Cancer Biotherapy and Radiopharmaceuticals最新文献

Purpose: To explore the efficacy and safety of ¹²⁵I source implantation via a coaxial puncture in treating locally advanced pancreatic cancer (LAPC).

Methods: A retrospective analysis was used to investigate the efficacy and safety of 40 patients with LAPC treated with radioactive ¹²⁵I particles under CT guidance in the hospital. A treatment planning system was used to develop the preoperative plan, and the radioactive ¹²⁵I particles were implanted using a coaxial puncture technique in the same plane to simulate a sector distribution system. CT scans were performed at postoperative months 2, 4, and 6 for follow-up treatment outcome assessment. Overall survival (OS) time and progression-free survival (PFS) were calculated, and factors affecting prognosis were assessed.

Results: All patients completed the operation successfully. The overall response rate of treatment at 2, 4, and 6 months was 37.5%, 47.5%, and 50.0%. The median OS and PFS were 11.0 months (95% confidence interval [CI]: 9.14-12.86) and 9.0 months (95% CI: 7.45-10.55), respectively. The 6- and 12-month PFS rates were 85.0% (95% CI: 69.6%-93.0%) and 35.0% (95% CI: 20.8%-49.5%), respectively. The 12-month OS rates were 47.5% (95% CI: 20.2%-49.8%). The intraoperative complications related to the operation were local abdominal hemorrhage in 2 cases, subcutaneous soft tissue hematoma in 2 cases, and wrong puncture of the pancreatic duct in 1 case. The main side-effects were fever in 10 cases and decreased appetite in 3 cases in the recent postoperative period. Eighteen grade 0 cases and 3 cases of grade I acute radiation enteritis occurred. No acute radiation damage above grade II and late radiation damage was observed.

Conclusions: Coaxial puncture ¹²⁵I source implantation is a promising percutaneous minimally invasive technology that is safe and effective in treating LAPC.

Background: Boron neutron capture therapy (BNCT) is a precision binary radiotherapy. In this modality, thermal neutrons combine with 10B to induce a nuclear reaction that kills tumor cells. Its therapeutic efficacy depends on the targeted accumulation of boron delivery agents. BNCT has demonstrated clinical efficacy in treating head and neck cancers and recurrent gliomas. However, there is limited evidence regarding its application in hepatocellular carcinoma (HCC). This review systematically examines recent advances in novel boron carriers. It also assesses the potential of BNCT for treating HCC and aims to provide a new therapeutic option for HCC.

Methods: We used a systematic research approach to investigate the latest advances in novel boron carrier development. We also analyzed existing clinical data related to BNCT treatment for HCC. We aimed to systematically assess the feasibility and potential of applying BNCT to HCC.

Results: Newly designed boron carriers show significantly enhanced targeted aggregation within tumor cells and reduced systemic toxicity compared to traditional carriers. Preliminary clinical studies have confirmed the potential efficacy of BNCT in inhibiting HCC growth. Notably, BNCT possesses the unique advantage of precise tumor targeting, which shows promising potential in minimizing damage to surrounding normal liver tissue.

Conclusion: The progress made in the development of boron carriers has built a solid foundation for improving the efficacy and safety of BNCT treatment for HCC. By addressing current limitations in boron delivery and clinical evidence, BNCT has the potential to complement existing treatment modalities, improve outcomes for HCC patients, and provide new directions for the clinical treatment of HCC.

Background: Intense hepatobiliary uptake of [^99mTc]Tc-sestamibi in myocardial perfusion scintigraphy (MPS) often degrades image quality by obscuring the inferior myocardial wall, leading to equivocal studies. While nonpharmacological interventions are inconsistent, the choleretic agent ursodeoxycholic acid (UDCA) could potentially accelerate hepatic clearance. The effectiveness of a convenient, single-dose UDCA intervention has not been rigorously evaluated. This study determines if a single oral dose of UDCA administered shortly before imaging could significantly improve hepatic clearance and enhance image quality in MPS.

Methods: In this prospective, randomized, double-blind, placebo-controlled trial, 174 patients undergoing 1 d MPS were randomized. The intervention group (n = 87) received a single 300 mg oral dose of UDCA, whereas the control group (n = 87) received an identical placebo (300 mg vitamin C) 1 h before the stress radiotracer injection. All participants and interpreting physicians were blinded. Primary end points were the semiquantitative liver-to-background (L/B) and myocardium-to-liver (M/L) ratios from SPECT images.

Results: Baseline characteristics were well-matched. The primary analysis revealed no statistically significant benefit from UDCA. The mean L/B ratio was 1.82 ± 0.45 in the UDCA group versus 1.89 ± 0.52 in the placebo group (p = 0.48). The mean M/L ratio was 1.15 ± 0.31 versus 1.11 ± 0.29, respectively (p = 0.41). A post hoc power analysis revealed the study was underpowered to detect a small effect size.

