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The radiation absorbed dose to blood and organs from activity in the blood is relevant for nuclear medicine dosimetry and for research in biodosimetry. The present study provides coefficients for the average absorbed dose rates to the blood from blood-borne activity for radionuclides frequently used in targeted radiotherapy and in PET diagnostics. The results were deduced from published data for vessel radius-dependent dose rate coefficients and reasonable assumptions on the blood-volume distribution as a function of the vessel radius. Different parts of the circulatory system were analyzed separately. Vessel size information for heart chambers, aorta, vena cava, pulmonary artery, and capillaries was taken from published results of morphometric measurements. The remaining blood not contained in the mentioned vessels was assumed to reside in fractal-like vascular trees, the smallest branches of which are the arterioles or venules. The applied vessel size distribution is consistent with recommendations of the ICRP on the blood-volume distribution in the human. The resulting average absorbed dose rates to the blood per nuclear disintegration per milliliter (ml) of blood are (in 10−11 Gy·s−1·Bq−1·ml) Y-90: 5.58, I-131: 2.49, Lu-177: 1.72, Sm-153: 2.97, Tc-99m: 0.366, C-11: 4.56, F-18: 3.61, Ga-68: 5.94, I-124: 2.55. Photon radiation contributes 1.1–1.2·10−11 Gy·s−1·Bq−1·ml to the total dose rate for positron emitters but significantly less for the other nuclides. Blood self-absorption of the energy emitted by ß-particles in the whole blood ranges from 37% for Y-90 to 80% for Tc-99m. The correspondent values in vascular trees, which are important for the absorbed dose to organs, range from 30% for Y-90 to 82% for Tc-99m. [ABSTRACT FROM AUTHOR]

This document provides the new EANM guideline on radioiodine therapy of benign thyroid disease. Its aim is to guide nuclear medicine physicians, endocrinologists, and practitioners in the selection of patients for radioiodine therapy. Its recommendations on patients' preparation, empiric and dosimetric therapeutic approaches, applied radioiodine activity, radiation protection requirements, and patients follow-up after administration of radioiodine therapy are extensively discussed., (© 2023. The Author(s).)

Desmoplastic small round cell tumor (DSRCT) is a rare, radiosensitive, yet difficult-to-treat sarcoma subtype affecting predominantly male adolescents. Extensive intraperitoneal seeding is common and requires multimodal management. With no standard therapy established, the prognosis remains poor, and new treatment options are needed. We demonstrate the clinical potential of C-X-C motif chemokine receptor 4 (CXCR4)-directed imaging and endoradiotherapy in DSRCT. Methods: Eight male patients underwent dual-tracer imaging with [ 18 F]FDG and CXCR4-directed [ 68 Ga]pentixafor PET/CT. A visual comparison of both tracers, along with uptake quantification in active DSRCT lesions, was performed. [ 68 Ga]pentixafor uptake was correlated with immunohistochemical CXCR4 expression on tumor cells. Four patients with end-stage progressive disease underwent CXCR4-based endoradiotherapy. We report the safety, response by RECIST 1.1, and survival after endoradiotherapy. Results: Uptake of [ 68 Ga]pentixafor in tumor lesions was demonstrated in all patients with DSRCT, providing diagnostic power comparable to [ 18 F]FDG PET. Corresponding CXCR4 expression was confirmed by immunohistochemistry in all DSRCT biopsies. Finally, 4 patients were treated with CXCR4-directed [ 90 Y]endoradiotherapy, 3 in a myeloablative dose range with subsequent autologous stem cell transplantation. All 3 required transfusions, and febrile neutropenia occurred in 2 patients (resulting in 1 death). Notably, severe nonhematologic adverse events were absent. We observed signs of response in all 3 patients, translating into disease stabilization in 2 patients for 143 and 176 d, respectively. In the third patient, postmortem autopsy confirmed a partial pathologic response. Conclusion: We validated CXCR4 as a diagnostic biomarker and a promising target for endoradiotherapy in DSRCT, demonstrated its feasibility, and provided the first evidence of its clinical efficacy., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

