Molecular Imaging of Prostate Cancer

Abstract

Prostate cancer is the most common noncutaneous malignancy among men in the Western world. The natural history and clinical course of prostate cancer are markedly diverse, ranging from small indolent intraprostatic lesions to highly aggressive disseminated disease. An understanding of this biologic heterogeneity is considered a necessary requisite in the quest for the adoption of precise and personalized management strategies. Molecular imaging offers the potential for noninvasive assessment of the biologic interactions underpinning prostate carcinogenesis. Currently, numerous molecular imaging probes are in clinical use or undergoing preclinical or clinical evaluation. These probes can be divided into those that image increased cell metabolism, those that target prostate cancer-specific membrane proteins and receptor molecules, and those that bind to the bone matrix adjacent to metastases to bone. The increased metabolism and vascular changes in prostate cancer cells can be evaluated with radiolabeled analogs of choline, acetate, glucose, amino acids, and nucleotides. The androgen receptor, prostate-specific membrane antigen, and gastrin-releasing peptide receptor (ie, bombesin) are overexpressed in prostate cancer and can be targeted by specific radiolabeled imaging probes. Because metastatic prostate cancer cells induce osteoblastic signaling pathways of adjacent bone tissue, bone-seeking radiotracers are sensitive tools for the detection of metastases to bone. Knowledge about the underlying biologic processes responsible for the phenotypes associated with the different stages of prostate cancer allows an appropriate choice of methods and helps avoid pitfalls.

©RSNA, 2016.

Figures

Figure 1.

Diagram of an overview of molecular imaging strategies currently applied for prostate cancer. Gray circles indicate the position of carbon 11 (11C) atoms. Curved arrows indicate free transmembranous diffusion. AATs = amino acid transporters, AR = androgen receptor, BA = bombesin analog, CT = choline transporter, 18F-FACBC = anti-fluorine 18 (18F)-1-amino-3-fluorocyclobutane-1-carboxylic acid, 18F-FDG = 18F-fluorodeoxyglucose, 18F-FDHT = 18F-16β-fluoro-5α-dihydrotestosterone, 18F-FLT = 18F-fluorothymidine, 18F-FMAU = 18F-fluoro-methyl-arabinofuranosyl-uracil, GLUT = glucose transporter, GRP-R = gastrin-releasing peptide receptor, hENT = human equilibrative nucleoside transporter, MCT = monocarboxylate transporter, PSMA = prostate-specific membrane antigen, SMI = small molecule inhibitor, TK = thymidine kinase, Y = antibody.

Figure 2.

Dual-modality 18F-choline PET and computed tomographic (CT) combined imaging (hereafter, PET/CT) of a 70-year-old man with recurrence of increased PSA levels 14 years after radical prostatectomy. (a, b) Early (a) and late (b) coronal maximum intensity projection images show the normal biodistribution of 18F-choline in the salivary glands, liver, pancreas, spleen, kidneys, bone marrow, and bowel, with urinary excretion depicted on b. In a, tracer accumulation is depicted in the left-sided paraaortic lymph nodes (arrows) and in one left-sided inguinal lymph node (arrowhead). In b, increased tracer uptake is depicted in the paraaortic nodes (arrows), a finding that is suspicious for metastasis; and after the same interval, the inguinal lymph node (arrowhead) shows decreased tracer uptake, which indicates that this lymph node is reactive. (c–f) Corresponding axial CT images (c, e) and fused late-phase PET/CT images (d, f) (c and d obtained at a lower level than e and f) show pathologic 18F-choline uptake in the left-sided paraaortic lymph nodes (arrow).

Figure 3.

18F-Choline PET/CT and MR imaging of a 66-year-old man with newly diagnosed prostate cancer and a PSA level of 30 ng/mL. (a) Early coronal maximum intensity projection image from 18F-choline PET shows unspecific focal 18F-choline uptake (arrow) in the left part of the prostate. (b) Axial T2-weighted MR image shows a hypointense lesion (arrow) in the left prostatic peripheral zone consistent with prostate cancer, a finding that was confirmed by the results of histopathologic examination. (c) Manually fused image combining axial PET image and axial MR image of the prostate depicts the 18F-choline activity (arrow) in the left peripheral zone.

Figure 4.

18F-Choline PET/CT and MR imaging of a 72-year-old man with newly diagnosed prostate cancer (Gleason score, 5 + 5 = 10). (a) Late coronal maximum intensity projection image from 18F-choline PET/CT shows focal tracer uptake in multiple bone lesions (arrows). (b) Axial fused PET/CT image of the pelvis depicts intense focal tracer uptake (arrows) in the left acetabulum, which helps confirm the findings in a. (c) Axial CT image shows minimal sclerotic changes (arrows) in the left acetabulum. (d) Corresponding axial T1-weighted MR image shows minimal hypointense changes (arrows) in the left acetabulum.

