Cancer Biotherapy and Radiopharmaceuticals最新文献

Background: For breast cancer staging, radiolabeled colloids and superparamagnetic iron oxide nanoparticles (SPIONs) are used for sentinel lymph node (SLN) imaging. This study characterized the intranodal activity distribution and absorbed dose distribution. Material and Methods: Six patients diagnosed with primary breast cancer were intradermally injected with ^99mTc-Nanocoll. The SLNs were resected, weighed, and measured for activity. Three groups of six rats were subcutaneously injected into the hind paw with either ^99mTc-Nanocoll, ^99mTc-SPIONs, or ⁶⁸Ga-SPIONs. Macro- and small-scale dosimetry calculations were performed using autoradiography images of cryosections of SLNs from patients and animals. Results: The mean absorbed dose in patient SLNs was 0.5 ± 0.3 mGy/MBq for ^99mTc-Nanocoll and 3.4 ± 1.8 mGy/MBq, assuming a ^99mTc-Nanocoll-based distribution of ⁶⁸Ga-SPIONs. Due to different decay characteristics, the heterogeneity in the absorbed dose differed between ^99mTc-SPIONs and ⁶⁸Ga-SPIONs with a maximum to mean absorbed dose ratio of 2.7 ± 0.3 and 1.6 ± 0.2, respectively. Conclusions: This study shows that ^99mTc- and ⁶⁸Ga-SPIONs and ^99mTc-nanocolloids have similar activity distribution in human and animal lymph nodes. Small-scale dosimetry models combined with clinical patient biokinetics may serve as a bridge between organ and tissue dosimetry and the interpretation of intrinsic geometric variation and its uncertainties in absorbed dose.

Objective: Optimize the treatment of extensive-stage small cell lung cancer (ES-SCLC). Materials and Methods: We collected data on patients with ES-SCLC who had stable disease (SD) after two cycles of first-line chemotherapy combined with immunotherapy (CIO) and subsequently received tailored treatment with anlotinib. The primary endpoints of the study were progression-free survival and overall survival (OS), while secondary endpoints included overall response rate (ORR), disease control rate (DCR), and adverse events (AEs). Results: A total of 45 patients were ultimately enrolled in the study. Preliminary analysis indicated that the integration of anlotinib provides promising efficacy for patients with ES-SCLC who had SD after two cycles of CIO. ORR and DCR were 26.67% and 62.22%, respectively, with median progression-free survival and median OS were 6.0 months and 10.0 months. Furthermore, subgroup analysis results showed that patients who experienced hypertension, proteinuria, and hand-foot syndrome during treatment had better efficacy. In addition, mechanistic analysis suggested that this regimen may activate the immune system by depleting immune suppression, thereby exerting a synergistic antitumor effect. Beyond the promising efficacy, the overall AEs of this regimen were manageable, indicating a potential positive outlook for this treatment model in this patient population. Conclusion: The adaptive treatment with anlotinib can significantly improve outcomes for these patients, with manageable toxicities, suggesting that this treatment model has the potential to become an important option for first-line therapy in ES-SCLC. However, its true clinical value requires further research for validation.

Background: Hyaluronic acid (HA), as a critical ingredient of extracellular matrix (ECM) and synovial fluid, has attracted extensive attention in targeted tumor thearpy. The superiority of HA is reflected as its great biocompatibility, biodegradability and special binding ability to CD44 receptor. Moreover, CD44 receptor proteins are overexpressed in many kinds of tumor cells and cancer stem cells (CSCs). Therefore, HA is commonly used as ligands for the surface modification of versatile nanocarriers applied in various tumor therapy approaches. Methods: We reviewed the literature and summarized the unique properties of HA, the rationale for the use of HA as tumor-specific carrier for drug delivery, catabolism of HA coated nanocarriers, and research achievements of frequently-used HA-modified organic and inorganic nanocarries. Results: We concluded the significant applications of HA coated nanocarriers in tumor chemotherapy and chemoresistance, combination therapy and cancer theranostics. Conclusion: The application prospect of HA-coated nanocarriers will be more extensive for various targeting combination therapy and theranostics.

