Quantitative imaging for targeted radionuclide therapy dosimetry : technical review

Targeted radionuclide therapy (TRT) is a promising technique for cancer therapy. However, in order to deliver the required dose to the tumor, minimize potential toxicity in normal organs, as well as monitor therapeutic effects, it is important to assess the individualized internal dosimetry based on patient-specific data. Advanced imaging techniques, especially radionuclide imaging, can be used to determine the spatial distribution of administered tracers for calculating the organ-absorbed dose. While planar scintigraphy is still the mainstream imaging method, SPECT, PET and bremsstrahlung imaging have promising properties to improve accuracy in quantification. This article reviews the basic principles of TRT and discusses the latest development in radionuclide imaging techniques for different theranostic agents, with emphasis on their potential to improve personalized TRT dosimetry

A multicentre comparison of quantitative 90Y PET/CT for dosimetric purposes after radioembolization with resin microspheres

Purpose: To investigate and compare the quantitative accuracy of Y-90 imaging across different generation PET/CT scanners, for the purpose of dosimetry after radioembolization with resin microspheres. Methods: A strict experimental and imaging protocol was followed by 47 international sites using the NEMA 2007/IEC 2008 PET body phantom with an 8-to-1 sphere-to-background ratio of Y-90 solution. The phantom was imaged over a 7-day period (activity ranging from 0.5 to 3.0 GBq) and all reconstructed data were analysed at a core laboratory for consistent processing. Quantitative accuracy was assessed through measures of total phantom activity, activity concentration in background and hot spheres, misplaced counts in a nonradioactive insert, and background variability. Results: Of the 69 scanners assessed, 37 had both time-of-flight (ToF) and resolution recovery (RR) capability. These current generation scanners from GE, Philips and Siemens could reconstruct background concentration measures to within 10 % of true values over the evaluated range, with greater deviations on the Philips systems at low count rates, and demonstrated typical partial volume effects on hot sphere recovery, which dominated spheres of diameter 20 mm in diameter, activity concentrations were consistently underestimated by about 20 %. Non-ToF scanners from GE Healthcare and Siemens were capable of producing accurate measures, but with inferior quantitative recovery compared with ToF systems. Conclusion: Current generation ToF scanners can consistently reconstruct Y-90 activity concentrations, but they underestimate activity concentrations in small structures (a parts per thousand currency sign37 mm diameter) within a warm background due to partial volume effects and constraints of the reconstruction algorithm. At the highest count rates investigated, measures of background concentration (about 300 kBq/ml) could be estimated on average to within 1 %, 5 % and 2 % for GE Healthcare (all-pass filter, RR + ToF), Philips (4i8s ToF) and Siemens (2i21s all-pass filter, RR + ToF) ToF systems, respectively. Over the range of activities investigated, comparable performance between GE Healthcare and Siemens ToF systems suggests suitability for quantitative analysis in a scenario analogous to that of postradioembolization imaging for treatment of liver cancer

Scintigraphic detection of TNF-driven inflammation by radiolabelled certolizumab pegol in patients with rheumatoid arthritis and spondyloarthritis

Background: Biologicals are the cornerstone for many treatment algorithms in inflammatory arthritis. While tumour necrosis factor (TNF) inhibitors may achieve important responses in similar to 50% of patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA), a significant fraction of patients are partial or non-responders. We hypothesised that in vivo assessment of TNF by scintigraphy with 99mTc-radiolabelled certolizumab pegol (CZP) might lead to a more 'evidence-based biological therapy'. Objectives: Our goal was to perform a proof-of-concept study of in vivo detection of TNF by immunoscintigraphy of a radiolabelled TNF inhibitor in RA and SpA, and correlate this with clinical, imaging findings and therapeutic outcome. Methods: CZP was conjugated with succinimidyl-6-hydrazino-nicotinamide and subsequently radiolabelled with Tc99m. Whole body and static images of hands, feet and sacroiliac joints of 20 patients (5 RA; 15 SpA) were acquired at 3 time points. Immunoscintigraphic findings were scored semiquantitatively. Subsequently, all patients were treated with CZP. Results: In peripheral joints, clinically affected joints or abnormal ultrasound findings were observed more frequently (p<0.001) in the scintigraphic-positive group. In patients with axial SpA, bone marrow edema on MRI was detected more frequently (p<0.001) in quadrants with tracer uptake. At the patient level, the odds of a joint remaining tender despite 24 weeks of CZP treatment was significantly smaller in joints with clear tracer uptake as compared with those with no uptake (OR=0.42, p=0.04). Conclusions: Immunoscintigraphy with radiolabelled CZP demonstrated both axial and peripheral inflammation, and displayed good correlation with clinical features, conventional imaging and therapy response

