Purpose Patient-specific dosimetry is required to ensure the safety of molecular radiotherapy and to predict response. Dosimetry involves several steps, the first of which is the determination of the activity of the radiopharmaceutical taken up by an organ/lesion over time. As uncertainties propagate along each of the subsequent steps (integration of the time–activity curve, absorbed dose calculation), establishing a reliable activity quantification is essential. The MRTDosimetry project was a European initiative to bring together expertise in metrology and nuclear medicine research, with one main goal of standardizing quantitative 177Lu SPECT/CT imaging based on a calibration protocol developed and tested in a multicentre inter-comparison. This study presents the setup and results of this comparison exercise. Methods The inter-comparison included nine SPECT/CT systems. Each site performed a set of three measurements with the same setup (system, acquisition and reconstruction): (1) Determination of an image calibration for conversion from counts to activity concentration (large cylinder phantom), (2) determination of recovery coefficients for partial volume correction (IEC NEMA PET body phantom with sphere inserts), (3) validation of the established quantitative imaging setup using a 3D printed two-organ phantom (ICRP110-based kidney and spleen). In contrast to previous efforts, traceability of the activity measurement was required for each participant, and all participants were asked to calculate uncertainties for their SPECT-based activities. Results Similar combinations of imaging system and reconstruction lead to similar image calibration factors. The activity ratio results of the anthropomorphic phantom validation demonstrate significant harmonization of quantitative imaging performance between the sites with all sites falling within one standard deviation of the mean values for all inserts. Activity recovery was underestimated for total kidney, spleen, and kidney cortex, while it was overestimated for the medulla. Conclusion This international comparison exercise demonstrates that harmonization of quantitative SPECT/CT is feasible when following very specific instructions of a dedicated calibration protocol, as developed within the MRTDosimetry project. While quantitative imaging performance demonstrates significant harmonization, an over- and underestimation of the activity recovery highlights the limitations of any partial volume correction in the presence of spill-in and spill-out between two adjacent volumes of interests.

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The optimised delivery of Molecular Radiotherapy requires individualised calculation of absorbed dose to both targeted lesions and neighbouring healthy tissue. To achieve this, accurate quantification of the activity distribution in the patient by external detection is vital. Methods: This work extends specific anatomy-related calibration to true organ shapes. A set of patient-specific 3D printed organ inserts based on a diagnostic CT scan was produced, comprising the liver, spleen and both kidneys. The inserts were used to calculate patient-specific calibration factors for 177 Lu. These calibration factors were compared with previously reported calibration factors for corresponding organ models based on the Cristy and Eckerman phantom series and for a comparably sized sphere. Monte Carlo calculations of the patientspecific radiation dose were performed for comparison with current clinical dosimetry methods for these data. Results: Patient-specific calibration factors are shown to be dependent on the volume, shape and position of the organ containing activity with a corresponding impact on the calculation of the dose to the patient. The impact of organ morphology on calculated dose is reduced when the dominant contributor to dose is beta particles. This is due to the small range of beta particles in tissue. Overestimations of recovered activity and hence dose of up to 135% are observed. Conclusion: For accurate quantification to be performed calibration factors accounting for organ size, shape and position must be used. Such quantification is vital if accurate, patient-specific dosimetry is to be achieved.

The skeletal muscle ATP-sensitive K (K) channel is crucial in preventing fiber damage and contractile dysfunction, possibly by preventing damaging ATP depletion. The objective of this study was to investigate changes in energy metabolism during fatigue in wild-type and inwardly rectifying K channel (Kir6.2)-deficient (Kir6.2) flexor digitorum brevis (FDB), a muscle that lacks functional K channels. Fatigue was elicited with one tetanic contraction every second. Decreases in ATP and total adenylate levels were significantly greater in wild-type than Kir6.2 FDB during the last 2 min of the fatigue period. Glycogen depletion was greater in Kir6.2 FDB for the first 60 s, but not by the end of the fatigue period, while there was no difference in glucose uptake. The total amount of glucosyl units entering glycolysis was the same in wild-type and Kir6.2 FDB. During the first 60 s, Kir6.2 FDB generated less lactate and more CO; in the last 120 s, Kir6.2 FDB stopped generating CO and produced more lactate. The ATP generated during fatigue from phosphocreatine, glycolysis (lactate), and oxidative phosphorylation (CO) was 3.3-fold greater in Kir6.2 than wild-type FDB. Because ATP and total adenylate were significantly less in Kir6.2 FDB, it is suggested that Kir6.2 FDB has a greater energy deficit, despite a greater ATP production, which is further supported by greater glucose uptake and lactate and CO production in Kir6.2 FDB during the recovery period. It is thus concluded that a lack of functional K channels results in an impairment of energy metabolism.

Kneeling is often impaired following total knee replacement. There is no clinical study comparing a lateral to a midline skin incision with regard to kneeling. Patients with a well-functioning total knee replacement enrolled in the trial. The participants with a lateral skin incision were matched with those with a standard midline incision. Twenty-two patients were enrolled in the study: 10 had a lateral skin incision, and 12 had a midline incision. Those with a lateral skin incision had a significantly higher Forgotten Joint Score than with a midline skin incision (Difference of Means Lateral vs Midline = 10.9 [p value 0.0098]), and an improved ability to kneel at 110 degrees of flexion (Kneeling Ability Test; Difference of Means Lateral vs Midline = 41.7 [p value 0.020]). These results suggest that a lateral skin incision may provide reduced joint awareness and improved kneeling ability. Further investigation with a randomised controlled trial is needed.

Lanthanide‐based upconverting nanoparticles (UCNPs) are largely sought‐after for biomedical applications ranging from bioimaging to therapy. A straightforward strategy is proposed here using the naturally sourced polymer phytoglycogen to coencapsulate UCNPs with hydrophobic photosensitizers as an optical imaging platform and light‐induced therapeutic agents. The resulting multifunctional sub‐micrometer‐sized luminescent beads are shown to be cytocompatible as carrier materials, which encourages the assessment of their potential in biomedical applications. The loading of UCNPs of various elemental compositions enables multicolor hyperspectral imaging of the UCNP‐loaded beads, endowing these materials with the potential to serve as luminescent tags for multiplexed imaging or simultaneous detection of different moieties under near‐infrared (NIR) excitation. Coencapsulation of UCNPs and Rose Bengal opens the door for potential application of these microcarriers for collagen crosslinking. Alternatively, coloading UCNPs with Chlorin e6 enables NIR‐light triggered generation of reactive oxygen species. Overall, the developed encapsulation methodology offers a straightforward and noncytotoxic strategy yielding water‐dispersible UCNPs while preserving their bright and color‐tunable upconversion emission that would allow them to fulfill their potential as multifunctional platforms for biomedical applications.

A new CEST-MRI contrast agent, 2-HYNIC, capable of sensing aromatic aldehydes is reported. Pyridoxal 5’-phosphate, a key Vitamin B6 metabolite necessary for > 140 biotransformations was mapped by CEST-MRI in...

The use of bovine carpal joints is a cost-effective, safe and easily reproducible model for education on basic anterior cruciate ligament repair skills and technique prior to patient contact.