Conclusions: A single 300 mg oral dose of UDCA administered 1 h before stress imaging does not significantly improve hepatic clearance of [^99mTc]Tc-sestamibi or enhance M/L ratios. This is likely due to a pharmacokinetically insufficient regimen, as a single dose is unlikely to achieve the necessary biliary concentration for a significant choleretic effect. Future research should focus on alternative interventions or optimized UDCA dosing schedules, such as multiday protocols, combined with advanced imaging techniques like SPECT/CT, to conclusively determine effective strategies for improving MPS image quality.

Chemotherapy, radiation, and targeted biological treatments are examples of cancer therapies that have a significant effect on the immune system. They frequently interfere with the manufacture of immunoglobulins (Igs), which results in immunodeficiency. The processes via which these medications affect B cell activity and antibody production are examined in this review, with an emphasis on cytokine regulation, bone marrow suppression, and therapy-induced lymphopenia. Reduced Ig levels can have clinical repercussions such as increased vulnerability to infections, decreased effectiveness of vaccinations, and compromised immune monitoring. This study also looks at new and existing methods to lessen these consequences, including immunomodulatory techniques, prophylactic antibiotics, and Ig replacement treatment. Optimizing patient outcomes, striking a balance between immunological protection and oncologic efficacy, and directing future research in supportive cancer care all depend on an understanding of how humoral immunity and cancer treatment interact.

Purpose: This study evaluated the correlations between findings from ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET), contrast-enhanced magnetic resonance imaging (MRI), and diffusion-weighted imaging (DWI) for hepatocellular carcinoma (HCC) lesions, and differences in imaging features between the infiltrative and noninfiltrative morphological subtypes of HCC were investigated.

Methods: In this retrospective study, 79 patients with HCC imaged with hepato-specific contrast-enhanced dedicated liver PET/MRI were included. Patients were grouped as positive or negative based on MRI, and the sensitivity and specificity of PET imaging were calculated. In addition, patients were classified as infiltrative and noninfiltrative, and tumor SUV, metabolic tumor volume, total lesion glycolysis (TLG), and apparent diffusion coefficient (ADC) variables were compared. Correlations between SUV, tumor size, and ADC values were investigated through regression analyses. Linear regression analyses were used to investigate the relationships between DWI-/PET-derived variables and serum alfa-feto protein (AFP) levels.

Results: A total of 79 patients were included in the study. PET imaging demonstrated 77% sensitivity and 88% specificity, and 19 (27%) patients had infiltrative morphology. The infiltrative subgroup showed a higher rate of portal venous tumor thrombosis (79%), and most tumor thrombi (79%) were ¹⁸F-FDG-avid. A significant relationship was observed between tumor SUV values, ADCmin, and tumor size. Serum AFP levels correlated with SUV_peak (R² = 0.223) and TLG (R² = 0.283; both p < 0.001) values.

Conclusions: Higher ¹⁸F-FDG uptake was observed in infiltrative lesions compared with noninfiltrative ones. The majority of malignant tumor thrombi exhibited increased ¹⁸F-FDG uptake. Although the ability of ¹⁸F-FDG PET to detect HCC lesions is limited by the variable uptake in HCC tumors, it proves valuable in assessing tumor aggressiveness.

Postphenomenology examines the cultural dimension of human-technology relations whereby innovations, such as artificial intelligence (AI), re/shape our behavior and relation to reality. Generative AI is amoral and uncaring, but it is mediating evolutionary changes in human cognitive function, consciousness, and behavior. The role of phronesis, in the preservation of human values in the face of ChatGPT challenges, is explored here through the lens of theranostic nuclear oncology practice. Phronesis involves moral grounding, epistemic humility, and the integration of cognitive, affective, and contextual social expertise. Empathic, efficient care of the individual patient requires judicious symbiosis between the formidable epistemic capabilities of large language models, particularly in radiogenomics, radiomolecular biology, and tumor radiation dosimetry, and compassionate, responsible, accountable personal care by the doctor. Being cognizant of the strengths and limitations of AI, and the critical role of phronesis in personalized patient care, the physician can ensure optimal theranostic clinical oncology outcomes of human-AI collaboration.

Cluster of differentiation 44 (CD44), a versatile transmembrane glycoprotein, plays a crucial role in the progression, metastasis, and therapeutic resistance of colorectal cancer (CRC). This review clarifies CD44's essential function in CRC via connections with the extracellular matrix (ECM), particularly hyaluronic acid (HA), and important signaling pathways, such as Ras/mitogen-activated protein kinase/extracellular signal-regulated kinase and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt). The overexpression of CD44, especially its variant isoforms (CD44v), is associated with aggressive tumor characteristics, increased cancer stem cell (CSC) traits, and unfavorable outcomes in CRC patients. CD44 enhances tumor cell attachment, movement, infiltration, and epithelial-mesenchymal transition, facilitating metastasis and resistance to chemotherapy. Its interactions with ECM elements and receptors, such as the epidermal growth factor receptor, enhance tumor growth and survival signaling. Therapeutic approaches aimed at CD44, such as monoclonal antibodies, small interfering RNAs, and nanoparticles targeting CD44 (e.g., CSA-SS-CXB@CPT, A@HAP), show encouraging antitumor effectiveness by interrupting CD44-HA interactions and the subsequent signaling pathways. Preclinical studies emphasize the benefits of pairing anti-CD44 therapies with PI3K/Akt or Wnt/β-catenin inhibitors to improve results. This review combines CD44's molecular mechanisms, isoform-specific functions, and CSC regulation in CRC, highlighting the potential as a biomarker and therapeutic target to enhance patient outcomes.

