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Executive SummaryThe EC Directive 2013/59/Euratom states in article 56 that exposures of target volumes in nuclear medicine treatments shall be individually planned and their delivery appropriately verified. The Directive also mentions that medical physics experts should always be appropriately involved in those treatments. Although it is obvious that, in nuclear medicine practice, every nuclear medicine physician and physicist should follow national rules and legislation, the EANM considered it necessary to provide guidance on how to interpret the Directive statements for nuclear medicine treatments.For this purpose, the EANM proposes to distinguish three levels in compliance to the optimization principle in the directive, inspired by the indication of levels in prescribing, recording and reporting of absorbed doses after radiotherapy defined by the International Commission on Radiation Units and Measurements (ICRU): Most nuclear medicine treatments currently applied in Europe are standardized. The minimum requirement for those treatments is ICRU level 1 (“activity-based prescription and patient-averaged dosimetry”), which is defined by administering the activity within 10% of the intended activity, typically according to the package insert or to the respective EANM guidelines, followed by verification of the therapy delivery, if applicable.Non-standardized treatments are essentially those in developmental phase or approved radiopharmaceuticals being used off-label with significantly (> 25% more than in the label) higher activities. These treatments should comply with ICRU level 2 (“activity-based prescription and patient-specific dosimetry”), which implies recording and reporting of the absorbed dose to organs at risk and optionally the absorbed dose to treatment regions.The EANM strongly encourages to foster research that eventually leads to treatment planning according to ICRU level 3 (“dosimetry-guided patient-specific prescription and verification”), whenever possible and relevant.Evidence for superiority of therapy prescription on basis of patient-specific dosimetry has not been obtained. However, the authors believe that a better understanding of therapy dosimetry, i.e. how much and where the energy is delivered, and radiobiology, i.e. radiation-related processes in tissues, are keys to the long-term improvement of our treatments.

Background 18 F -fluorodeoxyglucose (FDG) positron emission tomography (PET) plays an important role in the staging and response assessment of lymphoma patients. Our aim was to explore the predictive relevance of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in patients with early stage Hodgkin lymphoma treated within the German Hodgkin Study Group HD16 trial. Methods 18 F-FDG PET/CT images were available for MTV and TLG analysis in 107 cases from the HD16 trial. We calculated MTV and TLG using three different threshold methods (SUV 4.0, SUV 41% and SUV 140%L ), and then performed receiver-operating-characteristic analysis to assess the predictive impact of these parameters in predicting an adequate therapy response with PET negativity after 2 cycles of chemotherapy. Results All three threshold methods analyzed for MTV and TLG calculation showed a positive correlation with the PET response after 2 cycles chemotherapy. The largest area under the curve (AUC) was observed using the fixed threshold of SUV 4.0 for MTV- calculation (AUC 0.69 [95% CI 0.55–0.83]) and for TLG-calculation (AUC 0.69 [0.55–0.82]). The calculations for MTV and TLG with a relative threshold showed a lower AUC: using SUV 140%L AUCs of 0.66 [0.53–0.80] for MTV and 0.67 for TLG [0.54–0.81]) were observed, while with SUV 41% an AUC of 0.61 [0.45–0.76] for MTV, and an AUC 0.64 [0.49–0.80]) for TLG were seen. Conclusions MTV and TLG do have a predictive value after two cycles ABVD in early stage Hodgkin lymphoma, particularly when using the fixed threshold of SUV 4.0 for MTV and TLG calculation. Trial registration ClinicalTrials.gov NCT00736320 .

Since the mid-1990s, 18F-fluorodeoxglucose (FDG)-positron emission tomography (PET) in combination with computed tomography has come to play a prominent role in the management of malignant lymphomas. One of the first PET applications in oncology was the detection of lymphoma manifestations at staging, where it has shown high sensitivity. Nowadays, this imaging modality is also used during treatment to evaluate the individual chemosensitivity and adapt further therapy accordingly. If the end-of-treatment PET is negative, irradiation in advanced-stage Hodgkin lymphoma patients can be safely omitted after highly effective chemotherapy. Thus far, lymphoma response assessment has mainly been performed using visual criteria, such as the Deauville five-point scale, which became the international standard in 2014. However, novel measures such as metabolic tumor volume or total lesion glycolysis have recently been recognized by several working groups and may further increase the diagnostic and prognostic value of FDG-PET in the future.

