Errors in Patient Positioning for Bone Mineral Density Assessment by Dual X-Ray Absorptiometry: Effect of Technologist Retraining.

Improper positioning is one of the factors that can lead to incorrect bone mineral density (BMD) results. This study aimed to assess the frequencies of erroneous positioning during three periods: before retraining of the technologists (BR), after retraining (AR), and at the current timepoint 8 years after retraining (C). The BMD images of the first 150 consecutive patients who underwent DXA of the lumbar spine and hip during each of the three periods were retrospectively reviewed. Patients were excluded if they had severe scoliosis, rendering proper positioning impossible. Each BMD image was assessed by an International Society of Clinical Densitometry certified clinical densitometrist who was blinded to the date of the initial examination. For the lumbar spine in the BR group, the criteria frequently not met were inclusion of both iliac crests (33.8%), straightness (30.3%), and midline positioning (20.4%); the respective frequencies were significantly reduced to 0.8%-5.6%, 2.1%-3.0%, and 0%-2.8% in the AR and C groups (p < 0.05). For the hip in the BR group, the criteria frequently not met were straightness (52.8%) and internal rotation (21.8%); the respective frequencies were significantly reduced to 0%-4.2% and 8.3%-8.4% in the AR and C groups (p < 0.05). Overall improper positioning in the BR group was 49.3% and 57.3% at the lumbar spine and the hip, respectively; the respective frequencies were reduced to 9.3% and 12.7% in the AR group, and to 2.7% and 7.3% in the C group. The least significant change values for the lumbar spine, femoral neck, and total hip also became smaller after retraining. Retraining the technologists improved patient positioning, as evidenced by the decreased frequencies of erroneous positioning and the improved least significant change values after the retraining.

[(89)Zr]oxinate4 for long-term in vivo cell tracking by positron emission tomography.

PURPOSE: (111)In (typically as [(111)In]oxinate3) is a gold standard radiolabel for cell tracking in humans by scintigraphy. A long half-life positron-emitting radiolabel to serve the same purpose using positron emission tomography (PET) has long been sought. We aimed to develop an (89)Zr PET tracer for cell labelling and compare it with [(111)In]oxinate3 single photon emission computed tomography (SPECT). METHODS: [(89)Zr]Oxinate4 was synthesised and its uptake and efflux were measured in vitro in three cell lines and in human leukocytes. The in vivo biodistribution of eGFP-5T33 murine myeloma cells labelled using [(89)Zr]oxinate4 or [(111)In]oxinate3 was monitored for up to 14 days. (89)Zr retention by living radiolabelled eGFP-positive cells in vivo was monitored by FACS sorting of liver, spleen and bone marrow cells followed by gamma counting. RESULTS: Zr labelling was effective in all cell types with yields comparable with (111)In labelling. Retention of (89)Zr in cells in vitro after 24 h was significantly better (range 71 to >90%) than (111)In (43-52%). eGFP-5T33 cells in vivo showed the same early biodistribution whether labelled with (111)In or (89)Zr (initial pulmonary accumulation followed by migration to liver, spleen and bone marrow), but later translocation of radioactivity to kidneys was much greater for (111)In. In liver, spleen and bone marrow at least 92% of (89)Zr remained associated with eGFP-positive cells after 7 days in vivo. CONCLUSION: [(89)Zr]Oxinate4 offers a potential solution to the emerging need for a long half-life PET tracer for cell tracking in vivo and deserves further evaluation of its effects on survival and behaviour of different cell types.

Red Marrow Absorbed Dose Calculation in Thyroid Cancer Patient Using a Simplified Excel Spreadsheet

Objectives: Absorbed dose to red marrow (Drm) can be calculated using blood dosimetry. However, this method is laborious and invasive. Therefore, image-based dosimetry is the method of choice. Nonetheless, the commercial software is expensive. The goal of this work was to develop a simplified excel spreadsheet for image-based radioiodine red marrow dosimetry. Methods: The serial whole-body images (acquired at 2nd, 6th, 24th, 48th, and 72th hours) of 29 patients from the routine pretherapeutic dosimetry protocol were retrospectively reanalyzed. The commercial OLINDA/EXM image-based dosimetry software was used to calculate the whole-body time-integrated activity coefficient (TIACWB) and Drm [in terms of absorbed dose coefficient (drm)]. For the simplified excel spreadsheet, the wholebody count was obtained from the vendor-supplied software. Then, the TIACWB was computed by a fitting time-activity curve using an Excel function. S factor was taken from other publications and scaled according to the patient-specific mass. A comparison of the TIACWB and drm from both methods was done using a non-inferiority test using a paired t-test or the Wilcoxon signed-rank test. Results: The TIACWB showed no significant difference between both methods (p=0.243). The calculated Drm from a simplified Excel spreadsheet was assumed to be statistically non-inferior to the commercial OLINDA/EXM image-based dosimetry software with the non-inferiority margin of 0.02 (p<0.05). Conclusion: The dose assessment from a simplified Excel spreadsheet is feasible and relatively low cost compared to the commercial OLINDA/EXM image-based dosimetry software.