Introduction: Integrin antagonist complex (IAC), a novel α_vβ₃ integrin antagonist peptidomimetic, has emerged as a promising agent for molecular imaging of tumor angiogenesis. This study evaluates the biodistribution and clinical efficacy of [⁶⁸Ga]Ga-DOTAGA-IAC PET/CT in detecting radioiodine-refractory differentiated thyroid carcinoma (RAIR-DTC), comparing its diagnostic performance with [¹⁸F]F-FDG PET/CT. Materials and Methods: In this prospective pilot study, RAIR-DTC patients underwent whole-body imaging with [¹⁸F] F-FDG PET/CT, followed by [⁶⁸Ga]Ga-DOTAGA-IAC PET/CT. Biodistribution patterns of [⁶⁸Ga]Ga-DOTAGA-IAC were assessed. Lesions with abnormal, nonphysiologic tracer uptake (showing activity exceeding mediastinal blood pool) were considered positive for disease. Imaging findings were compared between the two modalities, and quantitative metrics, including SUV_max, metabolic tumor volume, and total lesion glycolysis, were analyzed statistically. Results: Among 30 patients with RAIR-DTC, [⁶⁸Ga]Ga-DOTAGA-IAC PET/CT revealed predominant physiological tracer uptake in the kidneys. [¹⁸F]F-FDG PET/CT identified 97 lesions, predominantly nodal (73.2%), while [⁶⁸Ga]Ga-DOTAGA-IAC PET/CT detected 34 lesions, 50% of which were nodal. Few patients exhibited multiple lesions with varying uptake grades, with 20% showing coexisting higher-grade lesions (grade II or above) on [⁶⁸Ga]Ga-DOTAGA-IAC PET/CT. Conclusion: Angiogenesis imaging using [⁶⁸Ga]Ga-DOTAGA-IAC PET/CT demonstrates limited sensitivity for lesion detection in patients with RAIR-DTC compared with [¹⁸F]F-FDG PET/CT. However, the potential of [⁶⁸Ga]Ga-DOTAGA-IAC as a diagnostic tool for other cancers has been used in other cancers with positive imaging characteristics warranting further exploration.

Purpose: To evaluate the use of yttrium-90 (⁹⁰Y) dosimetry in predicting treatment outcomes when used following transarterial radioembolization with SIR-Spheres® (Resin ⁹⁰Y) in patients with hepatic tumors. Materials and Methods: This single institution retrospective analysis included 100 patients with hepatocellular carcinoma, colorectal carcinoma or other liver metastases who underwent transarterial radioembolization with resin ⁹⁰Y and had imaging follow-up within one year of treatment. Mean tumor dose and mean dose to nontumor was calculated using voxel-based dosimetry software. Descriptive statistics were reported and methods of analyses included simple and multivariable linear regression, contingency table analyses, Kaplan-Meier estimation, and Cox proportional hazards models. Results: Of 100 patients included, 65 demonstrated tumor shrinkage following transarterial radioembolization. Of these, 20 (30.8%) had hepatocellular carcinoma, 22 (33.8%) had colorectal carcinoma, and 23 (35.4%) had other types of metastases. There was an association between tumor shrinkage and mean tumor dose (p = 0.0285) and mean dose to nontumor (p = 0.0028) in hepatocellular carcinoma patients, but not colorectal carcinoma, or the other subgroup. For all 100 patients, time to death and mean tumor dose was associated only in the other subgroup (p = 0.0260), but not in the hepatocellular or colorectal carcinoma groups. Time to death and mean dose to nontumor was associated in hepatocellular carcinoma patients (p = 0.0421), but not the colorectal carcinoma or other subgroup. Conclusions: Voxel-based dosimetry assessment is a tool that may be utilized to assist in predicting treatment outcomes in responders to transarterial radioembolization.

Background: The cytotoxic effect of ²¹²Pb on microbial growth was examined, using six microorganisms, at clinically relevant time points, to determine the potency of ²¹²Pb as a self-sterilizing agent in radiopharmaceuticals using [²¹²Pb]Pb-DOTAMTATE. Materials and Methods: Vials of radiolabeled [²¹²Pb]Pb-DOTAMTATE, nonradiolabeled DOTAMTATE, and appropriate media were inoculated with Bacillus spizizenii, Candida albicans, Clostridium sporogenes, Pseudomonas aeruginosa, Staphylococcus aureus, or Aspergillus brasiliensis. Samples from each vial type were plated onto tryptic soy agar or Sabouraud dextrose plates and allowed to grow at optimal temperature for each strain to obtain quantifiable colony forming units (CFU). Results: Each microbial organism observed at least a 6 log reduction in total CFUs after 6 h of exposure to [²¹²Pb]Pb-DOTAMTATE drug product vials, showing no remaining colonies as compared to the vials containing only media and drug formulation with no radiolabeled material, utilizing a low absorbed dose of no greater than 1.01 kGy. A sterility assessment of the two [²¹²Pb]Pb-DOTAMTATE drug product vials containing the lowest total CFUs per vial displayed no microbial growth upon incubation for 14 d. Conclusions: This study suggests that ²¹²Pb in radiopharmaceuticals is a potent microbial cytotoxic agent with self-sterilizing properties.

