We evaluated the diagnostic performance of fibroblast activation protein inhibitor (FAPI) PET for lesion detection at breast cancer diagnosis and response assessment after neoadjuvant chemoimmunotherapy (NAC) and compared these findings with those from [18F]FDG PET or histopathology after the completion of NAC. Methods: A systematic search across PubMed, EMBASE, Web of Science, and Cochrane Trial databases up to January 12, 2026, was conducted. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies version 2 tool. Extracted data included SUVmax, tumor-to-background ratio, and lesion detection in studies comparing FAPI PET with [18F]FDG PET. For studies comparing FAPI PET with histopathology, diagnostic performance parameters were obtained. Data on FAPI uptake, stratified by histology type, molecular subtype, and tumor grade, were extracted. Results: The literature search yielded 3662 studies, 13 of which were included in this review. Of these, 10 compared FAPI PET with [18F]FDG PET and 3 compared FAPI PET findings with those of histopathology after the completion of NAC. The reported mean SUVmax range was 6.5-17.1 versus 3.9-8.3 for primary tumors, 5.1-17.1 versus 1.2-10.3 for axillary lymph node metastases, and 4.9-21.7 versus 1.7-8.1 for distant metastases on FAPI PET versus [18F]FDG PET, respectively. FAPI PET detected more lesions compared with [18F]FDG PET in all evaluated anatomic sites. In post-NAC response assessment of the breast tumor, FAPI PET reported a sensitivity and specificity of 73%-100% and 71%-100%, respectively. Lower FAPI uptake was observed in low-grade, luminal A tumors and in those with lobular histology. Conclusion: FAPI PET demonstrated increased lesion detection compared with [18F]FDG PET at the time of breast cancer diagnosis and demonstrated considerable diagnostic performance for assessing response evaluation after NAC.

As the main inhibitory neurotransmission system, the GABAergic system poses an interesting yet underutilized target for molecular brain imaging. While PET imaging of postsynaptic GABAergic neurons has been accomplished using radiolabeled benzodiazepines targeting the GABAA receptor, the development of presynaptic radioligands targeting GABA transporter 1 (GAT1) has been unsuccessful thus far. Therefore, we developed a novel GAT1-addressing radioligand and investigated its applicability as a PET tracer in rodents. We selected a lipophilic nipecotic acid scaffold that is known to bind selectively to GAT1 as the basis for our radioligand. To obtain the desired candidate radiotracer [ 18 F]4, ester-protected radioligands [ 18 F]11a-b were synthesized through aliphatic nucleophilic radiofluorination of the respective bromo-precursors, after which chemical deprotection was attempted using various conditions. Because these deprotections were unsuccessful, it was evaluated whether the ethyl ester [ 18 F]11a could function as a prodrug and afford the active radioligand [ 18 F]4 after in vivo ester hydrolysis by esterases. Unfortunately, PET imaging studies in a rat model using [ 18 F]11a showed no brain uptake of the radiotracer. Instead, significant uptake of radioactivity was observed in the liver and bones, the latter being caused by radiodefluorination of the PET tracer. Since the PET tracer developed in this study was found to be unstable, further efforts should investigate the development of a more stable GAT1-addressing PET tracer without the potential labile benzyl fluoride moiety. Moreover, as the still intact fraction of the radiotracer did not cross the BBB, options other than the prodrug approach should be considered to increase the BBB permeability of future GAT1 radioligands.