Background: Cyclooxygenase-2 (COX-2) serves as a pivotal molecule bridging inflammation and tumor development, playing a central role in the initiation, progression, and malignant transformation of colorectal adenomas.

Methods: This review systematically examines COX-2 expression patterns, molecular regulatory networks, and its potential applications in clinical diagnosis, prognosis assessment, and chemoprevention.

Results: Evidence indicates that COX-2 exhibits significantly elevated expression in adenoma tissues (e.g., 54.8% positive rate in polyps vs. 18.5% in adjacent tissue), driving pathological progression through multiple mechanisms including cell proliferation induction, apoptosis inhibition, angiogenesis promotion, and tumor immune microenvironment remodeling. Nonsteroidal anti-inflammatory drugs and selective COX-2 inhibitors have demonstrated clear promise in adenoma chemoprevention (with agents such as celecoxib reducing advanced adenoma recurrence risk by 33%-45%).

Conclusions: COX-2 is a critical early-event biomarker and therapeutic target in colorectal adenomas. Targeting the COX-2 pathway represents a viable strategy for prevention, although challenges regarding safety and personalized application remain.

Background: Lung cancer is the biggest reason of cancer-correlated death worldwide, owing primarily to immune evasion and poor response to current immunotherapies. Objective: The aim of this work was focused on the immunomodulatory effect of histone deacetylase 4 (HDAC4) in tumor immunological milieu, specifically CD8⁺ T cell trafficking. Methods: Quantitative RT-PCR, immunofluorescence labeling, and FISH tests were used to determine HDAC4 and CXCR3 expression and location in lung cancer tissues. Flow cytometry assessed CD8⁺ T cell function, and histological analysis revealed tumor development. Results: Our results showed that HDAC4 was highly overexpressed in lung tumor samples, and it was associated with advanced clinical stage, lymph node metastases, and a worse overall survival rate. HDAC4 decreased CXCR3 expression, affecting CD8⁺ T cell infiltration and effector function. HDAC4 knockdown increased CD8⁺ T cell cytotoxicity, whereas CXCR3 inhibition reversed this effect. HDAC4 expression predicted poor survival with a ROC AUC of 0.78. SB939 treatment raised CXCR3 expression by 2.4 times and CD8⁺ infiltration by 39%. Conclusion: These findings point to HDAC4 as a crucial epigenetic regulator of immune cell trafficking in lung cancer. Given the growing interest in ultrasound-assisted medication delivery and immunological priming, our findings point to HDAC4 as a viable therapeutic target in ultrasound-guided immunomodulatory methods for lung cancer.

Introduction: α-emitting radiopharmaceuticals are increasingly being evaluated as potential cancer therapeutics. In this study, the authors evaluated the distribution of thorium-227 (²²⁷Th) and its first daughter nuclide, radium-223 (²²³Ra), by analyzing tissue activity data from monkey studies from different antibody-based targeted thorium conjugates (hereafter called "conjugates"). This study clarified the extent of elimination by physical decay and redistribution from tissues for both radionuclides. Methods: In monkey biodistribution studies for four different conjugates, animals were sacrificed at multiple time points, and organ activities of ²²⁷Th and ²²³Ra were measured by direct γ counting. These values were compared to the maximally expected organ activities based on physical decay as the sole elimination path to evaluate the impact of redistribution from tissues. Whole-body activities in cancer patients, measured with high-purity germanium detectors during a first-in-human study of a CD22-targeting conjugate, were evaluated similarly to determine whether they aligned with the overall patterns seen in tissue data. Results: The integrated analysis demonstrated that for all conjugates, the physical decay appeared to be the main elimination path for ²²⁷Th without a strong redistribution from organs, whereas ²²³Ra shows a fast and strong redistribution (≥90%) from most of the tissues except for bone (∼0%) and (large) intestine. The lack of redistribution from bone as well as the high radioactivity in the intestine is consistent with data obtained with ²²³Ra chloride in monkeys and humans. These findings were independent of the assessed compound, target, dose, and administered activity. The observation in monkeys that physical decay is the main elimination path for ²²⁷Th and that ²²³Ra undergoes a fast additional elimination in a typical tissue was consistent with clinical whole-body radioactivity data. Conclusions: The overarching consistency of the findings regarding tissue redistribution of ²²⁷Th and ²²³Ra across different conjugates and the consistency with clinical observations of whole body radioactivity in patients emphasize the importance of considering the potential redistribution of long-lived daughter nuclides of radionuclides used in therapeutic applications in humans.