Transarterial RAdioembolization versus ChemoEmbolization for the treatment of hepatocellular carcinoma (TRACE) : study protocol for a randomized controlled trial

Background: Hepatocellular carcinoma is a primary malignant tumor of the liver that accounts for an important health problem worldwide. Only 10 to 15% of hepatocellular carcinoma patients are suitable candidates for treatment with curative intent, such as hepatic resection and liver transplantation. A majority of patients have locally advanced, liver restricted disease (Barcelona Clinic Liver Cancer (BCLC) staging system intermediate stage). Transarterial loco regional treatment modalities offer palliative treatment options for these patients; transarterial chemoembolization (TACE) is the current standard treatment. During TACE, a catheter is advanced into the branches of the hepatic artery supplying the tumor, and a combination of embolic material and chemotherapeutics is delivered through the catheter directly into the tumor. Yttrium-90 radioembolization (Y-90-RE) involves the transarterial administration of minimally embolic microspheres loaded with Yttrium-90, a beta-emitting isotope, delivering selective internal radiation to the tumor. Y-90-RE is increasingly used in clinical practice for treatment of intermediate stage hepatocellular carcinoma, but its efficacy has never been prospectively compared to that of the standard treatment (TACE). In this study, we describe the protocol of a multicenter randomized controlled trial aimed at comparing the effectiveness of TACE and Y-90-RE for treatment of patients with unresectable (BCLC intermediate stage) hepatocellular carcinoma. Methods/design: In this pragmatic randomized controlled trial, 140 patients with unresectable (BCLC intermediate stage) hepatocellular carcinoma, with Eastern Cooperative Oncology Group performance status 0 to 1 and Child-Pugh A to B will be randomly assigned to either Y-90-RE or TACE with drug eluting beads. Patients assigned to Y-90-RE will first receive a diagnostic angiography, followed by the actual transarterial treatment, which can be divided into two sessions in case of bilobar disease. Patients assigned to TACE will receive a maximum of three consecutive transarterial treatment sessions. Patients will undergo structural follow-up for a timeframe of two years post treatment. Post procedural magnetic resonance imaging (MRI) will be performed at one and three months post trial entry and at three-monthly intervals thereafter for two years to assess tumor response. Primary outcome will be time to progression. Secondary outcomes will be overall survival, tumor response according to the modified RECIST criteria, toxicities/adverse events, treatment related effect on total liver function, quality of life, treatment-related costs and cost-effectiveness

Surveillance or metastasis-directed Therapy for OligoMetastatic Prostate cancer recurrence (STOMP): study protocol for a randomized phase II trial

Background: Metastases-directed therapy (MDT) with surgery or stereotactic body radiotherapy (SBRT) is emerging as a new treatment option for prostate cancer (PCa) patients with a limited number of metastases (<= 3) at recurrence - so called "oligometastases". One of the goals of this approach is to delay the start of palliative androgen deprivation therapy (ADT), with its negative impact on quality of life. However, the lack of a control group, selection bias and the use of adjuvant androgen deprivation therapy prevent strong conclusions from published studies. The aim of this multicenter randomized phase II trial is to assess the impact of MTD on the start of palliative ADT compared to patients undergoing active surveillance. Methods/Design: Patients with an oligometastatic recurrence, diagnosed on choline PET/CT after local treatment with curative intent, will be randomised in a 1:1 ratio between arm A: active surveillance only and arm B: MTD followed by active surveillance. Patients will be stratified according to the location of metastasis (node vs. bone metastases) and PSA doubling time ( 3 months). Both surgery and SBRT are allowed as MDT. Active surveillance means 3-monthly PSA testing and re-imaging at PSA progression. The primary endpoint is ADT-free survival. ADT will be started in both arms at time of polymetastatic disease (>3 metastatic lesions), local progression or symptoms. The secondary endpoints include progression-free survival, quality of life, toxicity and prostate-cancer specific survival. Discussion: This is the first randomized phase 2 trial assessing the possibility of deferring palliative ADT with MDT in oligometastatic PCa recurrence