In this study, we investigated the utility of a novel developed anti-CEACAM5 VHH for cancer diagnosis and its potential of being a targeting-moiety of VHH-drug conjugates for cancer therapy. Anti-CEACAM5 VHH (6B11) affinity and specific cellular binding was confirmed by ELISA, FACS and immunofluorescence in cancer cell lines with varying CEACAM5 expression levels. Intracellular penetration ability within tumor spheroids was tested with Oregon Green 488 labeled 6B11 (OG488-6B11). Biodistribution and binding specificity of 99mTc-radiolabeled 6B11 was tested in A549 CEACAM5 overexpressing (A549-CEA5-OV) and knockout (A549-CEA5-KO) tumor-bearing mice upon SPECT/CT imaging, γ-counting and autoradiography. The therapeutic efficacy of 6B11 and 6F8 (anti-CEACAM5 VHH with lower binding affinity) was tested by viability, wound healing and adhesion assays. To verify the potential of VHHs as a warhead for VHH-drug conjugation, an internalization assay with OG488 labeled VHH was performed. 6B11 demonstrated high binding affinity (EC50 0.5nM) and cellular binding. OG488-6B11 penetrated tumor spheroids completely at 24 h, while a conventional antibody was only visible at the spheroid periphery. SPECT imaging indicated higher uptake (p < 0.05) in A549-CEA5-OV tumors, resulting in increased tumor-to-blood ratios especially at 4 (2.0016 ± 1.1893, p = 0.035) and 24 (2.9371 ± 2.0683, p = 0.003) hpi compared to A549-CEA5-KO tumors at 4 (0.5640 ± 0.3576) and 24 (0.8051 ± 0.4351) hpi. 99mTc-6B11 was predominantly renally cleared. Autoradiography and immunohistochemistry confirmed these uptake patterns. 6B11 nor 6F8 did exhibit significant anti-cancer therapeutic efficacy in vitro. OG488-6B11 was effectively internalized and accumulated in cells in a time-dependent manner, to end up in the lysosomes. The anti-CEACAM5 VHH 6B11 is a good candidate for SPECT-based cancer diagnosis and can be potentially used as targeting moiety in the development of VHH-based drug conjugates for cancer treatments.

BackgroundSince 2011, the International Commission on Radiological Protection (ICRP) has recommended an annual eye lens dose limit of 20 mSv for radiation workers, averaged over 5 years, with no year exceeding 50 mSv. However, limited research has been conducted on dose rate conversion coefficients (DCCs) for direct contamination of the eye.PurposeThis study aimed to accurately determine DCCs for the eye lens and cornea for ocular contamination with radionuclides used in nuclear medicine.MethodsDCCs for 37 radionuclides used in nuclear medicine were determined using two different methods. Method 1 involved conducting Monte Carlo (MC) simulations of an ICRU cylinder to determine the absorbed dose at a depth of 3 mm resulting from a point source. The accuracy of this simulation approach was validated by experimental thermoluminescent dosimeter (TLD) measurements for 18F, 68Ga, 99mTc, and 177Lu. In method 2, average DCCs were calculated for the eye lens (complete and radiosensitive parts) and the cornea for both a point source and thin surface contamination centered on the cornea using MC simulations on the adult mesh-type reference computational phantom of the eye from the ICRP (MRCP).ResultsDCCs determined from TLD measurements showed excellent agreement (deviations: +1.4%, +4.7%, -3.1%, and -2.5% for 18F, 68Ga, 99mTc, and 177Lu, respectively) compared to MC simulations of the experimental set-up. For the 37 radionuclides, DCCs of the complete eye-lens for a point source ranged from 2.53 x 10-7 to 4.15 x 10-2 mGy MBq-1 s-1 for the adult MRCPs, being substantially smaller compared to DCCs determined via MC simulations of a ICRU cylinder. In general, point source and surface contamination showed comparable DCCs for the eye lens. Radionuclides emitting low-energy beta radiation or conversion electrons (e.g., 177Lu, 99mTc) showed low DCCs as the radiation does not penetrate to the depth of the eye lens, while radionuclides emitting high-energy beta radiation (e.g., 90Y) showed high DCCs. Overall, DCCs for the radiosensitive part of the eye lens were larger (up to a factor of 3) compared to the complete eye lens. DCCs for the cornea were larger than for the eye lens with a factor that strongly depended on the emitted radiation type. Especially alpha emitters (e.g., 211At, 223Ra) showed high DCCs for the cornea because of the short range of alpha radiation, leading to local maxima in the cornea and not reaching the eye lens.ConclusionDCCs at a depth of 3 mm in an ICRU cylinder and adult MRCP DCCs for both the complete and sensitive parts of the eye lens and cornea were determined for 37 radionuclides having applications in nuclear medicine. These DCCs are highly useful in radiation safety assessments and radiation dose calculations in ocular contamination incidents.

Small animal Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) imaging techniques are crucial in preclinical cancer research, necessitating meticulous attention to radiotracer synthesis, quality assurance, and in vivo injection protocols. This study presents a comprehensive workflow tailored to enhance the robustness and reproducibility of small animal PET experiments. The synthesis process in the radiochemistry laboratory using 68 Ga is detailed, highlighting stringent quality control and assurance protocols for each radiotracer production. Parameters such as concentration, molar activity, pH, and purity are rigorously monitored, aligning with standards applicable to human studies. This methodology introduces streamlined syringe preparation and a custom- designed 30G cannula for precise intravenous injections into mice. Monitoring of animal health during scanning, including temperature and heart rate, ensures their well-being throughout the procedure. Dosages for PET and SPECT scans are predetermined to balance data acquisition with minimizing radiation exposure to animals and researchers. Similarly, CT scans employ pre-programmed settings to limit radiation exposure, especially pertinent in long-term studies assessing treatment effects. By optimizing these steps, the workflow aims to standardize procedures, reduce variability, and enhance the quality of small animal PET/SPECT/CT imaging. This resource provides valuable insights for researchers seeking to improve the accuracy and reliability of preclinical investigations in molecular imaging, ultimately advancing the field.