In radionuclide therapy, activity kinetics in tissues determine the absorbed doses administered and thus efficacy and side effects of treatment. The objective of this work was to derive expressions for the parameters affecting the absorbed dose to a target tissue for first-order activity kinetics. The activity uptake results from contributions from the first-pass activity flow through the target tissue preceding systemic equilibration and uptake after distribution of the administered compound in the body. The absorbed dose from uptake after equilibration is the product of the mean energy deposited per decay in the target tissue, the time integral of the plasma activity concentration, the plasma volume flow per unit target tissue mass, the probability of activity removal during passage, and the mean lifetime of activity in the target tissue. Quantitative analysis of the determinants of absorbed dose exemplarily for radioiodine therapy indicates that the high uptake often observed in Graves' disease must be associated with high tissue perfusion and removal probability and that administration of stable iodine increases mean lifetime. For therapies with long residence times of the active compound in the blood, such as radioiodine therapy, the contribution of the first-pass is small compared with uptake after equilibration. The relative first-pass contribution is higher for agents that are rapidly eliminated from the blood pool, such as radiolabelled somatostatin analogues, and may dominate after arterial application. Understanding the determining parameters in radionuclide therapy reveals dose-limiting factors and opens up opportunities to optimise and individualize therapy, potentially improving treatment success rates., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier GmbH.)

C-X-C motif chemokine receptor 4 (CXCR4)-targeted radioligand therapy (RLT) has already been applied to advanced blood cancers, such as multiple myeloma or diffuse large B-cell lymphoma. We present a series of patients with advanced T-cell lymphoma (TCL) who were scheduled for CXCR4-directed therapy as a conditioning regimen, followed by hematopoietic stem cell transplantation (HSCT). Methods: Four patients with advanced, heavily pretreated, and relapsed TCL (2 men, 2 women; median age, 50 y) without suitable alternative therapeutic options underwent CXCR4-directed PET and pretherapeutic dosimetry. We then conducted CXCR4-targeted RLT in combination with allogeneic (3/4, 75%) or autologous (1/4, 25%) HSCT. One patient also underwent radioimmunotherapy targeting CD66 to enhance therapeutic efficacy. We investigated safety, best response, progression-free survival, and overall survival. Results: Pretherapeutic dosimetry indicated lymphoma-absorbed doses of up to 33.2 Gy from CXCR4-targeted RLT. Except for 1 patient who developed tumor lysis syndrome along with transient grade 3 kidney failure, no acute toxicity, allergic reactions, or other adverse events were recorded during therapy. One patient developed septicemia and subsequently died 16 d after RLT, whereas engraftment was achieved in the remaining 3 patients (75%). During follow-up, a partial response was recorded in 1 of 3 patients (33.3%) and a complete metabolic response in the other two (66.7%, with 1 patient also receiving additional radioimmunotherapy). Median progression-free survival was 7 mo (range, 4-25 mo). After a median follow-up of 54 mo (range, 4-56 mo), 3 patients were still alive at the date of censoring. Conclusion: For advanced, heavily pretreated TCL, CXCR4-directed RLT may serve as an effective conditioning therapy before HSCT and can cause substantial antilymphoma activity, leading to a remarkable response in selected cases., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

A growing body of literature reports on the upregulation of C-X-C motif chemokine receptor 4 (CXCR4) in a variety of cancer entities, rendering this receptor as suitable target for molecular imaging and endoradiotherapy in a theranostic setting. For instance, the CXCR4-targeting positron emission tomography (PET) agent [ 68  Ga]PentixaFor has been proven useful for a comprehensive assessment of the current status quo of solid tumors, including adrenocortical carcinoma or small-cell lung cancer. In addition, [ 68  Ga]PentixaFor has also provided an excellent readout for hematological malignancies, such as multiple myeloma, marginal zone lymphoma, or mantle cell lymphoma. PET-based quantification of the CXCR4 capacities in vivo allows for selecting candidates that would be suitable for treatment using the theranostic equivalent [ 177 Lu]/[ 90 Y]PentixaTher. This CXCR4-directed theranostic concept has been used as a conditioning regimen prior to hematopoietic stem cell transplantation and to achieve sufficient anti-lymphoma/-tumor activity in particular for malignant tissues that are highly sensitive to radiation, such as the hematological system. Increasing the safety margin, pretherapeutic dosimetry is routinely performed to determine the optimal activity to enhance therapeutic efficacy and to reduce off-target adverse events. The present review will provide an overview of current applications for CXCR4-directed molecular imaging and will introduce the CXCR4-targeted theranostic concept for advanced hematological malignancies., (© 2022. The Author(s).)

