ACP3 Theranostics in Prostate Cancer
4 affiliations
- 1School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430205, China
- 2CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
- 3Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China
- 4School of Future Medicine, Beijing University of Chinese Medicine, Beijing 100190, China
Abstract
Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) and radioligand therapy have established a major clinical paradigm for prostate cancer theranostics. Their performance is influenced by interpatient and interlesional heterogeneity, treatment-related changes in PSMA expression, and physiological ligand uptake in organs such as the salivary glands and kidneys, creating a rationale for complementary targets with different lesion coverage and normal-tissue distribution. ACP3 (acid phosphatase 3; historical symbol ACPP) encodes prostatic acid phosphatase (PAP), which is also termed prostate-specific acid phosphatase (PSAP) in older pathology literature. PAP has served as a serum biomarker, an immunohistochemical marker of prostatic origin, and an immunotherapeutic antigen. DNA-encoded library screening identified the high-affinity PAP ligand OncoACP3, and the resulting [177Lu]Lu-OncoACP3-DOTAGA radioligand and OncoACP3-GlyPro-MMAE small-molecule drug conjugate achieved target-dependent payload delivery and antitumor activity in preclinical models. First-in-human PET and subsequent pharmacokinetic and diagnostic dosimetry studies of [68Ga]Ga-OncoACP3-DOTA demonstrated visualization of localized and metastatic prostate cancer lesions and a normal-organ distribution distinct from that of PSMA-targeted ligands. This narrative review synthesizes the molecular characteristics and biological functions of PAP, historical clinical applications, and modern ACP3-targeted imaging and therapeutic platforms. Existing studies now provide a biological foundation, preclinical proof of targeted payload delivery, and early human imaging, pharmacokinetic, and diagnostic-dosimetry evidence. Prospective development should next define the ligand-accessible PAP pool, imaging-positivity criteria, therapeutic dosimetry, and the patient groups in whom ACP3 adds value to the PSMA theranostic framework.
Related
- Case Report: Prostatic infarction mimicking prostate cancer in a patient with markedly elevated prostate-specific antigen
- Prostate-specific antigen (PSA) test for prostate cancer screening
- Cancer‐Related Fever in Metastatic Prostate Cancer: A Case Report
- Cohort profile: the Prostate-Specific Antigen Cohort (PSA Cohort) and the Prostate Cancer Risk Cohort (ProCaRis Cohort) - cohorts based on Danish health data
- Pan-Cancer Analysis Identifies LUC7L2 as a Prognostic Biomarker and Potential Functional Regulator of Prostate Cancer Progression
BibTeX
@article{luo2026acp3,
title = {{ACP3 Theranostics in Prostate Cancer}},
author = {Zhilin Luo and Danlei Chen and Tianyi Ma and Pingping Zeng and Xuejie Li and Haoyuan Shi and Zhiyuan Hu},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18213511},
url = {https://www.mdpi.com/2072-6694/18/21/3511},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - ACP3 Theranostics in Prostate Cancer
AU - Zhilin Luo
AU - Danlei Chen
AU - Tianyi Ma
AU - Pingping Zeng
AU - Xuejie Li
AU - Haoyuan Shi
AU - Zhiyuan Hu
PY - 2026
DA - 2026/10/31
JO - Cancers
DO - 10.3390/cancers18213511
UR - https://www.mdpi.com/2072-6694/18/21/3511
AB - Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) and radioligand therapy have established a major clinical paradigm for prostate cancer theranostics. Their performance is influenced by interpatient and interlesional heterogeneity, treatment-related changes in PSMA expression, and physiological ligand uptake in organs such as the salivary glands and kidneys, creating a rationale for complementary targets with different lesion coverage and normal-tissue distribution. ACP3 (acid phosphatase 3; historical symbol ACPP) encodes prostatic acid phosphatase (PAP), which is also termed prostate-specific acid phosphatase (PSAP) in older pathology literature. PAP has served as a serum biomarker, an immunohistochemical marker of prostatic origin, and an immunotherapeutic antigen. DNA-encoded library screening identified the high-affinity PAP ligand OncoACP3, and the resulting [177Lu]Lu-OncoACP3-DOTAGA radioligand and OncoACP3-GlyPro-MMAE small-molecule drug conjugate achieved target-dependent payload delivery and antitumor activity in preclinical models. First-in-human PET and subsequent pharmacokinetic and diagnostic dosimetry studies of [68Ga]Ga-OncoACP3-DOTA demonstrated visualization of localized and metastatic prostate cancer lesions and a normal-organ distribution distinct from that of PSMA-targeted ligands. This narrative review synthesizes the molecular characteristics and biological functions of PAP, historical clinical applications, and modern ACP3-targeted imaging and therapeutic platforms. Existing studies now provide a biological foundation, preclinical proof of targeted payload delivery, and early human imaging, pharmacokinetic, and diagnostic-dosimetry evidence. Prospective development should next define the ligand-accessible PAP pool, imaging-positivity criteria, therapeutic dosimetry, and the patient groups in whom ACP3 adds value to the PSMA theranostic framework.
SN - 2072-6694
ER -