The authors wish to replace the ‘Author Contributions’ statement and the affiliation for Jochen Maurer of this article [...]

Background Triple-negative breast cancer (TNBC) lacks biomarkers for targeted therapy. Auger emitters display the best therapeutic effect, if delivered directly into the nucleus proximal to DNA. The nuclear protein Poly (ADP-ribose)-Polymerase 1 (PARP1) is a suitable target against which few inhibitors (PARPi) are clinically approved for treatment of breast cancer with germline BRCA mutation (BRCA mut ). In this study, a theranostic approach was investigated in a TNBC xenografted mouse model by radiolabelling a close derivative of a PARPi Olaparib (termed PARPi-01) with the Auger emitters 123/125 I. Methods TNBC cell line MDA-MB-231 was subcutaneously implanted in female NOD/SCID mice. At a tumour size of ~ 500mm 3 , [ 123 I]PARPi-01 was administered intravenously, and SPECT/CT images were obtained at 4 h or 24 h post injection (p.i). A therapy study was performed with [ 125 I]PARPi-01 in 4 doses (10 MBq/dose, 10 days apart). Tumour growth was monitored by CT scans longitudinally once per week. Upon reaching study endpoint, tissues were harvested and stained with TUNEL assay for detection of apoptosis induction. Results SPECT/CT images showed rapid hepatobiliary tracer clearance at 4 h post injection (p.i.). Retention in thyroid at 24 h p.i. suggested tracer deiodination in vivo. The tumour and liver uptake were 0.2%ID/g and 2.5%ID/g, respectively. The tumour: blood ratio was 1.3. Endogenous therapy induced a significant delay in tumour growth (doubling time increased from 8.3 to 14.2 days), but no significant survival advantage. Significantly higher apoptosis ratio was observed in [ 125 I]PARPi-01 treated tumour tissues. No radiotoxicity was detected in the liver and thyroid. Conclusion Considering the radio-cytotoxic effect in the tumour tissue and a delay on tumour doubling time, [ 125 I]PARPi-01 presents a potential radiotherapeutics for treatment of TNBC. Improvements to overcome the suboptimal pharmacokinetics are necessary for its potential clinical application.

By clearing GABA from the synaptic cleft, GABA transporters (GATs) play an essential role in inhibitory neurotransmission. Consequently, in vivo visualization of GATs can be a valuable diagnostic tool and biomarker for various psychiatric and neurological disorders. Not surprisingly, in recent years several research attempts to develop a radioligand have been conducted, but so far none have led to suitable radioligands that allow imaging of GATs. Here, we provide an overview of the radioligands that were developed with a focus on GAT1, since this is the most abundant transporter and most of the research concerns this GAT subtype. Initially, we focus on the field of GAT1 inhibitors, after which we discuss the development of GAT1 radioligands based on these inhibitors. We hypothesize that the radioligands developed so far have been unsuccessful due to the zwitterionic nature of their nipecotic acid moiety. To overcome this problem, the use of non-classical GAT inhibitors as basis for GAT1 radioligands or the use of carboxylic acid bioisosteres may be considered. As the latter structural modification has already been used in the field of GAT1 inhibitors, this option seems particularly viable and could lead to the development of more successful GAT1 radioligands in the future.