The chemokine receptor 4 (CXCR4), which is overexpressed in many solid and hematologic malignancies, can be targeted for radiopeptide therapy via the antagonist pentixather. The biokinetics and dosimetry of 177 Lu-pentixather and 90 Y-pentixather were analyzed in this study. Methods: This retrospective study was a standardized reevaluation of data collected for treatment planning. Nineteen patients with complete sets of planar whole-body scans over at least 4 d and a single SPECT/CT scan after administration of 200 MBq of 177 Lu-pentixather were included. Kinetics were measured in the whole body, in tissues with activity retention, and in 10 individuals in the blood. Time-integrated activity coefficients and tissue-absorbed doses were derived. Results: Increased uptake of pentixather was observed in the kidneys, liver, spleen, and bone marrow, inducing respective median absorbed doses of 0.91 Gy (range, 0.38-3.47 Gy), 0.71 Gy (range, 0.39-1.17 Gy), 0.58 Gy (range, 0.34-2.26 Gy), and 0.47 Gy (range, 0.14-2.33 Gy) per GBq of 177 Lu-pentixather and 3.75 Gy (range, 1.48-12.2 Gy), 1.61 Gy (range, 1.14-2.97 Gy), 1.66 Gy (range, 0.97-6.69 Gy), and 1.06 Gy (range, 0.27-4.45 Gy) per GBq of 90 Y-pentixather. In most tissues, activity increased during the first day after the administration of 177 Lu-pentixather and afterward decayed with mean effective half-lives of 41 ± 10 h (range, 24-64 h) in the kidneys and median half-lives of 109, 86, and 92 h in the liver, spleen, and bone marrow, respectively. Maximum uptake per kidney was 2.2% ± 1.0% (range, 0.6%-5.1%). In organs showing no specific uptake, absorbed doses exceeding 0.3 Gy/GBq of 90 Y-pentixather were estimated for the urinary bladder and for tissues adjacent to accumulating organs such as the adrenal glands, bone surface, and gallbladder. Dose estimates for tumors and extramedullary lesions ranged from 1.5 to 18.2 Gy/GBq of 90 Y-pentixather. Conclusion: In patients with hematologic neoplasms, absorbed doses calculated for bone marrow and extramedullary lesions are sufficient to be effective as an adjunct to high-dose chemotherapies before stem cell transplantation., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Context: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with limited treatment options. Theranostic approaches with adrenal specific radiotracers hold promise for improved diagnostics and treatment., Objective: Here, we report a new theranostic approach to advanced ACC applying (R)-1-[1-(4-[123I]iodophenyl)ethyl]-1H-imidazole-5-carboxylic acid azetidinyl amide ([123I]IMAZA) for diagnostic imaging and [131I]IMAZA for radionuclide therapy., Methods: Sixty-nine patients with nonresectable, metastatic ACCs were screened using a diagnostic [123I]IMAZA scan. Patients with significant uptake in all tumoral lesions were offered treatment with [131I]IMAZA. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1), and adverse effects were assessed by Common Toxicity Criteria (version 5.0)., Results: After screening, 13 patients were treated with a median of 25.7 GBq [131I]IMAZA (range 18.1-30.7 GBq). Five individuals received a second treatment course. Best response was a decrease in the RECIST target lesions of -26% in 2 patients. Five patients with disease stabilization experienced a median progression-free survival of 14.3 months (range 8.3-21.9). Median overall survival in all patients was 14.1 months (4.0-56.5) after therapy. Treatment was well tolerated, in other words no severe toxicities (CTCAE grade ≥3) were observed., Conclusion: In patients with advanced ACC refractory to standard therapeutic regimens, [131I]IMAZA treatment was associated with disease stabilization and nonsignificant tumor size reduction in a significant patient fraction and only limited toxicities. High [131I]IMAZA-uptake in tumor lesions was observed in 38.5% of patients with advanced ACC, rendering [131I] IMAZA a potential treatment option in a limited, well-defined patient fraction. Further clinical trials will be necessary to evaluate the full potential of this novel theranostic approach., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Without any doubt, high dose radiation exposure can induce hypothyroidism. However, there are open questions related to the mechanisms of its induction, corresponding dose thresholds and possible countermeasures. Therefore, this review addresses the aetiology, prevention and therapy of radiation induced hypothyroidism. External beam radiotherapy with several 10 Gy to the head and neck region and radioiodine therapy with several 100 Gy thyroid absorbed dose can destroy the thyroid gland and can induce autoantibodies against thyroid tissue. According to recent literature, clinical hypothyroidism is observed at threshold doses of ∼10 Gy after external beam radiotherapy and of ∼50 Gy after radioiodine therapy, children being more sensitive than adults. In children and adolescents exposed by the Chernobyl accident with mean thyroid absorbed doses of 500-800 mGy, subclinical hypothyroidism has been detected in 3%-6% of the cases with significant correlation to thyroid absorbed doses above 2.5 Gy. In case of nuclear emergencies, iodine thyroid blocking (ITB) is the method of choice to keep thyroid absorbed doses low. Large doses of stable iodine affect two different steps of internalization of radioiodine (transport and organification); perchlorate affecting the transport only may be an alternative to iodine. Administered before radioiodine incorporation, the effect of 100 mg iodide or more is still about 90% after 1 days, 80% after 2 days, and 50% or less after 3 days. If administered (too) late after exposure to radioiodine, the theoretically expected protective effect of ITB is about 50% after 6 h, 25% after 12 h, and about 6% after 24 h. In case of repeated or continuous exposure, repeated administration of 50 mg of iodide daily is indicated. If radiation-induced hypothyroidism cannot be avoided, thyroid hormone replacement therapy with individualized dosing and regular monitoring in order to maintain thyroid-stimulating hormone levels within the normal range ensures normal life expectancy., (© 2021 Society for Radiological Protection. Published on behalf of SRP by IOP Publishing Limited. All rights reserved.)

Purpose: The radiolabelled somatostatin analogue [ 177 Lu]Lu-DOTA-EB-TATE binds to albumin via Evans blue, thereby increasing the residence time in the blood and potentially allowing more therapeutic agent to be absorbed into the target tissue during peptide receptor radionuclide therapy. It was tested in selected patients whether the substance is superior to [ 177 Lu]Lu-DOTA-TOC., Methods: Activity kinetics in organs and tumours after [ 177 Lu]Lu-DOTA-EB-TATE and [ 177 Lu]Lu-DOTA-TOC were compared intraindividually in five patients with progressive somatostatin receptor-positive disease scheduled for radionuclide therapy., Results: In comparison to [ 177 Lu]Lu-DOTA-TOC, tumour doses per administered activity were higher for [ 177 Lu]Lu-DOTA-EB-TATE in 4 of 5 patients (median ratio: 1.7; range: 0.9 to 3.9), kidney doses (median ratio: 3.2; range: 1.6 to 9.8) as well as spleen doses (median ratio: 4.7; range 1.2 to 6.2) in all patients, and liver doses in 3 of 4 evaluable patients (median ratio: 4.0; range: 0.7 to 4.9). The tumour to critical organs absorbed dose ratios were higher after [ 177 Lu]Lu-DOTA-TOC in 4 of 5 patients., Conclusions: Prior to a treatment with [ 177 Lu]Lu-DOTA-EB-TATE, it should be assessed individually whether the compound is superior to established substances.