BackgroundIn 2022, the American Food and Drug Administration and the European Medicines Agency approved [177Lu]Lu-PSMA-617 (PLUVICTO™, Novartis AG, Basel, Switzerland) for radionuclide therapy with prostate-specific membrane antigen (PSMA) ligands in metastatic prostate cancer. Theranostics require appropriate patients to be identified by positron emission tomography (PET) prior to radionuclide therapy, usually employing [68Ga]Ga-PSMA-11. Alternatively, several 18F-labelled PSMA-PET tracers are available and may increasingly replace 68Ga-labelled compounds, with respect to their image quality, availability and other practical advantages. However, alternative tracers may differ in uptake behaviour, and their comparability with regard to patient selection for [177Lu]Lu-PSMA therapy has not yet been established. Here, we analysed whether tumour-to-background ratios determined by PET using the 18F-labelled PSMA-specific radiopharmaceutical [18F]F-DCFPyL were comparable to those determined by PET using [68Ga]Ga-PSMA-11.ResultsNo differences could be observed between [68Ga]Ga-PSMA-11-PET and [18F]F-DCFPyL-PET regarding tumour-to-liver ratios or tumour-to-mediastinum ratios (e. g. tumour-to-liver ratios using maximum SUV of the tumour lesion for ultra-high definition reconstructed PET images with a median of 2.5 (0.6–9.0) on [68Ga]Ga-PSMA-11-PET vs. 2,0 (0.6–11.4) on [18F]F-DCFPyL-PET). However, significant differences were observed in terms of contrast-to-noise ratios, thereby demonstrating the better image quality obtained with [18F]F-DCFPyL-PET.ConclusionsOur data showed that [18F]F-DCFPyl-PET and [68Ga]Ga-PSMA-11-PET provide comparable tumour-to-liver and tumour-to-mediastinum ratios. Therefore, a tumour uptake of [18F]F-DCFPyL above the liver background, like using [68Ga]Ga-PSMA-11, can be considered as equally suitable for defining PSMA-positivity by a semiquantitative assessment based on the liver background, e. g. prior to radioligand therapy with 177Lu-labelled PSMA ligands. In addition, our data suggest a tending advantage of [18F]F-DCFPyL in terms of lesion detectability.

Background Fibroblast activation protein (FAP) is expressed in the tumor microenvironment (TME) of various cancers. In our analysis, we describe the impact of dual-tracer imaging with Gallium-68-radiolabeled inhibitors of FAP (FAPI-46-PET/CT) and fluorodeoxy-D-glucose (FDG-PET/CT) on the radiotherapeutic management of primary esophageal cancer (EC). Methods 32 patients with EC, who are scheduled for chemoradiation, received FDG and FAPI-46 PET/CT on the same day (dual-tracer protocol, 71%) or on two separate days (29%) We compared functional tumor volumes (FTVs), gross tumor volumes (GTVs) and tumor stages before and after PET-imaging. Changes in treatment were categorized as “minor” (adaption of radiation field) or “major” (change of treatment regimen). Immunohistochemistry (IHC) staining for FAP was performed in all patients with available tissue. Results Primary tumor was detected in all FAPI-46/dual-tracer scans and in 30/32 (93%) of FDG scans. Compared to the initial staging CT scan, 12/32 patients (38%) were upstaged in nodal status after the combination of FDG and FAPI-46 PET scans. Two lymph node metastases were only visible in FAPI-46/dual-tracer. New distant metastasis was observed in 2/32 (6%) patients following FAPI-4 -PET/CT. Our findings led to larger RT fields (“minor change”) in 5/32 patients (16%) and changed treatment regimen (“major change”) in 3/32 patients after FAPI-46/dual-tracer PET/CT. GTVs were larger in FAPI-46/dual-tracer scans compared to FDG-PET/CT (mean 99.0 vs. 80.3 ml, respectively ( p  < 0.001)) with similar results for nuclear medical FTVs. IHC revealed heterogenous FAP-expression in all specimens (mean H-score: 36.3 (SD 24.6)) without correlation between FAP expression in IHC and FAPI tracer uptake in PET/CT. Conclusion We report first data on the use of PET with FAPI-46 for patients with EC, who are scheduled to receive RT. Tumor uptake was high and not depending on FAP expression in TME. Further, FAPI-46/dual-tracer PET had relevant impact on management in this setting. Our data calls for prospective evaluation of FAPI-46/dual-tracer PET to improve clinical outcomes of EC.