PARP1 inhibitors (PARPi) are currently approved for BRCAmut metastatic breast cancer, but they have shown limited response in triple negative breast cancer (TNBC) patients. Combination of an Auger emitter with PARPis enables PARP inhibition and DNA strand break induction simultaneously. This will enhance cytotoxicity and additionally allow a theranostic approach. This study presents the radiosynthesis of the Auger emitter [125I] coupled olaparib derivative: [125I]-PARPi-01, and its therapeutic evaluation in a panel of TNBC cell lines. Specificity was tested by a blocking assay. DNA strand break induction was analysed by γH2AX immunofluorescence staining. Cell cycle analysis and apoptosis assays were studied using flow cytometry in TNBC cell lines (BRCAwt/mut). Anchorage independent growth potential was evaluated using soft agar assay. [125I]-PARPi-01 showed PARP1-specificity and higher cytotoxicity than olaparib in TNBC cell lines irrespective of BRCA their status. Cell lines harbouring DNA repair deficiency showed response to [125I]-PARPi-01 monotherapy. Combined treatment with Dox-NP further enhanced therapeutic efficiency in metastatic resistant BRCAwt cell lines. The clonogenic survival was significantly reduced after treatment with [125I]-PARPi-01 in all TNBC lines investigated. Therapeutic efficacy was further enhanced after combined treatment with chemotherapeutics. [125I]-PARPi-01 is a promising radiotherapeutic agent for low radiation dosages, and mono/combined therapies of TNBC.

Although anatomical imaging modalities (X-ray, computed tomography (CT), magnetic resonance imaging (MRI)) still have a higher spatial resolution (0.1–1 mm) than molecular imaging modalities (single-photon emission computed tomography (SPECT), positron emission tomography (PET), optical imaging (OI)), the advantage of molecular imaging is that it can detect molecular and cellular changes at the onset of a disease before it leads to morphological tissue changes, which can be detected by anatomical imaging. During the last decades, noninvasive diagnostic imaging has encountered a rapid growth due to the development of dedicated imaging equipment for preclinical animal studies. In addition, the introduction of multimodality imaging (PET/CT, SPECT/CT, PET/MRI) which combines high-resolution conventional anatomical imaging with high sensitivity of tracer-based molecular imaging techniques has led to successful accomplishments in this exciting field. In this book chapter, we will focus on chemical synthesis techniques for site-specific incorporation of radionuclide chelators. Subsequently, radiolabeling based on complexation of a radionuclide with a chelator will be discussed, with focus on: diethylenetriaminepentaacetic acid (DTPA), 1,4,7,10-tetraazacyclododecane-tetraacetic acid (DOTA), 1,4,7-triazacyclononane-triacetic acid (NOTA), hexa-histidine (His-tag), and 6-hydrazinonicotinic acid (HYNIC) that allow the production of peptides labeled with 18F, 68Ga, 99mTc, and 111In – the currently most widely used isotopes.

Angiogenesis is an active process, regulating new vessel growth, and is crucial for the survival and growth of tumours next to other complex factors in the tumour microenvironment. We present possible molecular imaging approaches for tumour vascularisation and vitality, focusing on radiopharmaceuticals (tracers). Molecular imaging in general has become an integrated part of cancer therapy, by bringing relevant insights on tumour angiogenic status. After a structured PubMed search, the resulting publication list was screened for oncology related publications in animals and humans, disregarding any cardiovascular findings. The tracers identified can be subdivided into direct targeting of angiogenesis (i.e., vascular endothelial growth factor, laminin, and fibronectin) and indirect targeting (i.e., glucose metabolism, hypoxia, and matrix metallo-proteases, PSMA). Presenting pre-clinical and clinical data of most tracers proposed in the literature, the indirect targeting agents are not 1:1 correlated with angiogenesis factors but do have a strong prognostic power in a clinical setting, while direct targeting agents show most potential and specificity for assessing tumour vascularisation and vitality. Within the direct agents, the combination of multiple targeting tracers into one agent (multimers) seems most promising. This review demonstrates the present clinical applicability of indirect agents, but also the need for more extensive research in the field of direct targeting of angiogenesis in oncology. Although there is currently no direct tracer that can be singled out, the RGD tracer family seems to show the highest potential therefore we expect one of them to enter the clinical routine.