Purpose: Neurofibromatosis type 2 (NF2) is a genetic disorder that is associated with multiple tumors of the nervous system, and approximately one half of patients present with meningiomas. For patients with multifocal disease, somatostatin receptor-targeted peptide receptor radionuclide therapy (PRRT) might be a suitable systemic treatment option., Patients and Methods: Between March 2015 and August 2017, 11 NF2 patients (7 females and 4 males; mean age, 39 ± 12 years) with multifocal, progressive meningiomas underwent a median of 4 cycles of PRRT (range, 2-6 cycles). Acute and chronic adverse events were recorded according to National Institutes of Health's Common Toxicity Criteria (CTC) version 5.0. Follow-up MRIs (every 3 to 6 months), using the Response Assessment in Neuro-Oncology response criteria for meningiomas, were used to assess treatment responses., Results: Peptide receptor radionuclide therapy was well tolerated in all patients without any relevant acute adverse effects. Transient hematologic toxicity (CTC grade 3) was observed in 2 subjects. Somatostatin receptor-directed radiopeptide therapy resulted in radiological disease stabilization in 6 of 11 patients. Median progression-free survival was 12 months (range, 1-55 months), and overall survival was 37 months (range, 5-61 months)., Conclusions: Based on our retrospective pilot data, PRRT is feasible and well-tolerated in NF2 patients. It might offer a suitable treatment option in subjects with multiple, recurrent, or treatment-refractory meningiomas., Competing Interests: Conflicts of interest and sources of funding: This publication was funded by the Interdisciplinary Center of Clinical Research (IZKF) and the University of Würzburg in the funding program Open Access Publishing. None declared to all authors., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The combination of somatostatin receptor-directed peptide receptor radionuclide therapy (PRRT) in combination with external beam radiotherapy (EBRT) might prove a feasible treatment option in patients with advanced meningioma., Patients and Methods: From May 2010 to May 2011, 10 patients with unresectable meningioma (6 × WHO grade I, 2 × WHO grade II, 2 × WHO grading not available) were treated with one cycle of PRRT followed by EBRT. Long-term toxicity and efficacy were assessed according to Common Terminology Criteria for Adverse Events version 5.0 and magnetic resonance imaging-based Response Assessment in Neuro-Oncology Working Group criteria, respectively., Results: During long-term follow-up of a median of 105.0 months (range, 38.2-111.4 m), combined PRRT and EBRT was well-tolerated with no severe acute or chronic toxicity. Kidney or bone marrow function was not affected in any patient. Combination of PRRT and EBRT resulted in disease stabilization in 7 of the 10 patients with a median progression-free survival of 107.7 months (range, 47.2-111.4 m) vs. 26.2 months (range, 13.8-75.9 m) for the patients with meningioma progression., Conclusions: The combination of PRRT and EBRT is a feasible and safe therapeutic option in meningioma patients. In this pilot cohort, the multimodality treatment demonstrated good disease stabilization., (© 2020 The Authors.)

