Theranostics Nuclear Medicine in Prostate Cancer

Abstract

Theranostic Nuclear Medicine is based on the idea of combining the same molecule (or drug) with different radioisotopes for both diagnosis and treatment, a concept that emerged in the early 1940s with the use of radioactive iodine for thyroid diseases. Theranostic Nuclear Medicine has since expanded to diseases of higher incidence, such as prostate cancer, with several imaging methods used to assess the extent of the disease and the corresponding radiopharmaceuticals used for treatment. For example, by detecting osteoblastic metastases by bone scintigraphy, corresponding radiopharmaceuticals with therapeutic properties can be administered to eliminate or reduce pain associated with metastases and/or determine overall survival gain. The purpose of this review is to discuss the role of Theranostic Nuclear Medicine in prostate cancer, addressing the main diagnostic imaging studies with their corresponding treatments in the Theranostic model.

Keywords: 177Lu-PSMA; 18F-FDG; 18F-fluoride; PET/CT; PSMA; Ra-223; nuclear medicine.

Figure 1

The concept of Theranostics in nuclear medicine, highlighting the structure of prostate-specific membrane antigen (PSMA). The large extracellular catalytic domain of PSMA (green) features binding sites for radioisotopes used in prostate cancer diagnosis, such as fluoride-18 (¹⁸F) and gallium-68 (⁶⁸Ga), and for treatment such as lutetium-177 (¹⁷⁷Lu) and actinium-225 (²²⁵Ac). The extracellular domains of PSMA are represented in light blue, the cell membrane lipid bilayer in pink, and the transmembrane domain with its intracellular antibody-binding site, in dark blue. Design adapted from Maurer T et al. (2016) [4].

Figure 2

Example of conventional bone scintigraphy and SPECT/CT using the radiopharmaceutical ^99mTc-MDP for primary staging of a prostate cancer patient (Gleason score 8). (A). Whole-body conventional images demonstrate abnormal uptake in the 3rd, 4th, and 5th lumbar spines. The abnormal uptake was equivocal for metastases. Therefore, the patient underwent SPECT/CT images. The fused axial (B), coronal (C), and sagittal (D) images demonstrate diffuse uptake in the lumbar spine with increased activity in areas consistent with degenerative processes, clearly seen in the CT images in the axial (E), coronal (F), and sagittal (G) planes. Therefore, the patient had degenerative processes and no osteoblastic bone metastases in this study.

Figure 3

Example of PET/CT images using the radiopharmaceutical ¹⁸F-FDG of a prostate cancer patient. The PET/CT images allow the simultaneous evaluation of biochemical and biological processes of the whole body (through the PET component) and anatomy (through the CT component). The metabolic images of PET are fused with the anatomic images of the CT scan. The coronal images of the (A) PET, (B) CT, and fused (C) PET/CT images demonstrate normal uptake and no metastases in this study.

Figure 4

Example of conventional bone scintigraphy and SPECT/CT using the radiopharmaceutical ^99mTc-MDP of a 62-year-old prostate cancer patient (Gleason, 3 + 4; PSA equals 11.3 ng/dL) undergoing the evaluation for primary staging. (A) Whole-body conventional images demonstrate a focal area of abnormal uptake (arrow) in the 3rd lumbar spine. The abnormal uptake was equivocal for metastases. Therefore, the patient underwent SPECT/CT images. The axial images in the fused SPECT/CT (B) and corresponding CT (C) demonstrate increased activity in areas consistent with osteoblastic bone metastasis.

Figure 5

Example of PET/CT using the radiopharmaceutical ¹⁸F-fluoride of an 85-year-old prostate cancer patient. The patient underwent the study for restaging purposes (Gleason, 4 +3; post-prostatectomy and radiotherapy) due to biochemical recurrence (PSA = 323 ng/dL). (A). Whole-body MIP (Maximum Intensity Projection) image demonstrates a focal area of abnormal uptake in the 1st lumbar vertebrae (arrowhead). The sagittal in the CT and fused images in the sagittal (B,C) and axial (D,E) images demonstrate increased activity in areas consistent with osteoblastic bone metastasis (yellow arrows).

Figure 6

Emission of alpha particles by Ra-223. These high-energy particles follow a very short distance after emission, destroying tumor cells without irradiating surrounding bone marrow and causing less toxicity. Cellular destruction causes irreversible events in the tumor cell by double-stranded DNA breakage, leading to apoptosis and necrosis.

Figure 7

PSMA PET/CT of a patient undergoing primary staging for prostate adenocarcinoma (Gleason 5 + 4 = 9) and PSA= 7.7 ng/mL. (A) MIP images show multiple focal regions of hyperexpression of PSMA receptors in the prostate (arrow), lymph node metastases (arrowheads), and bone (dotted arrows). The fused axial images demonstrate (B) the primary prostate cancer mass invading adjacent soft tissue and bladder; (C) a left internal iliac pelvic lymph node metastasis; (D) bone metastasis on the left sacral wing and S4/S5 invading soft tissue; (E) a vertebral metastasis. The proposed metabolic staging by molecular imaging (MI) with PSMA was mi T4N2M1c.

Figure 8

PSMA PET/CT of a patient undergoing restaging due to biochemical recurrence of prostate adenocarcinoma (Gleason 3 + 4; PSA = 0.8 ng/mL). (A) The MIP image shows multiple bilateral pelvic lymph node metastases with hyperexpression of PSMA receptors (arrowheads). The fused axial images demonstrate the metastases (green arrows) located in (B) a right internal iliac lymph node (0.6 cm; SUV = 11), (C) a right external iliac lymph node (0.5 cm; SUV = 3.4) and (D) a left internal iliac lymph node (0.3 cm; SUV = 4.2). There were no signs of local recurrence.

Figure 9

PSMA PET/CT demonstrated an unusual sight of metastasis infiltrating the penis of a patient with prostate adenocarcinoma.

Figure 10

Example of the Theranostic concept (molecular radiolabeling for diagnostic and therapy purposes). In this case, the same molecule (PSMA) was radiolabeled with two different isotopes (gallium-68 and lutetium-177). ⁶⁸Ga-PSMA was used for diagnosis of the extent of metastases from prostate cancer to plan therapy with ¹⁷⁷Lu-PSMA (A) ⁶⁸Ga-PSMA PET/CT image of a patient with extensive, wide-spread bone metastases from advanced prostate cancer with high PSMA uptake. Because of the avidity of the cancer cells to PSMA, the patient was programmed for personalized therapy with ¹⁷⁷Lu-PSMA. (B–F) images obtained 4 h after therapy showing the extent of bone metastasis with an initial PSA level of 85 ng/dL. In these subsequent cycles, the images obtained show excellent response to treatment. The patient presented with a progressive reduction of PSA levels, improvement of symptoms and performance status, and significant reduction of bone metastasis.