Figure 5.

18F-Choline PET/CT of a 70-year-old man with recurrence of an increased PSA level (1.9 ng/mL) 6 months after radical prostatectomy. (a) Early coronal maximum intensity projection shows focal tracer uptake in multiple lymph nodes (arrows). (b–d) Axial fused PET/CT images obtained at increasingly higher levels in the pelvis show the absence of focal tracer uptake in the prostate bed in b but also show intense focal activity in three pelvic lymph nodes (arrows in c, d).

Figure 6.

11C-Acetate PET/CT and gallium 68 (68Ga)–RM2 (bombesin analog) PET/CT of a 64-year-old man with newly diagnosed prostate cancer found at biopsy (Gleason score, 4 + 4 = 8; PSA level, 30 ng/mL), who was referred for cancer staging. (a, b)11C-Acetate PET/CT image (a) and 68Ga-RM2 (bombesin analog) PET/CT image (b) show a suspicious lesion (arrow in a, b) in the right prostatic peripheral zone. Note the physiologic uptake of 11C-acetate in the skeletal muscle on a. (c) Photograph of a macrosection obtained at robotic prostatectomy helps verify the presence of prostate cancer with invasion of the prostatic capsule (arrow). (Images courtesy of Heikki Minn, MD, Turku PET Centre, Turku, Finland.)

Figure 7.

FACBC PET/MR imaging of a 65-year-old man with newly diagnosed prostate cancer found at biopsy (Gleason score, 4 + 4 = 8; PSA level, 3.6 ng/mL), who was referred for cancer staging. (a) T2-weighted MR image of the pelvis shows an 8-mm external iliac lymph node (arrow). (b) Axial fused FACBC PET/MR image obtained with a fully integrated PET/MR system shows intense tracer uptake in the lymph node (arrow). The findings at histopathologic examination helped confirm lymph node metastases. (Images courtesy of Brage Krüger-Stokke, MD, NTNU-MR Cancer Group and St. Olavs Hospital, Trondheim, Norway.)

Figure 8.

FDHT PET/CT of a 64-year-old man with metastatic castration-resistant prostate cancer. (a, b) Images obtained at baseline examination: Coronal maximum intensity projection image obtained at FDHT PET (a) and sagittal fused FDHT PET/CT image (b) show diffuse osseous metastases. (c, d) Images obtained 6 weeks after treatment with cabozantinib (Cometriq; Exelixis, South San Francisco, Calif): Corresponding coronal maximum intensity projection image obtained at FDHT PET (c) and sagittal fused FDHT PET/CT image (d) show almost completely resolved uptake in the metastases to bone. FDHT is bound to sex hormone–binding globulin, which explains the considerable blood pool activity (red arrow in c). Note also the hepatobiliary excretion of the tracer into the bile ducts (green arrow in c) and the gallbladder (★ in c). The tracer is also excreted by way of the kidneys (yellow arrows in c) into the urinary bladder (arrowhead in c).

Figure 9.

Diagram of a PSMA molecule. The molecule is composed of a short intracellular domain (ID), a hydrophobic transmembranous domain (TD), and a large extracellular domain (ED). The latter consists of a large enzymatic portion and three smaller domains (*), the functions of which are not known. PSMA-directed imaging tracers can be divided into those targeting the ID and those that bind to the ED or inhibit its enzymatic domain. The ID contains a motif that is responsible for the internalization of the molecule into the endosomal recycling system of the cell.

Figure 10.

FDG PET and 89Zr-J591 imaging of a 55-year-old man with a mildly increasing PSA level of 1.1 ng/mL after radical prostatectomy. Coronal maximum intensity projection images obtained 60 minutes after intravenous injection of FDG(a) and 7 days after the injection of 89Zr-J591 (b) show physiologic tracer distribution for each tracer. No areas of abnormal tracer accumulation were depicted.

Figure 11.

FDG PET/CT, FDHT PET/CT, 89Zr-J591 PET/CT, and MR imaging of a 47-year-old man undergoing follow-up 2 years after prostatectomy and radiation therapy for prostate cancer (Gleason score, 4 + 5 = 9). Axial fused FDG PET/CT image (a), axial fused FDHT PET/CT image (b), axial fused 89Zr-J591 PET/CT image (c), and axial T1-weighted MR image (d) of the pelvis show a right superior pubic ramus metastasis extending into the acetabulum (arrow). Tracer uptake was depicted with all three PET tracers.

Figure 12.

FDG PET and 89Zr-J591 PET/CT of a 73-year-old man with metastatic castration-resistant prostate cancer. (a) Coronal maximum intensity projection image from FDG PET shows a few metastases to bone. (b–f) Coronal maximum intensity projection image from 89Zr-J591 PET (b) and axial fused 89Zr-J591 PET/CT images (c–f) depict many more metastases to bone.