The chemokine receptor CXC-chemokine receptor 4 (CXCR4) is a transmembrane receptor involved in survival, proliferation, and dissemination of different cancers, including hematopoietic malignancies. Relapsed or refractory hematopoietic cancers are frequently resistant to conventional therapy, and novel highly active strategies are urgently needed. CXCR4-directed endoradiotherapy constitutes a highly promising targeted therapeutic concept. Here, we investigated the adverse effects of this novel treatment approach. Methods: Twenty-two patients with heavily pretreated lymphoproliferative or myeloid malignancies were treated with 177 Lu- or 90 Y-pentixather-a CXCR4-directed therapeutic radioligand-before conventional conditioning therapy followed by autologous or allogeneic hematopoietic stem cell transplantation. Twenty-five CXCR4-directed endoradiotherapies were administered to those patients. Adverse events occurring between endoradiotherapy and the start of conventional conditioning therapy were retrospectively analyzed and graded for the estimation of the safety profile. Results: CXCR4-directed endoradiotherapy with pentixather showed a favorable toxicity profile. As expected, the hematopoietic system was most affected, with all subjects developing cytopenias. Except for 1 acute kidney failure, grade 3, due to tumor lysis syndrome, overall nephro- and hepatotoxicity was low. Other higher-grade adverse events were either transient and resolved or easily manageable. Conclusion: Therapy with radiolabeled pentixather appears to be well tolerated and easily applicable when preceding conventional conditioning regimens for hematopoietic stem cell transplantation., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: PET/CT with both C-choline and C-methionine has recently been reported to offer advantages over F-FDG for imaging in multiple myeloma (MM). The aim of this study was to directly compare the diagnostic performance of both non-FDG radiotracers in MM patients., Methods: Nineteen patients with a history of MM (n = 18) or solitary bone plasmacytoma (n = 1) underwent both C-choline and C-methionine PET/CT for diagnostic imaging. In this retrospective analysis, scans were compared on a patient and on a lesion basis. In 12 patients, respective tracer uptake in the iliac crest was correlated with the extent of malignant bone marrow plasma cell infiltration., Results: C-methionine detected more intramedullary MM lesions in 8 (42.1%) of 19 patients. In the remainder (11/19 [57.9%]), both C-choline and C-methionine provided equal results. C-methionine demonstrated higher lesion-to-muscle ratios (P = 0.0001). In the 12 patients in whom a recent bone marrow biopsy was available, SUVmean as well as SUVmax correlated significantly with the degree of malignant plasma cell infiltration for both C-methionine (SUVmean: r = 0.85, P < 0.001; SUVmax: r = 0.82, P = 0.001) and C-choline (SUVmean: r = 0.72, P < 0.008; SUVmax: r = 0.73; P = 0.006)., Conclusions: Our data suggest that C-methionine PET/CT might be more sensitive than C-choline PET/CT for the detection of active MM lesions.

Purpose: As has been previously reported, the somatostatin receptor (SSTR) imaging agent [ 68 Ga]-labeled 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotate ([ 68 Ga]DOTATATE) demonstrates lower uptake in normal organs in patients with a high neuroendocrine tumor (NET) burden. Given the higher SSTR affinity of [ 68 Ga] DOTATATE, we aimed to quantitatively investigate the biodistribution of [ 68 Ga]-labeled 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotide ([ 68 Ga]DOTATOC) to determine a potential correlation between uptake in normal organs and NET burden., Procedures: Of the 44 included patients, 36/44 (82 %) patients demonstrated suspicious radiotracer uptake on [ 68 Ga] DOTATOC positron emission tomography (PET)/X-ray computed tomography (CT). Volumes of interest (VOIs) were defined for tumor lesions and normal organs (spleen, liver, kidneys, adrenals). Mean body weight corrected standardized uptake value (SUV mean ) for normal organs was assessed and was used to calculate the corresponding mean specific activity uptake (Upt: fraction of injected activity per kg of tissue). For the entire tumor burden, SUV mean , maximum standardized uptake value (SUV max ), and the total mass (TBM) was calculated and the decay corrected