Introduction Vitamin K antagonists (VKA) and non-vitamin K oral antagonist anticoagulants (NOAC) are used in the clinic to reduce risk of thrombosis. However, they also exhibit vascular off-target effects. The aim of this study is to compare VKA and NOAC on atherosclerosis progression and calcification in an experimental setup. Material and methods Female Apoe(-/-) mice (age 12 weeks) were fed Western-type diet as control or supplemented with dabigatran etexilate or warfarin for 6 or 18 weeks. Vascular calcification was measured in whole aortic arches using mu CT and [F-18]-NaF. Atherosclerotic burden was assessed by (immuno)histochemistry. Additionally, in vitro effects of warfarin, thrombin, and dabigatran on primary vascular smooth muscle cells (VSMC) were assessed. Results Short-term treatment with warfarin promoted formation of atherosclerotic lesions with a pro-inflammatory phenotype, and more rapid plaque progression compared with control and dabigatran. In contrast, dabigatran significantly reduced plaque progression compared with control. Long-term warfarin treatment significantly increased both presence and activity of plaque calcification compared with control and dabigatran. Calcification induced by warfarin treatment was accompanied by increased presence of uncarboxylated matrix Gla protein. In vitro, both warfarin and thrombin significantly increased VSMC oxidative stress and extracellular vesicle release, which was prevented by dabigatran. Conclusion Warfarin aggravates atherosclerotic disease activity, increasing plaque inflammation, active calcification, and plaque progression. Dabigatran lacks undesired vascular side effects and reveals beneficial effects on atherosclerosis progression and calcification. The choice of anticoagulation impacts atherosclerotic disease by differential off target effect. Future clinical studies should test whether this beneficial effect also applies to patients.

Background Personalized molecular radiotherapy based on theragnostics requires accurate quantification of the amount of radiopharmaceutical activity administered to patients both in diagnostic and therapeutic applications. This international multi-center study aims to investigate the clinical measurement accuracy of radionuclide calibrators for 7 radionuclides used in theragnostics: 99m Tc, 111 In, 123 I, 124 I, 131 I, 177 Lu, and 90 Y. Methods In total, 32 radionuclide calibrators from 8 hospitals located in the Netherlands, Belgium, and Germany were tested. For each radionuclide, a set of four samples comprising two clinical containers (10-mL glass vial and 3-mL syringe) with two filling volumes were measured. The reference value of each sample was determined by two certified radioactivity calibration centers (SCK CEN and JRC) using two secondary standard ionization chambers. The deviation in measured activity with respect to the reference value was determined for each radionuclide and each measurement geometry. In addition, the combined systematic deviation of activity measurements in a theragnostic setting was evaluated for 5 clinically relevant theragnostic pairs: 131 I/ 123 I, 131 I/ 124 I, 177 Lu/ 111 In, 90 Y/ 99m Tc, and 90 Y/ 111 In. Results For 99m Tc, 131 I, and 177 Lu, a small minority of measurements were not within ± 5% range from the reference activity (percentage of measurements not within range: 99m Tc, 6%; 131 I, 14%; 177 Lu, 24%) and almost none were outside ± 10% range. However, for 111 In, 123 I, 124 I, and 90 Y, more than half of all measurements were not accurate within ± 5% range ( 111 In, 51%; 123 I, 83%; 124 I, 63%; 90 Y, 61%) and not all were within ± 10% margin ( 111 In, 22%; 123 I, 35%; 124 I, 15%; 90 Y, 25%). A large variability in measurement accuracy was observed between radionuclide calibrator systems, type of sample container (vial vs syringe), and source-geometry calibration/correction settings used. Consequently, we observed large combined deviations (percentage deviation > ± 10%) for the investigated theragnostic pairs, in particular for 90 Y/ 111 In, 131 I/ 123 I, and 90 Y/ 99m Tc. Conclusions Our study shows that substantial over- or underestimation of therapeutic patient doses is likely to occur in a theragnostic setting due to errors in the assessment of radioactivity with radionuclide calibrators. These findings underline the importance of thorough validation of radionuclide calibrator systems for each clinically relevant radionuclide and sample geometry.

The metabolism of ceramides is deregulated in the brain of Alzheimer's disease (AD) patients and is associated with apolipoprotein (APO) APOE4 and amyloid-β pathology. However, how the ceramide metabolism changes over time in AD, in vivo, remains unknown. Distribution and metabolism of [18F]F-HPA-12, a radio-fluorinated version of the ceramide analog N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl) dodecanamide, was investigated in the brain of AD transgenic mouse models (FAD) on an APOE4 or APOE3 genetic background, by positron emission tomography and by gamma counter. We found that FAD mice displayed a higher uptake of [18F]F-HPA-12 in the brain, independently from the APOE4 or APOE3 genetic background. FAD mice could be distinguished from littermate control animals with a sensitivity of 85.7% and a specificity of 87.5%, by gamma counter measurements. Metabolic analysis of [18F]F-HPA-12 in the brain suggested that the tracer is degraded less efficiently in the FAD mice. Furthermore, the radioactive signal registered in the hippocampus correlated with an increase of Cer d18:1/20:2 levels measured in the same brain region by mass spectrometry. Our data gives additional proof that ceramide metabolism is different in FAD mice compared to controls. Ceramide analogs like HPA-12 may function as metabolic probes to study ceramide disbalance in the brain.

