Dosing Therapeutic Radiopharmaceuticals in Obese Patients

The prevalence of obesity has increased dramatically in the Western population. Obesity is known to influence not only the proportion of adipose tissue but also physiological processes that could alter drug pharmacokinetics. Yet, there are no specific dosing recommendations for radiopharmaceuticals in this patient population. This could potentially lead to underdosing and thus suboptimal treatment in obese patients, while it could also lead to drug toxicity due to high levels of radioactivity. In this review, relevant literature is summarized on radiopharmaceutical dosing and pharmacokinetic properties, and we aimed to translate these data into practical guidelines for dosing of radiopharmaceuticals in obese patients. For radium-223, dosing in obese patients is well established. Furthermore, for samarium-153-ethylenediaminetetramethylene (EDTMP), dose-escalation studies show that the maximum tolerated dose will probably not be reached in obese patients when dosing on MBq/kg. On the other hand, there is insufficient evidence to support dose recommendations in obese patients for rhenium-168-hydroxyethylidene diphosphonate (HEDP), sodium iodide-131, iodide 131-metaiodobenzylguanidine (MIBG), lutetium-177-dotatate, and lutetium-177-prostate-specific membrane antigen (PSMA). From a pharmacokinetic perspective, fixed dosing may be appropriate for these drugs. More research into obese patient populations is needed, especially in the light of increasing prevalence of obesity worldwide

A meta-analysis on the diagnostic performance of whole-body MRI for the initial staging of Hodgkin lymphoma in children and adults using FDG-PET/CT as a reference standard

Background: Staging of Hodgkin lymphoma is important for determining prognosis and treatment planning. The current gold standard is FDG-PET/CT, but WB-MRI could be a radiation free alternative. Objective: A meta-analysis of all published data on the diagnostic performance of WB-MRI for the initial staging of Hodgkin lymphoma using FDG-PET/CT as a reference standard. Evidence Acquisition: Both the PubMed/MEDLINE and EMBASE databases were systematically searched (updated until March 14, 2023) for studies that compared WB-MRI with FDG-PET/CT for staging Hodgkin lymphoma. The “quality assessment of diagnostic accuracy studies” tool (QUADAS-2) was used to assess methodological quality. Pooled staging accuracy, sensitivity and specificity of WB-MRI compared to FDG-PET/CT was calculated for determining stage and for both nodal and extra-nodal staging. A sensitivity analysis for children and adults was performed. Evidence Synthesis: A total of nine studies with a combined total of 297 Hodgkin lymphoma patients were included. Pooled sensitivity and specificity for nodal staging were 94% (95%CI 0.92–0.96) and 99% (95%CI 0.98–1.00) respectively. For extra-nodal staging sensitivity and specificity were 90% (95%CI 0.74–0.96) and 100% (95%CI 0.99–1.00). For disease stage, the pooled accuracy was 92% for pediatric studies (95%CI 0.86–0.96), 94% for adult studies (95%CI 0.87–0.97) and 92% (95%CI 0.87–0.96) for all studies combined. Conclusion: When using FDG-PET/CT as a reference standard, WB-MRI shows high sensitivity and specificity for both nodal and extra-nodal staging and for determining disease stage both in children and adults. Clinical Impact: WB-MRI could be used as a good radiation-free alternative for FDG-PET/CT in Hodgkin lymphoma staging

Lutetium-177-PSMA therapy for prostate cancer patients—a brief overview of the literature

Radioligand therapy with lutetium-177 prostate specific membrane antigen ([177Lu]Lu-PSMA) represents a promising treatment for metastatic castration-resistant prostate cancer patients. In this paper, we aim to summarize the current knowledge derived from the literature as well as the authors’ experiences on [177Lu]Lu-PSMA therapy. Various systematic reviews, mostly including small retrospective studies, summarized efficacy and oncological outcomes of [177Lu]Lu-PSMA therapy. Any therapy-related prostate-specific antigen (PSA) response was reported in the majority of the patients (68–75%); >50% PSA decline was demonstrated in 34.5–51% of the patients. Incidence of side effects was low and in most patients, hematological toxicity remained limited to Common Terminology Criteria for Adverse Events (CTCAE) grade 1–2. Also, favorable efficacy was shown with regard to tumor response on imaging, pain symptoms and quality of life. In the near future, results of the awaited pivotal prospective studies (NCT03511664, NCT03392428) will define efficacy of [177Lu]Lu-PSMA therapy and its oncological value for metastatic castration-resistant prostate cancer patients

A compact and mobile hybrid C-arm scanner for simultaneous nuclear and fluoroscopic image guidance

Purpose: This study evaluates the performance of a mobile and compact hybrid C-arm scanner (referred to as IXSI) that is capable of simultaneous acquisition of 2D fluoroscopic and nuclear projections and 3D image reconstruction in the intervention room. Results: The impact of slightly misaligning the IXSI modalities (in an off-focus geometry) was investigated for the reduction of the fluoroscopic and nuclear interference. The 2D and 3D nuclear image quality of IXSI was compared with a clinical SPECT/CT scanner by determining the spatial resolution and sensitivity of point sources and by performing a quantitative analysis of the reconstructed NEMA image quality phantom. The 2D and 3D fluoroscopic image of IXSI was compared with a clinical CBCT scanner by visualizing the Fluorad A+D image quality phantom and by visualizing a reconstructed liver nodule phantom. Finally, the feasibility of dynamic simultaneous nuclear and fluoroscopic imaging was demonstrated by injecting an anthropomorphic phantom with a mixture of iodinated contrast and 99mTc. Conclusion: Due to the divergent innovative hybrid design of IXSI, concessions were made to the nuclear and fluoroscopic image qualities. Nevertheless, IXSI realizes unique image guidance that may be beneficial for several types of procedures. Key Points: • IXSI can perform time-resolved planar (2D) simultaneous fluoroscopic and nuclear imaging. • IXSI can perform SPECT/CBCT imaging (3D) inside the intervention room