Background: Secondary upper limb lymphedema commonly occurs after breast cancer surgery, for which treatment is limited. 9-cis-retinoic acid (9-cisRA) has been demonstrated to increase lymphangiogenesis without enhancing tumor metastasis but has disadvantages of poor water solubility, ready decomposition in light, instability to heat, and a short half-life. Methods: Based on this, 9-cisRA-Lip with a particle size of roughly 143 nm and high dispersibility was prepared by thin-film dispersion method and verified by Malvern Laser Particle Size Analyzer and electron microscopy. Results: In vitro, 9-cisRA-Lip demonstrated good biosafety and tumor safety, promoting the proliferation of L929 cells while having no effect on 4T1 and Human Umbilical Vein Endothelial (HUVEC) cells. Compared with 9-cisRA, 9-cisRA-Lip was more effective at stimulating mouse lymphatic endothelial cell (SVEC4-10) migration, proliferation, and tube formation. In vivo, 9-cisRA-Lip-Gel showed good slow release effect. Mice treated with 9-cisRA-Lip-Gel one-time local injection had considerably less tail edema than the control group from day 9 to day 39 postsurgery (p < 0.05). This may be attributed to the greater capacity of 9-cisRA-Lip to enhance the phosphorylation of FGFR3 (Fibroblast Growth Factor Receptor 3) at Tyr 724. Conclusions: 9-cisRA-Lip-Gel presents a potential treatment option for lymphedema following surgery.

Deep learning artificial intelligence (AI) algorithms are poised to subsume diagnostic imaging specialists in radiology and nuclear medicine, where radiomics can consistently outperform human analysis and reporting capability, and do it faster, with greater accuracy and reliability. However, claims made for generative AI in respect of decision-making in the clinical practice of theranostic nuclear medicine are highly contentious. Statistical computer algorithms cannot emulate human emotion, reason, instinct, intuition, or empathy. AI simulates intelligence without possessing it. AI has no understanding of the meaning of its outputs. The unique statistical probability attributes of large language models of AI must be complemented by the innate human intuitive capabilities of nuclear physicians who accept the responsibility and accountability for direct clinical care of each individual patient referred for theranostic management of specified cancers. Complementarity envisions synergistic engagement with AI radiomics, genomics, radiobiology, dosimetry, and data collation from multidimensional sources, including the electronic medical record, to enable the nuclear physician to spend informed face time with their patient. Together with physician discernment, application of the technical insights from AI will facilitate optimal formulation of a personalized precision theranostic strategy for empathic, efficacious, targeted treatment of the patient with cancer in accordance with their wishes.

[¹⁷⁷Lu]Lu-DOTATATE is a newly trending acceptable therapy in recurrent/residual meningioma with good safety. However, recognizing any possible side effects in this special population would be helpful for better management and individualization of this useful treatment. Although the seizure has been previously reported in a few cases after [¹⁷⁷Lu]Lu-DOTATATE therapy in recurrent meningioma, the acute onset of seizure in these patients, early after therapeutic radioligand administration, is not reported to the best of our knowledge. This report presents a case with the progression of residual meningioma after previous surgery in 2016 who developed with generalized tonic-clonic seizure, a few hours after administration of 200 mCi [¹⁷⁷Lu]Lu-DOTATATE. The patient was taking prophylactic doses of the lacosamide, although no previous history of seizure was reported.

Background: Methyltransferase-like 3 (METTL3) and HECT and RLD domain containing E3 ubiquitin protein ligase 4 (HERC4) have been studied in the field of oncology; however, their roles and interaction in hepatocellular carcinoma (HCC) await elucidation. Methods: Initially, METTL3 and HERC4 expressions in normal and HCC samples were predicted employing the UALCAN database, and the targeting relationship between these two was explored via coimmunoprecipitation assay. Following the quantification on N6-methyladenosine (m⁶A) enrichment, the localization of METTL3 and HERC4 on HCC cells was visualized via immunofluorescence assay. The effects of METTL3 and HERC4 on HCC cells proliferation and migration were determined in vitro assays. METTL3 and HERC4 expressions were quantified via quantitative polymerase chain reaction, and those of metastasis-related proteins N-cadherin and vimentin were calculated with immunoblotting assay. Furthermore, the levels of angiogenic factors such as vascular endothelial growth factor and basic fibroblast growth factor were measured by enzyme-linked immunosorbent assay. Results: METTL3 and HERC4 expressed highly in HCC and their expressions were positively correlated with tumor grade. METTL3 overexpression enhanced the expression of HERC4 and promoted the proliferation and migration abilities of HCC cells. Specifically, METTL3 overexpression increased vimentin and N-cadherin expressions, while its silencing did conversely. Besides, HERC4 overexpression reversed the effects of METTL3 silencing on the proliferation and migration as well as the levels of angiogenic factors in HCC cells. Conclusion: This study reveals the upregulation of METTL3 and HERC4 expression in HCC and their role in HCC by enhancing the proliferation, migration, and angiogenesis potential of HCC cells.