EANM guideline for radionuclide therapy with radium-223 of metastatic castration-resistant prostate cancer.

Radium Ra-223 dichloride (radium-223, Xofigo®) is a targeted alpha therapy approved for the treatment of castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastatic disease. Radium-223 is the first targeted alpha therapy in this indication providing a new treatment option, with evidence of a significant survival benefit, both in overall survival and in the time to the first symptomatic skeletal-related event. The skeleton is the most common metastatic site in patients with advanced prostate cancer. Bone metastases are a clinically significant cause of morbidity and mortality, often resulting in bone pain, pathologic fracture, or spinal cord compression necessitating treatment. Radium-223 is selectively accumulated in the bone, specifically in areas of high bone turnover, by forming complexes with the mineral hydroxyapatite (the inorganic matrix of the bone). The alpha radiation generated during the radioactive decay of radium-223 produces a palliative anti-tumour effect on the bone metastases. The purpose of this guideline is to assist nuclear medicine specialists in evaluating patients who might be candidates for treatment using radium-223, planning and performing this treatment, understanding and evaluating its consequences, and improving patient management during therapy and follow-up.

Optimized 124I PET dosimetry protocol for radioiodine therapy of differentiated thyroid cancer.

UNLABELLED: Iodine kinetics and lesion dose per administered 131I activity (LDpA) of differentiated thyroid cancer metastases were determined using 124I PET. These data were analyzed to derive an optimized dosimetry protocol. METHODS: We evaluated the time-activity-concentration curves of 37 lesions in 17 patients who had undergone thyroidectomies. LDpA determination involved 124I PET images acquired at 4, 24, 48, 72, and 96 h after intake of a capsule containing 20-40 MBq of 124I. A combination of a linear and a monoexponential or a monoexponential function only parameterized the time-activity-concentration curves. The LDpAs, calculated using data from all 5 PET time points, served as reference. The lesions were classified into 3 groups, according to potential for cure with 131I therapy: low (< or =5 Gy GBq(-1); n = 14), medium (between 5 and 10 Gy GBq(-1); n = 9), or high LDpAs (>10 Gy GBq(-1); n = 14). Using the reference approach, the differences in the empiric kinetic parameters within the LDpA groups were evaluated. The reference LDpAs were compared with those derived from only 2, 3, or 4 PET data points and from 1 adapted 2-point approach. Lin's concordance correlation coefficient (rho c) and the mean absolute percentage deviation in LDpAs were used to assess agreement between simplified and reference approaches. RESULTS: The effective 124I half-life, linear activity-concentration rate (alpha), and 24-h activity concentration (CpA) (the latter 2 per administered 124I activity) differed significantly among the LDpA groups (P < 0.05). LDpAs correlated with 24-h CpAs (r = 0.94, P < 0.001). Using the 4-, 24-, and 96-h measurements, a rho c value of greater than or equal to 0.90 was found, and the mean absolute percentage deviation was less than or equal to 16%. Similar statistical values were obtained for the adapted approach, which was based on 24- and 96-h PET data points only. CONCLUSION: Lesion classification into LDpA groups was feasible using a single PET scan at approximately 24 h. Because of the highly variable kinetics, 1 additional measurement at approximately 96 h was needed to obtain a sufficiently reliable LDpA estimate. The adapted 24-96-h approach appears to be the optimal 124I protocol and is a reliable simplification of the 5-point protocol.

Pretherapeutic 124I dosimetry reliably predicts intratherapeutic blood kinetics of 131I in patients with differentiated thyroid carcinoma receiving high therapeutic activities.

AIM: The aim of this study was to assess the agreement between predicted blood uptake values using I and actually measured I blood uptake values (reference) in patients with differentiated thyroid carcinoma receiving largely high therapeutic activities. PATIENTS AND METHODS: Fourteen patients were analyzed retrospectively, who underwent a series of both pretherapeutic and intratherapeutic blood sampling using median I activities of 23 MBq and median therapy I activities of 10 GBq. Data of five blood samples from each patient were analyzed. Lin's concordance correlation coefficient analysis was carried out to assess the kinetic agreement. The time-integrated I activity coefficient (TIAC) for the blood compartment and the effective I clearance time (ECT), expressed as effective I half-life on the basis of a monoexponential model, were ascertained. For each patient, the (intrapatient) percentage differences between pretherapeutic and intratherapeutic TIACs and ECTs were calculated. The (interpatient) difference in TIACs and ECTs between pretherapy and intratherapy groups was evaluated using the Mann-Whitney U-test. RESULTS: Lin's concordance correlation coefficient was at least 0.97, indicating substantial kinetic agreement between pretherapeutic and intratherapeutic radioiodine kinetics. The mean (median)±SD (range) of the absolute percentage difference was 9% (11%)±7% (0.33-20%) for the TIAC and 11% (10%)±10% (0-23%) for the ECT. A slightly higher median TIAC was observed in intratherapy (2.8 vs. 3.3 h), but this was not statistically significant (P=0.15), whereas no remarkable ECT difference (P=0.62) was found. CONCLUSION: The pretherapeutic blood kinetics derived from diagnostic I activities provides a reliable estimation of the intratherapeutic I blood kinetics in patients receiving largely high therapy activities, showing its potential for radioiodine treatment planning.

[Therapy of bone metastases with radium-223. German guidelines]. / Radionuklidtherapie von Knochenmetastasen mittels Radium-223. DGN-Handlungsempfehlung.

This document describes the guideline for therapy of bone metastases with radium-223 ((223)Ra) published by the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften in Germany (AWMF) under the auspices of the Deutsche Gesellschaft für Nuklearmedizin (DGN), Östereichische Gesellschaft für Nuklearmedizin (OGN), and Schweizerische Gesellschaft für Nuklearmedizin (SGNM). This guidance is based on an interdisciplinary consensus. These recommendations are a prerequisite for the quality management in the treatment of patients with bone metastases from prostate cancer using (223)Ra. They are aimed at guiding nuclear medicine specialists in selecting candidates to receive therapy and to deliver the treatment in a safe and effective manner. The document contains background information and definitions. It covers the rationale, indications and contraindications for therapy with (223)Ra. Essential topics are the requirements for institutions performing the therapy, which patient data have to be available prior to performance of therapy, and how treatment has to be carried out technically and organisationally. Moreover, essential elements of follow-up and aftercare are specified. As a matter of principle, the treatment inclusive aftercare has to be realised in close cooperation with the involved medical disciplines.