tumor fractional uptake (TBU) was assessed. A Spearman's rank correlation coefficient was used to determine the correlations between normal organ uptake and tumor burden., Results: The median SUV mean was 18.7 for the spleen (kidneys, 9.2; adrenals, 6.8; liver, 5.6). For tumor burden, the median values were SUV mean 6.9, SUV max 35.5, TBM 42.6 g, and TBU 1.2 %. With increasing volume of distribution, represented by lean body mass and body surface area (BSA), Upt decreased in kidneys, liver, and adrenal glands and SUV mean increased in the spleen. Correlation improved only for both kidneys and adrenals when the influence of the tumor uptake on the activity available for organ uptake was taken into account by the factor 1/(1-TBU). TBU was neither predictive for SUV mean nor for Upt in any of the organs. The distribution of organ Upt vs. BSA/(1-TBU) were not different for patients with minor TBU (<3 %) vs. higher TBU (>7 %), indicating that the correlations observed in the present study are explainable by the body size effect. High tumor mass and uptake mitigated against G1 NET., Conclusions: There is no significant impact on normal organ biodistribution with increasing tumor burden on [ 68 Ga] DOTATOC PET/CT. Potential implications include increased normal organ dose with [ 177 Lu-DOTA] 0 -D-Phe 1 -Tyr 3 -Octreotide and decreased absolute lesion detection with [ 68 Ga] DOTATOC in high NET burden.

Version 5 of the procedural guideline for Iodine-131 whole-body scintigraphy (WBS) in differentiated thyroid carcinoma is an update of the version 4, published by the "Deutsche Gesellschaft für Nuklearmedizin" (DGN). This procedural guideline advises on how to best perform I-131 whole body scintigraphy after I-131 therapy or after application of a diagnostic I-131 activity. A representative expert group has discussed and reached consensus on the procedural guideline; the development of this procedural guideline therefore fulfils the criteria for level S1 (first step) within the classification of the German Workgroup of Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften"; AWMF)., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aim: to evaluate the time trend of epidemiology of follicular cell derived thyroid cancer (TC) based on data from a well documented cancer registry., Methods: Population based data on TC from Lower Franconia (LF), Germany, within 1981 and 2015 were analysed to estimate the regional epidemiology of TC. The incidence was assessed in 5-year-intervals for gender, histology, and tumor stage., Results: Incidence of TC solely attributable to papillary TC (PTC) doubled mainly in T1- and T2-stages within the evaluation period from 4.5 to 8.7/100.000/y in females and 1.7 to 4.1/100.000/y in males. There was no significant change of follicular TC (FTC), whereas anaplastic TC (ATC) decreased in the same interval. The number of lymph-node metastases and T3-cases increased, while the frequency of T4-stage and distant metastases decreased. Increased incidences of T1- and T2-stages suggest an over-diagnosis. In contrast, increasing number of tumors at T3-stage and with lymph node involvement contradict the over-diagnosis as the only reason for rising incidence. Declining of T4-stages in spite of increasing of T3-stages and N1-cases indicates the value of timely detection and treatment of TC. In accordance, reduced incidence of advanced cancers with M1-stage and ATC cases promote our current management of TC., Conclusion: Timely diagnosis and adequate risk-adopted treatment of thyroid cancer reduce the frequency of high-risk cases with distant metastases and the possible protracted dedifferentiation of TC to anaplastic features. Our analyses support the management algorithm in thyroid cancer according to the recent guidelines of German Nuclear Medicine Society., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

