Purpose Gadolinium-neutron capture therapy (Gd-NCT) employs isotopically enriched Gadolinium (Gd) and thermal neutrons to selectively target cancer cells. This study investigated the targeting efficacy of ¹⁵⁷Gd-DOTA-PSMA (Prostate-Specific Membrane Antigen) in prostate cancer and explored its potential applications in Gd-NCT. Methods and results We developed ¹⁵⁷Gd-DOTA-PSMA, a novel theranostic bio-gadolinium agent specifically designed for magnetic resonance imaging (MRI)-guided Gd-NCT. ⁶⁸ Ga-DOTA-PSMA positron emission tomography-computed tomography (PET/CT) imaging showed peak radiotracer uptake at 2 h post-injection, with a tumor-to-non-tumor (T/NT) ratio of 6.95 ± 0.60. MRI analysis confirmed a stable T₁ signal enhancement 2 h post-injection. Time-of-flight inductively coupled plasma mass spectrometry (TOF-ICP-MS) revealed significantly elevated Gd concentrations in 22Rv1 tumor compared to PC-3 tumor and other healthy organs. ICP-MS analysis showed Gd concentrations of 165.69 μg [Gd]/g in 22Rv1 tumors and 35.25 μg [Gd]/g in blood, yielding a tumor-to-blood (T/B) ratio of 4.65 ± 0.54 and a T/NT ratio of 3.65 ± 0.49. Neutron irradiation with ¹⁵⁷Gd-DOTA-PSMA reduced cell viability, inhibited colony formation, and induced DNA damage and apoptosis in 22Rv1 cells. In 22Rv1 mice, γ-H2AX levels peaked at 6 h post-irradiation, accompanied by an increase in pro-apoptotic proteins and a decrease in anti-apoptotic proteins over 24 h. In the NCT group following the injection of ¹⁵⁷Gd-DOTA-PSMA, there was effective suppression of tumor growth without a loss of body weight, resulting in a 1.7-fold increase in median survival compared to control group. Conclusions ¹⁵⁷Gd-DOTA-PSMA, as a theranostic bio-gadolinium agent designed for targeted Gd-NCT in prostate cancer, represents a novel therapeutic approach and broadens the scope of potential applications of neutron capture therapy. Graphical abstract

Stroke is a severe health problem, and magnetic resonance imaging (MRI) plays a significant role in stroke. To investigate the clinical value of MRI T2-mapping in carotid artery plaque. To locate the plaque in the carotid artery, 25 patients with carotid atherosclerosis were examined by 3.0-T MRI with three-dimensional (3D) time-of-flight and 3D fast spin-echo (FSE) T1-weighted scanning. The original images were obtained after T2-mapping (multi-spin-echo sequence) scanning. The T2 values of the plaque in the narrowest lumen were measured on T2 maps after postprocessing of the original images. Based on the symptoms, the patients were divided into two sub-groups; independent sample t-test was employed to compare the difference between the T2 values of the plaque in the two groups. We evaluated the optimal threshold and diagnostic efficacy of T2 values in predicting cerebrovascular symptoms by the receiver operating characteristic (ROC) curve. The T2 values of the carotid artery plaque in symptomatic and asymptomatic patients were 111.43 ± 46.54 ms and 59.25 ± 39.77 ms, respectively (t = −3.421, P < 0.01). ROC analysis showed that the T2 value of 65.38 ms was the optimal threshold to predict cerebrovascular symptoms. The specificity, sensitivity, and accuracy attained were 94.1% (16/17), 93.3% (14/15), and 93.8% (30/32), respectively. We quantitatively assessed carotid plaque components by MRI T2-mapping technology. The T2 values of the carotid plaque were associated with cerebrovascular symptoms. The T2 values of the symptomatic plaque group were significantly higher than those of the asymptomatic group.

Gadolinium-neutron capture therapy (Gd-NCT) employs Gadolinium (Gd) isotopes and thermal neutrons to specifically target and kill cancer at cells level. This study investigates the targeting efficacy of ¹⁵⁷Gd-DOTA-HK (DHK), a novel agent designed for Gd-NCT and MRI. We synthesized ¹⁵⁷Gd-DHK, which combines a Gd-DOTA complex as a neutron capturer and MRI probe with αvβ6 binding peptide (HK) for targeted Pancreas adenocarcinoma (PDAC) therapy. ¹⁵⁷Gd-DHK demonstrated a significantly high binding affinity for BxPC-3 cells. scintigraphy revealed that the optimal time window for Gd-NCT was 26 h after injection. The conjugate's imaging capabilities and its potential as an MRI contrast agent were validated. The conjugate effectively triggered nuclear reactions via Gd-NCT, leading to efficient tumor cell destruction. Photon sensitization studies showed that ¹⁵⁷Gd-DHK induced photon-mediated phototoxicity in cancer cells while exhibiting minimal toxicity. ¹⁵⁷Gd-DHK shows great potential as a theranostic agent for targeted imaging of PDAC and Gd-NCT applications. It presents a novel strategy to enhance the specificity and efficacy of Gd-NCT in cancer treatment.