Thymotrinan

Determination of time‐integrated activity (TIA) with a reduced number of imaging sessions is essential for minimizing patient burden and clinical workload in the dosimetry of [ 177 Lu]Lu‐PSMA‐617. One approach to achieve this is by performing single‐time‐point (STP) dosimetry. However, STP dosimetry may be associated with significant accuracy errors in certain patients, potentially impacting the reliability of dose calculations. Moreover, the assessment of precision is crucial to evaluating the stability and reliability of estimated doses.

This study aims to investigate the accuracy and precision of few‐time‐points (FTP) TIA calculation in kidneys for [ 177 Lu]Lu‐PSMA‐617 using nonlinear mixed‐effects modeling (NLMEM).

Biokinetic data of kidneys from 63 patients with metastatic castration‐resistant prostate cancer (mCRPC) treated with [ 177 Lu]Lu‐PSMA‐617 in the first treatment cycle were used. The SPECT/CT measurement was done at time points (TP) 1) (1.8 ± 0.8) h, 2) (18.7 ± 0.9) h, 3) (42.6 ± 1.0) h, 4) (66.3 ± 0.9) h, and 5) (160.3 ± 24.2) h after injection. This study used the sum‐of‐exponentials function (SOEF) with six parameters, previously selected as the best fit function for the biokinetic data (PMID: 38423787). Reference TIAs (rTIAs) were derived from fitting the SOEF parameters to all‐time‐points (ATP) data within the NLMEM framework. Estimated TIAs (eTIAs) were calculated by fitting the FTP data, which consist of one‐, two‐, three‐, and four‐time points combinations of the biokinetic data. The accuracy of FTP‐NLMEM TIA calculations was quantified using the root‐mean‐square error (RMSE) and mean absolute percentage error (MAPE) of the relative deviation between eTIAs and rTIAs. Precision was assessed from the coefficient of variation (CV) of individual TIA estimates at each optimal time‐point combination.

For each optimal TP combination, the RMSEs and MAPEs were (11.0 ± 2.5)% and (7.0 ± 2.3)% for TP3, (6.3 ± 1.6)% and (4.8 ± 1.3)% for TP25, (3.9 ± 1.1)% and (2.3 ± 1.0)% for TP135, and (1.4 ± 0.8)% and (0.9 ± 0.8)% for TP1235. The %CV values of individual TIAs for each best TP combination were (17.1 ± 4.9)% for TP3, (8.5 ± 2.4)% for TP25, (6.3 ± 0.9)% for TP135, (5.1 ± 0.6)% for TP1235, and (4.4 ± 0.3)% for ATP.

The accuracy and precision of various FTP schemes have been determined and can be used to decide on the number of measurements required. Our study showed that incorporating TP3 in FTP dosimetry could lead to a high accuracy and precision of calculated individual TIAs in [ 177 Lu]Lu‐PSMA‐617therapy.

Neuropathic pain has multiple etiologies, and many patients remain inadequately treated. The cyclic adenosine monophosphate (cAMP) signaling pathway plays a critical role in inflammatory responses, particularly through the upregulation of proinflammatory cytokines. This study aimed to investigate the anti-inflammatory and analgesic properties of the marine-derived antimicrobial peptide Tilapia Piscidin 3 (TP3), using a chronic constriction injury (CCI) model to simulate neuropathic pain. In vitro assays showed that TP3 exerted a dose-dependent inhibitory effect on lipopolysaccharide-induced proinflammatory cytokine expression in mouse BV-2 microglia and RAW 264.7 macrophages. Nociceptive behavioral tests revealed that intrathecal (IT) administration of TP3 alleviated CCI-induced mechanical allodynia and thermal hyperalgesia. Immunofluorescence analysis showed that IT TP3 significantly increased phosphodiesterase 4D (PDE4D) levels and decreased the expression of cAMP, brain-derived neurotrophic factor (BDNF), and tumor necrosis factor-α in astrocytes within the dorsal horn of the spinal cord in CCI rats. The antinociceptive effects of TP3 were abolished by the PDE4D inhibitor rolipram, highlighting the role of PDE4D-mediated modulation of the cAMP pathway in producing these effects. These findings suggest that TP3 may be a promising therapeutic agent for treating neuropathic pain by exerting anti-inflammatory and analgesic effects through regulation of the cAMP pathway.