We have recently reported on our experience with C-X-C-motif chemokine receptor 4 (CXCR4)-directed radioligand therapy (RLT) in multiple myeloma and acute leukemia. Methods: Six patients with heavily pretreated relapsed diffuse large B-cell lymphoma (3 men, 3 women; aged, 54 ± 8 y) underwent CXCR4-directed RLT in combination with conditioning chemotherapy and allogeneic stem cell transplantation. In 2 patients, radioimmunotherapy targeting CD20 or CD66 was added to enhance antilymphoma activity. Endpoints were incidence and severity of adverse events, progression-free survival, and overall survival. Results: RLT and additional radioimmunotherapy were well tolerated, without any acute adverse events or changes in vital signs. Successful engraftment was recorded after a median of 11 d (range, 9-13 d). Of the 4 patients who were available for follow-up (one patient died of CNS aspergillosis 29 d after RLT and another of sepsis in aplasia 34 d after RLT), CXCR4-directed RLT resulted in a partial response in two (both treated with additional radioimmunotherapy) and a mixed response in the remaining two. The response duration was rather short-lived, with a median progression-free survival of 62 d (range, 29-110 d) and a median overall survival of 76 d (range, 29-334 d). Conclusion: CXCR4-directed RLT (in combination with additional radioimmunotherapy) is feasible as a conditioning regimen before allogeneic stem cell transplantation in diffuse large B-cell lymphoma., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Aim: This work describes a small-scale production of iodine-124 using a 16.5 MeV cyclotron, and a subsequent validation of the formulated sodium [124I]iodide solution for routinely clinical applications., Methods: Iodine-124 ( 124 I) was produced via the 124 Te(p, n) 124 I reaction using a 16.5 MeV GE PETtrace® cyclotron. Irradiation was performed with a pre-prepared solid target consisting of [ 124 Te]TeO 2 (99.93%) and Al 2 O 3 . Different layer thicknesses, irradiation and extraction parameters were tested. After irradiation at the cyclotron, the shuttle with irradiated material was transferred fully automatically via a tube system to the Comecer ALCEO ® Halogen 2.0 extraction unit. Iodine-124 was subsequently extracted in form of sodium [ 124 I]iodide ([ 124 I]NaI) in 0.05 N aqueous NaOH solution, followed by reconstitution and validation for preclinical and clinical uses., Results: Good result was achieved using a beam degradation foil of 500 µm thickness in combination with beam currents between 10 and 15 µA. Under these conditions, up to 150 MBq no-carrier-added [ 124 I]NaI was obtained after a 2 h irradiation time in less than 500 µl 0.05 N NaOH. Isolation of [ 124 I]NaI, including evaporation and extraction at the ALCEO ® Halogen EVP unit was accomplished in 90 min 24 h after production (irradiation), the amount of iodine-123 as assessed by gamma-ray spectroscopy was less than 1.5%. The undesirable iodine-125 was not detectable by gamma spectroscopy. The extracted [ 124 I]NaI could be used directly for radiolabeling purposes, and after buffering with phosphate buffered saline (PBS) and sterile filtration for clinical applications., Conclusions: Through the optimized conditions for irradiation and extraction, iodine-124 was produced in good radiochemical yields and high radionuclide purity. The generated injectable [ 124 I]NaI solution was sterile, non-pyrogenic and ready for preclinical and clinical applications after a sterile filtration through a 0.22 µm membrane filter., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Version 4 of the procedural guideline for Iodine-131 whole-body scintigraphy (WBS) in differentiated thyroid carcinoma is an update of the version 3, which was published by the "Deutsche Gesellschaft für Nuklearmedizin" (DGN) and the "Deutsche Gesellschaft für Medizinische Physik" (DGMP) in 2007. This procedural guideline advises on how to best perform I-131 whole body scintigraphy after I-131 therapy or after application of a diagnostic I-131 activity. The updated relevant medical indications for I-131 whole body scintigraphy are given in this procedural guideline. Novel insights on the relationship bet¬ween activity and image quality were incorporated in the updated recommendations. A representative expert group has discussed and reached consensus on the procedural guideline; the development of this procedural guideline therefore fulfils the criteria for level S1 (first step) within the classification of the German Workgroup of Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften"; AWMF). Additionally, indications for WBS, timing and activity for WBS were discussed by the working group "Thyroid" of the DGN on November 30th 2012, April 19th, 2013 and on April 23rd, 2015., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Georg Thieme Verlag.)