Current status of yttrium-90 microspheres radioembolization in primary and metastatic liver cancer

Liver malignancy, including primary liver cancer and metastatic liver cancer has become one of the most common causes of cancer-related death worldwide due to the high malignant degree and limited systematic treatment strategy. Radioembolization with yttrium-90 (90Y)-loaded microspheres is a relatively novel technology that has made significant progress in the local treatment of liver malignancy. The different steps in the extensive work-up of radioembolization for patients with an indication for treatment with 90Y microspheres, from patient selection to follow up, both technically and clinically, are discussed in this paper. It describes the application and development of 90Y microspheres in the treatment of liver cancer

Use of an anti-reflux catheter to improve tumor targeting for holmium-166 radioembolization—a prospective, within-patient randomized study

Purpose: The objective of this study was to investigate whether the use of an anti-reflux catheter improves tumor targeting for colorectal cancer patients with unresectable, chemorefractory liver metastases (mCRC) treated with holmium-166 (166Ho)-radioembolization. Materials and methods: In this perspective, within-patient randomized study, left and right hepatic perfusion territories were randomized between infusion with a Surefire® anti-reflux catheter or a standard microcatheter. The primary outcome was the difference in tumor to non-tumor (T/N) activity distribution. Secondary outcomes included the difference in infusion efficiency, absorbed doses, predictive value of 166Ho-scout, dose-response relation, and survival. Results: Twenty-one patients were treated in this study (the intended number of patients was 25). The median T/N activity concentration ratio with the use of the anti-reflux catheter was 3.2 (range 0.9–8.7) versus 3.6 (range 0.8–13.3) with a standard microcatheter. There was no difference in infusion efficiency (0.04% vs. 0.03% residual activity for the standard microcatheter and anti-reflux catheter, respectively) (95%CI − 0.05–0.03). No influence of the anti-reflux catheter on the dose-response rate was found. Median overall survival was 7.8 months (95%CI 6–13). Conclusion: Using a Surefire® anti-reflux catheter did not result in a higher T/N activity concentration ratio in mCRC patients treated with 166Ho-radioembolization, nor did it result in improved secondary outcomes measures. Trial registration: clinicaltrials.gov identifier: NCT0220880

Current Status and Future Direction of Hepatic Radioembolisation.

Radioembolisation is a locoregional treatment modality for hepatic malignancies. It consists of several stages that are vital to its success, which include a pre-treatment angiographic simulation followed by nuclear medicine imaging, treatment activity choice, treatment procedure and post-treatment imaging. All these stages have seen much advancement over the past decade. Here we aim to provide an overview of the practice of radioembolisation, discuss the limitations of currently applied methods and explore promising developments

Advances in Radionuclide Therapies for Patients with Neuro-endocrine Tumors

Purpose of Review: To provide insights into the role of peptide receptor radionuclide therapy (PRRT) in patients with advanced neuroendocrine tumors (NET) and an overview of possible strategies to combine PRRT with locoregional and systemic anticancer treatments. Recent Findings: Research on combining PRRT with other treatments encompasses a wide variety or treatments, both local (transarterial radioembolization) and systemic therapies, chemotherapy (i.e., capecitabine and temozolomide), targeted therapies (i.e., olaparib, everolimus, and sunitinib), and immunotherapies (e.g., nivolumab and pembrolizumab). Furthermore, PRRT shows promising first results as a treatment prior to surgery. Summary: There is great demand to enhance the efficacy of PRRT through combination with other anticancer treatments. While research in this area is currently limited, the field is rapidly evolving with numerous ongoing clinical trials aiming to address this need and explore novel therapeutic combinations

Evaluating the Targeting of a Staphylococcus-aureus-Infected Implant with a Radiolabeled Antibody In Vivo

Implant infections caused by Staphylococcus aureus are difficult to treat due to biofilm formation, which complicates surgical and antibiotic treatment. We introduce an alternative approach using monoclonal antibodies (mAbs) targeting S. aureus and provide evidence of the specificity and biodistribution of S.-aureus-targeting antibodies in a mouse implant infection model. The monoclonal antibody 4497-IgG1 targeting wall teichoic acid in S. aureus was labeled with indium-111 using CHX-A”-DTPA as a chelator. Single Photon Emission Computed Tomography/computed tomographyscans were performed at 24, 72 and 120 h after administration of the 111In-4497 mAb in Balb/cAnNCrl mice with a subcutaneous implant that was pre-colonized with S. aureus biofilm. The biodistribution of this labelled antibody over various organs was visualized and quantified using SPECT/CT imaging, and was compared to the uptake at the target tissue with the implanted infection. Uptake of the 111In-4497 mAbs at the infected implant gradually increased from 8.34 %ID/cm3 at 24 h to 9.22 %ID/cm3 at 120 h. Uptake at the heart/blood pool decreased over time from 11.60 to 7.58 %ID/cm3, whereas the uptake in the other organs decreased from 7.26 to less than 4.66 %ID/cm3 at 120 h. The effective half-life of 111In-4497 mAbs was determined to be 59 h. In conclusion, 111In-4497 mAbs were found to specifically detect S. aureus and its biofilm with excellent and prolonged accumulation at the site of the colonized implant. Therefore, it has the potential to serve as a drug delivery system for the diagnostic and bactericidal treatment of biofilm