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Absorbed radiation doses are essential in assessing the effects, e.g. safety and efficacy, of radiopharmaceutical therapy (RPT). Patient-specific absorbed dose calculations in the target or the organ at risk require multiple inputs. These include the number of disintegrations in the organ, i.e. the time-integrated activities (TIAs) of the organs, as well as other parameters describing the process of radiation energy deposition in the target tissue (i.e. mean energy per disintegration, radiation dose constants, etc). TIAs are then estimated by incorporating the area under the radiopharmaceutical's time-activity curve (TAC), which can be obtained by quantitative measurements of the biokinetics in the patient (typically based on imaging data such as planar scintigraphy, SPECT/CT, PET/CT, or blood and urine samples). The process of TAC determination/calculation for RPT generally depends on the user, e.g., the chosen number and schedule of measured time points, the selection of the fit function, the error model for the data and the fit algorithm. These decisions can strongly affect the final TIA values and thus the accuracy of calculated absorbed doses. Despite the high clinical importance of the TIA values, there is currently no consensus on processing time-activity data or even a clear understanding of the influence of uncertainties and variations in personalised RPT dosimetry related to user-dependent TAC calculation. As a first step towards minimising site-dependent variability in RPT dosimetry, this work provides an overview of quality assurance and uncertainty management considerations of the TIA estimation.

Introduction: The activity meter is used to determine the activity of delivered radiopharmaceuticals, administered activity to patients and reference activity when gamma-cameras are calibrated prior to imaged-based dosimetry. The aim is to describe a procedure for cross-calibration of activity meters at different clinical sites, and report on 177Lu activity results when using factory-set calibration factors compared to when calibration is performed with traceability to a primary standard. Methods: Thirty activity meters placed at seven hospitals in Norway and Sweden from four manufacturers: Capintec, Commecer, NuviaTech and Veenstra were included. A stock solution with 177Lu was prepared at the local sites and measured in each activity meter with factory settings. The solution was shipped to the reference site at Lund University for measurements in a secondary standard activity meter. Deviations between local and reference activity measurements were determined for three geometries: 25-mL vial, 10-mL syringe and 1-mL syringe. Results: The median of the deviations was 6.4 % for the 25 mL vial, 5.9 % for the 10 mL syringe and 6.8 % for the 1 mL syringe. The median of the deviations for the 25 mL vial, was 1.5 % for activity meters from Capintec, 7.0 % for Comecer, 11.0 % for NuviaTech and 2.4 % for Veenstra. The majority of the deviations were positive and the maximum deviation was 14.5 %. Conclusion: The activity of 177Lu measured in an activity meter with factory-set dial settings may yield deviations up to 14.5%, compared to activities measured with traceability to a primary standard. This would imply an undertreatment of patients.

Dosimetry can be a useful tool for personalization of molecular radiotherapy (MRT) procedures, enabling the continuous development of theranostic concepts. However, the additional resource requirements are often seen as a barrier to implementation. This guide discusses the requirements for dosimetry and demonstrates how a dosimetry regimen can be tailored to the available facilities of a centre. The aim is to help centres wishing to initiate a dosimetry service but may not have the experience or resources of some of the more established therapy and dosimetry centres. The multidisciplinary approach and different personnel requirements are discussed and key equipment reviewed example protocols demonstrating these factors are given in the supplementary material for the main therapies carried out in nuclear medicine, including [131I]-NaI for benign thyroid disorders, [177Lu]-DOTATATE and 131I-mIBG for neuroendocrine tumours and [90Y]-microspheres for unresectable hepatic carcinoma.

Dosimetry can be a useful tool for personalization of molecular radiotherapy (MRT) procedures, enabling the continuous development of theranostic concepts. However, the additional resource requirements are often seen as a barrier to implementation. This guide discusses the requirements for dosimetry and demonstrates how a dosimetry regimen can be tailored to the available facilities of a centre. The aim is to help centres wishing to initiate a dosimetry service but may not have the experience or resources of some of the more established therapy and dosimetry centres. The multidisciplinary approach and different personnel requirements are discussed and key equipment reviewed example protocols demonstrating these factors are given in the supplementary material for the main therapies carried out in nuclear medicine, including [131I]-NaI for benign thyroid disorders, [177Lu]-DOTATATE and 131I-mIBG for neuroendocrine tumours and [90Y]-microspheres for unresectable hepatic carcinoma.

