The Application of Radiolabeled Targeted Molecular Probes for the Diagnosis and Treatment of Prostate Cancer

Abstract

Radiopharmaceuticals targeting prostate-specific membrane antigens (PSMA) are essential for the diagnosis, evaluation, and treatment of prostate cancer (PCa), particularly metastatic castration-resistant PCa, for which conventional treatment is ineffective. These molecular probes include [⁶⁸Ga]PSMA, [¹⁸F]PSMA, [Al¹⁸F]PSMA, [^99mTc]PSMA, and [⁸⁹Zr]PSMA, which are widely used for diagnosis, and [¹⁷⁷Lu]PSMA and [²²⁵Ac]PSMA, which are used for treatment. There are also new types of radiopharmaceuticals. Due to the differentiation and heterogeneity of tumor cells, a subtype of PCa with an extremely poor prognosis, referred to as neuroendocrine prostate cancer (NEPC), has emerged, and its diagnosis and treatment present great challenges. To improve the detection rate of NEPC and prolong patient survival, many researchers have investigated the use of relevant radiopharmaceuticals as targeted molecular probes for the detection and treatment of NEPC lesions, including DOTA-TOC and DOTA-TATE for somatostatin receptors, 4A06 for CUB domain-containing protein 1, and FDG. This review focused on the specific molecular targets and various radionuclides that have been developed for PCa in recent years, including those mentioned above and several others, and aimed to provide valuable up-to-date information and research ideas for future studies.

Keywords: Neuroendocrine prostate cancer; Prostate cancer; Prostate specific membrane antigen; Radionuclide imaging; Radionuclide treatment.

Fig. 1. Maximum intensity projections (MIPs), axial images of positron emission tomography (PET), and axial fusion images of PET-computed tomography (CT) using [⁶⁸Ga]Ga-PSMA-11 (A, B, C) and [¹⁸F]F-PSMA-1007 (D, E, F) in a 67-year-old male with Gleason 8 and PSA 4.9 ng/mL. The MIP image of [⁶⁸Ga]Ga-PSMA-11 (A) (arrow) shows significant uptake in the bladder and left ureter, while urinary excretion of [¹⁸F]F-PSMA-1007 (F) is virtually absent. Lesions in the left prostate lobe are visible on both scans (arrowheads in B, D). However, the second lesion in the right lobe is only visible under [¹⁸F]F-PSMA-1007 (arrow in D), and has been pathologically confirmed to be a malignant lesion. Reprinted with permission from Kuten et al. [39] (J Nucl Med 2020;61:527-532; https://doi.org/10.2967/jnumed.119.234187). PSMA = prostate-specific membrane antigen

Fig. 2. [⁶⁸Ga]Ga-PSMA-11 positron emission tomography-computed tomography (PET-CT) scans of a patient with prostate cancer before and after radionuclide therapy. A: [⁶⁸Ga]Ga-PSMA-11 PET-CT imaging before radionuclide therapy. B: Progression is observed after 2 cycles of treatment with beta-emitting [¹⁷⁷Lu]Lu-PSMA-617. Promising treatment results after two (C) and three (D) cycles of treatment with α-emitting [²²⁵Ac]Ac-PSMA-617. Reprinted with permission from Kratochwil et al. [68] (J Nucl Med 2016;57:1941-1944; https://doi.org/10.2967/jnumed.116.178673).

Fig. 3. Maximum intensity projection (MIP) of positron emission tomography (PET) and trans-axial fusion images of PET-computed tomography (CT) scans of a 53-year-old male with post-operative relapse of his prostate cancer. Al[¹⁸F]F-PSMA PET-CT shows no uptake in the recurrent lesions (A, D). [¹⁸F]FDG PET-CT shows multiple lesions with high uptake throughout the body (B, E). After six cycles of chemotherapy, [¹⁸F]FDG PET-CT demonstrates that multiple lesions are significantly reduced in size and radioactive uptake (C, F).