[68Ga]PSMA-HBED-CC and [18F]DCFPyL show a high potential for the detection of recurrent prostate cancer. While 18F-based tracers have several advantages in availability and image resolution, their sensitivity in the skeleton might be impaired by released [18F]fluoride due to its high bone affinity. In turn, chemically unbound trivalent 68Ga might also accumulate in osseous tissue, in cases of occupied binding sites of plasma proteins and thereby influence bone signal. A comparison of average bone SUV was performed in 17 bone-negative and 4 bone-positive patients. All patients underwent PET/CT 125 minutes after application of [18F]DCFPyL and 73 minutes after application of [68Ga]PSMA-HBED-CC at another date. Native SUVs in unaffected bone tissue and SUVs relative to liver uptake were lower in [18F]DCFPyL (0.49) than in [68Ga]PSMA-HBED-CC scans (0.52). SUVs relative to gluteal muscles did not differ between the two tracers. Average lesional SUVs did not differ between tracers. No difference of average bone signal intensity was observed for [18F]DCFPyL-PET/CT in comparison to [68Ga]PSMA-HBED-CC scans indicating that diagnostic assessment of the skeleton is not affected by non-specific accumulation of free [18F]fluoride or 68Ga.

Various factors have been identified that influence quantitative accuracy and image interpretation in positron emission tomography (PET). Through the continuous introduction of new PET technology—both imaging hardware and reconstruction software—into clinical care, we now find ourselves in a transition period in which traditional and new technologies coexist. The effects on the clinical value of PET imaging and its interpretation in routine clinical practice require careful reevaluation. In this review, we provide a comprehensive summary of important factors influencing quantification and interpretation with a focus on recent developments in PET technology. Finally, we discuss the relationship between quantitative accuracy and subjective image interpretation.

The five point Deauville (D) scale is widely used to assess interim PET metabolic response to chemotherapy in Hodgkin lymphoma (HL) patients. An International Validation Study reported good concordance among reviewers in ABVD treated advanced stage HL patients for the binary discrimination between score D1,2,3 and score D4,5. Inter-reader reliability of the whole scale is not well characterised. Five international expert readers scored 100 interim PET/CT scans from paediatric HL patients. Scans were acquired in 51 European hospitals after two courses of OEPA chemotherapy (according to the EuroNet-PHL-C1 study). Images were interpreted in direct comparison with staging PET/CTs. The probability that two random readers concord on the five point D score of a random case is only 42% (global kappa = 0.24). Aggregating to a three point scale D1,2 vs. D3 vs. D4,5 improves concordance to 60% (kappa = 0.34). Concordance if one of two readers assigns a given score is 70% for score D1,2 only 36% for score D3 and 64% for D4,5. Concordance for the binary decisions D1,2 vs. D3,4,5 is 67% and 86% for D1,2,3 vs D4,5 (kappa = 0.36 resp. 0.56). If one reader assigns D1,2,3 concordance probability is 92%, but only 64% if D4,5 is called. Discrepancies occur mainly in mediastinum, neck and skeleton. Inter-reader reliability of the five point D-scale is poor in this interobserver analysis of paediatric patients who underwent OEPA. Inter-reader variability is maximal in cases assigned to D2 or D3. The binary distinction D1,2,3 versus D4,5 is the most reliable criterion for clinical decision making.