BACKGROUND:Lumbar disc herniation is often associated with an inflammatory process. In this context, inflammation has been considered a key factor in the modulation of pain. Here, we present a case of inflammatory activity directly documented in a patient with a lumbar disc herniation.CASE DESCRIPTION:A 49-year-old male presented with progressive low back pain and left-sided S1 radiculopathy, without a focal neurological deficit. The lumbar MR revealed a prominent herniated disc at the L5-S1 level, with compression of the left S1 root. The patient underwent a L5-S1 discectomy using a standard interlaminar approach. Although initially he was pain free, he required three additional operations to address recurrent pain complaints. As research indicates that local inflammation contributes to neuropathic pain, we had the patient undergoes single-photon emission computed tomography (SPECT) imaging using technetium-99m-labeled-infliximab (an anti-tumor necrosis factor [TNF]-alpha monoclonal antibody) before a proposed fourth operation. The SPECT study documented a strong signal at the site of the herniated disc, thus confirming the diagnosis of a pro-inflammatory process involving the S1 nerve root. Nine months after the fourth operation, the patient was pain free. Of interest, the second SPECT study in the now asymptomatic patient demonstrated no detectable/ residual signal at the operative/disc site.CONCLUSION:Absence of a SPECT TNF-alpha signal in a pain-free patient following a lumbar discectomy correlates with the reduction/resolution of the local preoperative inflammatory response.

Brown adipose tissue (BAT) is present in human adults and the current gold standard to visualize and quantify BAT is [ 18 F]FDG PET-CT. However, this method fails to detect BAT under insulin-resistant conditions associated with ageing and weight gain, such as type 2 diabetes. The aim of this study was to develop a novel triglyceride-based tracer for BAT. For this purpose we designed a dual-modal fluorescent/PET fatty acid tracer based on commercially available BODIPY-FL-C 16 , which can be esterified to its correspondent triglyceride, radiolabeled and incorporated into pre-synthesized chylomicron-like particles. BODIPY-FL-C 16 was coupled to 1,2-diolein with a subsequent radiolabeling step resulting in [ 18 F]BODIPY-C 16 -triglyceride that was incorporated into chylomicron-like particles. Various quality control steps using fluorescent and radioactive methods were conducted before BAT visualization was tested in mice. Triglyceride synthesis, radiolabeling and subsequent incorporation into chylomicron-like particles was carried out in decent yields. This radiotracer appeared able to visualize BAT in vivo , and the uptake of the radiotracer was stimulated by cold exposure. The here reported method can be used to incorporate radiolabeled triglycerides into pre-synthesized chylomicron-like particles. Our approach is feasible to visualize and quantify the uptake of triglyceride-derived fatty acids by BAT.

PurposeReliable quantification of radioactivity in nuclear medicine is becoming increasingly important in various therapeutic applications requiring a high accuracy of nuclear medicine measuring equipment, such as radionuclide calibrators. In this study the accuracy of four different radionuclide calibrators was assessed for 99mTc, 111In, 68Ga and 18F for measurement geometries clinically used.MethodsSyringes and vials were prepared with a reference activity using a stock solution of which the activity concentration was determined using gamma-ray spectroscopy. The accuracy of four different radionuclide calibrator systems, ISOMED 2000, ISOMED 2010, VIK-202 and Capintec CRC-25R, was assessed by comparing the measured activity to the reference activity.ResultsDeviations in measured activity from reference values were found up to 12.5%, 32.0%, 29.0% and 12.6% for 99mTc, 111In, 68Ga and 18F, respectively. For 68Ga all radionuclide calibrators systematically overestimated the activity by 10–20%. For 111In, large differences in activity measurements were observed between different source geometries, in particular between syringes and vials. Deviations between radionuclide calibrator systems were found up to 11.8%, 44.4%, 14.4% and 8.7% for 99mTc, 111In, 68Ga and 18F, respectively. When comparing similar syringe types of different brands filled with identical stock solution volume, deviations up to 1.8%, 5.8%, 10.2% and 3.2% were found for 99mTc, 111In, 68Ga and 18F.ConclusionSubstantial deviations in measured activity were found for all radionuclides and radionuclide calibrators, which may result in erroneous activity dosing and image quantification. This underlines the importance of thorough validation of radionuclide calibrators for all measurement geometries and radionuclides clinically used.