PCa could improve the molecular characterization of the tumor in a non-invasive examination. Furthermore, molecular probes could enable targeted therapies to suppress tumor growth or reduce the tumor size.

Keywords: magnetic resonance imaging; molecular imaging; molecular marker; prostate cancer.

Figure 1

ProCA1.GRPR distribution and gastrin-releasing receptor (GRPR) expression in xenografted tumor tissue from Pu et al. 2015 (modified); (a,b) Immunofluorescence staining of ProCA1.GRPR targeting GRPR on (a) H441 and (b) PC3 tumors in xenograft mice. Blue: nucleus staining. Red: Staining GRPR on (a) H441 and (b) PC3 tumor. (c) Graphical representation of fluorescence intensity of ProCA1.GRPR staining in PC3 and H441 tumors. PC3 tumor shows a stronger expression as H441 tumors. (d) T1-weighted spin echo MR imaging of ProCA1.GRPR targeting GRPR in H441 (blue arrow) and PC3 (red arrow) in mice (xenograft). (e) T1-weighted spin echo MR imaging of non-targeted ProCA1 in H441 (blue arrow) and PC3 (red arrow) in mice (xenograft). Scale bar = 100 μm. Colorbars show the signal intensity (from high (red) to low (black)).

Figure 2

MR signal intensity versus time with c-myc-specific Gd³⁺ complex from Heckl et al. 2003 (modified); (A) (red) The signalintensity of the c-myc-Gd³⁺ comlex for HeLa cells after incubation, and (B) by lymphocytes. These are axial T1 weighted images of the cell pellets, in Minimum Essential Media (MEM), each consisting of 20 × 10⁶ cells/ lymphocytes. (C) The intensity after intravenous injection of AT-1 (Dunning R- 3327) rat with prostate adenocarcinoma by coronal T1-weighted MR images (TR: 600 ms/TE: 15 ms; scan time, 45 s). All experiments were performed using a 1.5 Tesla Siemens Magnetom.

Figure 3

Illustration of signal amplification of CREKA-dL-(Gd-DOTA)₄ from Wu et al. 2014 (modified); (A) T1-weighted axial 2D images of orthotopic prostate cancer mice model before and at different time points after injection of CREKA-dL-(Gd-DOTA)₄. (B) T1-weighted axial 2D images of orthotopic prostate cancer mice model before and at different time points after injection of KAREC-dL-(Gd-DOTA)₄. The animals were injected with 0.03 mmol-Gd/kg in nu/nu nude mice. (C) Signal amplification ratio in tumor tissue: The ratio of signal intensity after contrast agent administration to that before contrast agent administration, up to 30 min after contrast agent injection, * p < 0.05.

Figure 4

Molecular characterization of muJ591:MIRK from Bates et al. (2014); (A) a Scanning Electron Micrograph (SEM) image. (B) A superposition of the elements C, O, N and Fe (SEM mapping with Energy Dispersive X-ray (EDX)). Soild arrow shows the iron signal (MIRB nanoparticles) and the dashed arrow shows the antibody as organic matter signal. For Scanning Electron Micrograph (SEM) imaging, the sample must be completely dry. The result of this step is the formation of crystalline salts from the buffer (large white structures).

Figure 5

Fluorescence microscopic images of prostate specific tumor cells with muJ591:MIRB from Bates et al. (2014); The images show antibody staining. (A) Extracellular and subcellular area LNCaP cells. (B) DU145 cells as negative control. (C) Rhodamine-B fluorophore detection (red) on LNCaP cells. (D) DU145 cells as negative control for detection.

Figure 6

Immunohistological staining of AMACR from Shapovalova M. et al. 2018 (modified); Comparison between (A) a healthy prostate and (B) prostate cancer. Scale bars = 200 μm.