Imageable Brachytherapy with Chelator-Free Radiolabeling Hydrogel.

Brachytherapy stands as an essential clinical approach for combating locally advanced tumors. Here, an injectable brachytherapy hydrogel is developed for the treatment of both local and metastatic tumor. Fe-tannins nanoparticles are efficiently and stably radiolabeled with clinical used therapeutic radionuclides (such as 131I, 90Y, 177Lu, and 225Ac) without a chelator, and then chemically cross-linked with 4-armPEG-SH to form brachytherapy hydrogel. Upon intratumoral administration, magnetic resonance imaging (MRI) signal from ferric ions embedded within the hydrogel directly correlates with the retention dosage of radionuclides, which can real-time monitor radionuclides emitting short-range rays in vivo without penetration limitation during brachytherapy. The hydrogel's design ensures the long-term tumor retention of therapeutic radionuclides, leading to the effective eradication of local tumor. Furthermore, the radiolabeled hydrogel is integrated with an adjuvant to synergize with immune checkpoint blocking therapy, thereby activating potent anti-tumor immune responses and inhibiting metastatic tumor growth. Therefore, this work presents an imageable brachytherapy hydrogel for real-time monitoring therapeutic process, and expands the indications of brachytherapy from treatment of localized tumors to metastatic tumors.

Organic photoredox catalyzed C(sp3)-H functionalization of saturated aza-heterocycles via a cross-dehydrogenative coupling reaction.

Herein we present a novel protocol to access α-functionalized saturated aza-heterocycles, and a variety of nucleophilic groups, such as indole, naphthol, phenol, pyrrole, furyl, nitromethyl, and cyano, could be easily installed into saturated aza-heterocycles. Furthermore, a range of biologically valuable 3,3'-diindolylmethane derivatives could also be readily accessed under mild photocatalytic conditions.

A Radioluminescent Metal-Organic Framework for Monitoring 225Ac in Vivo.

225Ac is considered as one of the most promising radioisotopes for alpha-therapy because its emitted high-energy α-particles can efficiently damage tumor cells. However, it also represents a significant threat to healthy tissues owing to extremely high radiotoxicity if targeted therapy fails. This calls for a pressing requirement of monitoring the biodistribution of 225Ac in vivo during the treatment of tumors. However, the lack of imageable photons or positrons from therapeutic doses of 225Ac makes this task currently quite challenging. We report here a nanoscale luminescent europium-organic framework (EuMOF) that allows for fast, simple, and efficient labeling of 225Ac in its crystal structure with sufficient 225Ac-retention stability based on similar coordination behaviors between Ac3+ and Eu3+. After labeling, the short distance between 225Ac and Eu3+ in the structure leads to exceedingly efficient energy transduction from225Ac-emitted α-particles to surrounding Eu3+ ions, which emits red luminescence through a scintillation process and produces sufficient photons for clearcut imaging. The in vivo intensity distribution of radioluminescence signal originating from the 225Ac-labeled EuMOF is consistent with the dose of 225Ac dispersed among the various organs determined by the radioanalytical measurement ex vivo, certifying the feasibility of in vivo directly monitoring 225Ac using optical imaging for the first time. In addition, 225Ac-labeled EuMOF displays notable efficiency in treating the tumor. These results provide a general design principle for fabricating 225Ac-labeled radiopharmaceuticals with imaging photons and propose a simple way to in vivo track radionuclides with no imaging photons, including but not limited to 225Ac.

Differential diagnosis of lung cancer and tuberculosis based on 18 F-fluorodeoxyglucose PET/CT multi-time points imaging.

OBJECTIVE: To investigate the value of 18 F-fluorodeoxyglucose(FDG) PET/CT multi-time points imaging (MTPI) on the differential diagnosis between lung cancer (LC) and tuberculosis (TB). METHODS: Sixty-four patients underwent 18 F-FDG PET/CT MTPI. The stdSUVmax, stdSUVavg, retention index, metabolic tumor volume, total lesion glycolysis at four-time points and slope of metabolic curve were measured and calculated, and the sex, age, and uniformity of FDG uptake were recorded. The difference in each index between LC and TB was analyzed, and dynamic metabolic curves (DMCs) of LC and TB were fitted by significance indexes. Artificial neural network (ANN) prediction models were established between squamous cell carcinoma (SCC) and TB, as well as between adenocarcinomas and TB. RESULTS: Differences between SCC and TB, stdSUVmax/avg at four-time points, total lesion glycolysis, stdSUVmax/avg slope (1-2 h,1-3 h and 1-4 h), uniformity of FDG uptake and age were significant. stdSUVavg has the largest area under the 4 h curve; age was only significant between adenocarcinomas and TB. DMCs at 1-4 h fitted by stdSUVavg were more helpful in differentiating LC and TB than stdSUVmax. stdSUVavg(1 h and 4 h), stdSUVavg slope 1-4 h, age, and uniformity of FDG uptake were selected to establish an ANN prediction model between SCC and TB; the area under the curve (AUC) was 100.0%. The same indices were used to establish the prediction model between adenocarcinomas and TB; the AUC was up to 83.5, and after adding stdSUVavg (2 and 4 h) to adenocarcinomas and TB models, the AUC was 87.7%. CONCLUSION: 18 F-FDG PET/CT MTPI fitting DMCs and establishing an ANN prediction model would distinguish SCC from TB relatively accurately and provide certain help in the differentiation between adenocarcinomas and TB.

18F-FDG PET/CT for staging and response assessment of primary parotid MALT lymphoma with multiple sites involvement: A case report.

RATIONALE: Mucosa-associated lymphoid tissue (MALT) lymphoma is an extranodal low-grade B cell lymphoma that generally exhibits an indolent clinical course. Currently, the application of F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) in MALT lymphoma is still controversial. Herein, we reported a case of using F-FDG PET/CT for staging and response assessment of primary parotid MALT lymphoma with multiple sites involvement. As far as we know, there are no similar case reports have been published before. PATIENT CONCERNS: A 71-year-old woman, who received mass resection twice during the past 2 years due to the repeatedly relapse of facial painless masses and diagnosed as reactive lymphoid hyperplasia by pathologic tests. However, the pathological diagnosis was then changed to primary parotid MALT lymphoma after left parotidectomy operation because of a new mass found in her left parotid. Four months later, the right eyelid of the patient swelled with a blurred vision. Then, F-FDG PET/CT scan was performed for staging, and the imaging results showed an abnormal increase of F-FDG uptake in multiple sites including bilateral ocular adnexal, lungs, pleura, occipital subcutaneous tissue, left kidney, and lymph nodes. DIAGNOSES: The patient was diagnosed as primary parotid MALT lymphoma with Ann Arbor stage of IVA based on the F-FDG PET/CT findings. INTERVENTIONS: The patient received 4 cycles of chemotherapy, followed by a partial metabolic remission (PMR), which was determined by interim F-FDG PET/CT, and finally additional 2 cycles of chemotherapy. OUTCOMES: The follow-up study illustrated that the patient had been alive and doing well at 12 months after chemotherapy. LESSONS: Although MALT lymphoma normally localizes in the primary organs, the involvement of multiple organs and lymph nodes is possible. The use of PET/CT demonstrated significant clinical values in the accurate staging and response assessment of F-FDG-avid MALT lymphoma. It is potentially useful for indicating the progress and transformation of MALT lymphoma, and guidance in localization of pathological biopsy. It is also helpful for clinicians to choose reasonable treatment strategy and improve the prognosis of patients.