Omkring 10% av befolkningen lider av defekt färgseende. De flesta, upptill 99%, av dessa är röd-grön färgblinda. Den sista procenten delasmellan totalt färgblinda och de med gul-blå färgblindhet. I studienidentifieras riktlinjer för hur färgsättning av diagram och kurvor ska görasför att även de med någon av de nämnda typerna av defekt färgseende skakunna tillgodogöra sig informationen i till exempel diagram. Baserat påteorier, samt egen personlig erfarenhet skapades bilder på färgsattakurvdiagram anpassade för personer med röd-grön färgblindhet. Dessahar testats och utvärderats av informanter som lever med den typen avdefekt färgseende. Detsamma gäller för skapandet av bilder för de medblå-gul färgblindhet. En färgsättning med enbart grundfärgerna gul, rödoch blå tillsammans med svart visade sig fungera för båda typerna avdefekt färgseende. Dessa färger tillsammans med svart mot en vitbakgrund ger inte bara ett tydligt intryck utan är också estetiskttilltalande.Genom att göra olika markeringar av linjerna i form av olika typer avsträckningar eller punkter, kan lätt fler än fyra kurvor finnas i sammadiagram. I studien presenteras möjliga färgkombinationer ochförklaringar kring varför de fungerar ihop. Detta bör vara tidsbesparandeoch kostnadseffektivt vid färgsättning av diagram likväl som webbsidoroch grafiska användargränssnitt mm. Informanternas tips och idéer på hurman ytterligare kan underlätta för de med defekt färgseende finns ocksåmed i rapporten., Approximately 10% of the population suffer from defective color vision. Up to 99%of these persons suffer from red-green defective color vision. The last percentage isshared between those that are totally colorblind and those suffering from yellow-bluecolor defective color vison. This study identifies how correct use of colors will makesure that people suffering from any of the above-mentioned types of defective colorvision conditions will be able to assimilate the information given in, for example, adiagram. Based on theories, as well as personal experience, images were created oncolored curve diagrams adapted for people with red-green color blindness. These havebeen tested and evaluated by informants living with that type of defective colorvision. The same applies when it comes to the creation of the pictures for thosesuffering from blue-yellow defective color vision.A color scheme using only the primary colors yellow, red and blue together withblack proved to work for both types of defective color vision. These colors togetherwith black on a white background not only give a clear impression but are alsoaesthetically appealing. By making different markings of the lines in the form ofdashed lines or dots, more than four curves can easily be found in the same diagram.The study presents possible combinations of colors and explanations to why theywork together. This should be time saving and cost effective when coloring diagrams and also when for example coloring webpages and graphical user interfaces. The tipsand ideas given by the informants how to further facilitate for the persons sufferingfrom defective color vision is also found in the report.

Radionuclide molecular imaging of human epidermal growth factor (HER2) expression may be helpful to stratify breast and gastroesophageal cancer patients for HER2-targeting therapies. ADAPTs (albumin-binding domain derived affinity proteins) are a new type of small (46-59 amino acids) proteins useful as probes for molecular imaging. The aim of this first-in-human study was to evaluate biodistribution, dosimetry, and safety of the HER2-specific 99mTc-ADAPT6. METHODS: Twenty-nine patients with primary breast cancerwere included. In 22 patients with HER2-positive (n = 11) or HER2-negative (n = 11) histopathology an intravenous injection with 385±125 MBq 99mTc-ADAPT6 was performed, randomized to an injected protein mass of either 500 µg (n = 11) or 1000 µg (n = 11). Planar scintigraphy followed by SPECT imaging was performed after 2, 4, 6 and 24 h. An additional cohort (n = 7) was injected with 165±29 MBq (injected protein mass 250 µg) and imaging was performed after 2 h only. RESULTS: Injections of 99mTc-ADAPT6 at all injected mass levels were well tolerated and not associated with adverse effects. 99mTc-ADAPT6 cleared rapidly from blood and most other tissues. The normal organs with the highest accumulation were kidney, liver and lung. Effective doses were 0.009±0.002 and 0.010±0.003 mSv/MBq for injected protein masses of 500 and 1000 µg, respectively. Injection of 500 µg resulted in excellent discrimination between HER2-positive and HER2-negative tumors already 2 h after injection (tumor-to-contralateral breast ratio was 37±19 vs 5±2, p<0.01). The tumor-to-contralateral breast ratios for HER2-positive tumors were significantly (p<0.05) higher for injected mass of 500 µg than for both 250 and 1000 µg. CONCLUSION: Injections of 99mTc-ADAPT6 are safe and associated with low absorbed and effective doses. Protein dose of 500 µg is preferable for discrimination between tumors with high and low expression of HER2. Further studies are justified to evaluate if 99mTc-ADAP

