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Preliminary clinical study of p-iodo benzoyl moiety-modified PSMA inhibitors and prospective comparison with 68Ga-PSMA-11
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Preliminary clinical study of p-iodo benzoyl moiety-modified PSMA inhibitors and prospective comparison with 68Ga-PSMA-11
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Journal Article
Preliminary clinical study of p-iodo benzoyl moiety-modified PSMA inhibitors and prospective comparison with 68Ga-PSMA-11
2025
Overview
Small-molecule inhibitors targeting prostate-specific membrane antigen (PSMA) have demonstrated promising results in the theranostics of prostate cancer (PCa). We designed and synthesized a novel small-molecule PSMA inhibitor, SC691. This study aimed to conduct a preliminary clinical prospective investigation of
68
Ga-SC691. Following predefined inclusion/exclusion criteria, this study enrolled 7 healthy volunteers and 12 patients with PCa. Patients underwent
68
Ga-SC691 and
68
Ga-PSMA-11 PET/CT imaging within one week. PET/CT data were analyzed using a uWS-MI workstation.
68
Ga-SC691 demonstrated favorable safety profiles in all participants.
68
Ga-SC691 was primarily excreted via the urinary system, exhibiting a biodistribution similar to that of
68
Ga-PSMA-11. Compared to
68
Ga-PSMA-11,
68
Ga-SC691 showed lower non-specific organs uptake, particularly in the liver: 2.5 ± 0.7 vs. 4.1 ± 1.6 (
P
= 0.002). Furthermore,
68
Ga-SC691 and
68
Ga-PSMA-11 detected the same number and location of PSMA-positive lesions in PCa primary tumors, bone metastases, and lymph nodes metastases. Notably,
68
Ga-SC691 demonstrated higher tumor-to-non-tumor ratios (T/NT) (
P
< 0.05). In conclusions, as a novel small-molecule PSMA inhibitor, SC691 exhibits a favorable safety profile, biodistribution, and diagnostic performance, suggesting its potential as a valuable agent for PCa imaging and therapy. The lower non-specific organ uptake further supports its promise for theranostic applications.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 692/4017
/ 692/4025
/ 692/4028
/ Aged
/ Antigens, Surface - metabolism
/ Cancer
/ Edetic Acid - analogs & derivatives
/ Glutamate Carboxypeptidase II - antagonists & inhibitors
/ Humanities and Social Sciences
/ Humans
/ Male
/ PET/CT
/ Positron Emission Tomography Computed Tomography - methods
/ Prostate
/ Prostate-Specific membrane antigen (PSMA)
/ Prostatic Neoplasms - diagnostic imaging
/ Prostatic Neoplasms - drug therapy
/ Prostatic Neoplasms - metabolism
/ Prostatic Neoplasms - pathology
/ Radiopharmaceuticals - pharmacokinetics
/ Science