Dosimetry during peptide receptor radionuclide therapy (PRRT) has mainly focused on normal organs and less on the tumors. The absorbed dose in one target tumor per patient and several response related factors were assessed in 23 pancreatic neuroendocrine neoplasms (P-NENs) and 25 small-intestinal NEN (SI-NENs) during PRRT with 177Lu-DOTATATE. The total administered activity per patient was (mean ± standard error of mean (SEM) 31.8 ± 1.9 GBq for P-NENs and 36 ± 1.94 GBq for SI-NENs. The absorbed tumor dose was 143.5 ± 2 Gy in P-NENs, 168.2 ± 2 Gy in SI-NENs. For both NEN types, a dose-response relationship was found between the absorbed dose and tumor shrinkage, which was more pronounced in P-NENs. A significant drop in the absorbed dose per cycle was shown during the course of PRRT. Tumor vascularization was higher in P-NENs than in SI-NENs at baseline but equal post-PRRT. The time to progression (RECIST 1.1) was similar for patients with P-NEN (mean ± SEM 30 ± 1 months) and SI-NEN (33 ± 1 months). In conclusion, a dose response relationship was established for both P-NENs and SI-NENs and a significant drop in the absorbed dose per cycle was shown during the course of PRRT, which warrants further investigation to understand the factors impacting PRRT to improve personalized treatment protocol design.

Peptide receptor radiotherapy using 177Lu-labeled somatostatin ligand analogs is a well-established treatment for neuroendocrine tumors, with 177Lu-DOTATATE having acquired marketing authorization in Europe and the United States. The investigation of the pharmacokinetics of these radiopharmaceuticals in vivo in humans is crucial for personalized treatment management and understanding of treatment effects. Such an investigation requires input data on the in vivo stability of the radiopharmaceuticals in blood and plasma. The work presented here is devoted to the investigation of the in vivo stability of 177Lu-DOTATATE in humans affected by neuroendocrine tumors. Methods: Blood samples of 6 patients undergoing 177Lu-DOTATATE were taken at 0.5, 4, 24, and 96 h after injection. Analysis of metabolic stability was performed using high-performance liquid chromatography. Results: A fast metabolism of the radiopharmaceutical was observed, with the fraction of intact 177Lu-DOTATATE in plasma decreasing rapidly to 23% ± 5% (mean ± SD) at 24 h and 1.7% ±0. 9% at 96 h after injection. Conclusion: The in vivo stability of 177Lu-DOTATATE is much lower than previously assumed, with the major part of radioactivity in plasma consisting of 177Lu-labeled metabolites already at 24 h after injection.

Introduction: Peptide receptor radionuclide therapy (PRRT) has during the last few years been frequently used in patients with progressive, disseminating, well-differentiated neuroendocrine tumors (NETs). Objective: To study whether the absorbed dose in small intestinal NET (SI-NET) metastases from PRRT with 177Lu-DOTATATE is related to tumor shrinkage. Materials and Methods: Dosimetry for 1 tumor was performed in each of 25 SI-NET patients based on sequential SPECT/CT 1, 4, and 7 days after 177Lu-DOTATATE infusion. The SPECT data were corrected for the partial volume effect based on previous phantom measurements, and the unit density sphere model from OLINDA was used for absorbed dose calculations. Morphological therapy response was assessed by CT/MRI regarding tumor diameter, tumor volume, total liver tumor volume, liver volume, and overall tumor response according to RECIST 1.1. Plasma chromogranin A and urinary 5-hydroxy-indole-acetic-acid were measured during PRRT and follow-up to assess biochemical response. Results: At the time of best response with respect to tumor diameter and volume shrinkage, the median absorbed dose was 128.6 Gy (range 28.4–326.9) and 140 Gy (range 50.9–487.4), respectively. All metrics regarding tumor shrinkage and biochemical response were unrelated to the absorbed dose. A correlation was, however, found between the administered radioactivity and the tumor volume shrinkage (p = 0.01) and between the administered radioactivity and RECIST 1.1 response (p = 0.01). Conclusions: It was not possible to demonstrate a tumor dose-response relationship in SI-NET metastases with the applied dosimetry method, contrary to what was previously shown for pancreatic NETs., De två första författarna delar förstaförfattarskapet

PET/CT with 68Ga-DOTA-somatostatin analogs has been tested for therapy monitoring in patients with neuroendocrine tumors (NETs). However, standardized uptake values (SUV) in tumors do not correlate with the net influx rate (Ki), as a representation of the somatostatin receptor (SSTR) expression. In this study, tumor-to-blood-ratio (TBR) was evaluated as an alternative tool for semi-quantitative assessment of 68Ga-DOTATOC and 68Ga-DOTATATE tumor uptake and as a therapy monitoring tool for patients with NETs. Methods: Twenty-two NET patients underwent a 45-min dynamic PET/CT scan after injection of 68Ga-DOTATOC and/or 68Ga-DOTATATE. Ki was determined using the Patlak method and TBR was calculated for the 40-45 min time interval. Results: A linear relation was found between Ki and TBR, with a square of Pearson correlation (R2) of 0.98 and 0.93 for 68Ga-DOTATOC and 68Ga-DOTATATE, respectively. Conclusion: High correlation was found between Ki and TBR. Hence, TBR reflects SSTR density more accurately than SUV and is suggested as the preferred metrics for semi-quantitative assessment of 68Ga-DOTATOC and 68Ga-DOTATATE tumor uptake.