Author Correction: Non-Invasive whole-body detection of complement activation using radionuclide imaging in a mouse model of myocardial ischaemia-reperfusion injury.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

18F-Fluorosulfate for PET Imaging of the Sodium-Iodide Symporter: Synthesis and Biologic Evaluation In Vitro and In Vivo.

Anion transport by the human sodium-iodide symporter (hNIS) is an established target for molecular imaging and radionuclide therapy. Current radiotracers for PET of hNIS expression are limited to 124I- and 18F-BF4- We sought new 18F-labeled hNIS substrates offering higher specific activity, higher affinity, and simpler radiochemical synthesis than 18F-BF4- METHODS: The ability of a range of anions, some containing fluorine, to block 99mTcO4- uptake in hNIS-expressing cells was measured. SO3F- emerged as a promising candidate. 18F-SO3F- was synthesized by reaction of 18F- with SO3-pyridine complex in MeCN and purified using alumina and quaternary methyl ammonium solid-phase extraction cartridges. Chemical and radiochemical purity and serum stability were determined by radiochromatography. Radiotracer uptake and efflux in hNIS-transduced HCT116-C19 cells and the hNIS-negative parent cell line were evaluated in vitro in the presence and absence of a known competitive inhibitor (NaClO4). PET/CT imaging and ex vivo biodistribution measurement were conducted on BALB/c mice, with and without NaClO4 inhibition. RESULTS: Fluorosulfate was identified as a potent inhibitor of 99mTcO4- uptake via hNIS in vitro (half-maximal inhibitory concentration, 0.55-0.56 µM (in comparison with 0.29-4.5 µM for BF4-, 0.07 µM for TcO4-, and 2.7-4.7 µM for I-). Radiolabeling to produce 18F-SO3F- was simple and afforded high radiochemical purity suitable for biologic evaluation (radiochemical purity > 95%, decay-corrected radiochemical yield = 31.6%, specific activity ≥ 48.5 GBq/µmol). Specific, blockable hNIS-mediated uptake in HCT116-C19 cells was observed in vitro, and PET/CT imaging of normal mice showed uptake in thyroid, salivary glands (percentage injected dose/g at 30 min, 563 ± 140 and 32 ± 9, respectively), and stomach (percentage injected dose/g at 90 min, 68 ± 21). CONCLUSION: Fluorosulfate is a high-affinity hNIS substrate. 18F-SO3F- is easily synthesized in high yield and very high specific activity and is a promising candidate for preclinical and clinical PET imaging of hNIS expression and thyroid-related disease; it is the first example of in vivo PET imaging with a tracer containing an S-18F bond.

Non-Invasive whole-body detection of complement activation using radionuclide imaging in a mouse model of myocardial ischaemia-reperfusion injury.

Complement activation is a recognised mediator of myocardial ischaemia-reperfusion-injury (IRI) and cardiomyocytes are a known source of complement proteins including the central component C3, whose activation products can mediate tissue inflammation, cell death and profibrotic signalling. We investigated the potential to detect and quantify the stable covalently bound product C3d by external body imaging, as a marker of complement activation in heart muscle in a murine model of myocardial IRI. We used single-photon-emission-computed-tomography (SPECT) in conjunction with 99mTechnecium-labelled recombinant complement receptor 2 (99mTc-rCR2), which specifically detects C3d at the site of complement activation. Compared to control imaging with an inactive CR2 mutant (99mTc-K41E CR2) or an irrelevant protein (99mTc-PSMA) or using 99mTc-rCR2 in C3-deficient mice, the use of 99mTc-rCR2 in complement-intact mice gave specific uptake in the reperfused myocardium. The heart to skeletal muscle ratio of 99mTc-rCR2 was significantly higher than in the three control groups. Histological analysis confirmed specific uptake of 99mTc-rCR2. Following therapeutic inhibition of complement C3 activation, we found reduced myocardial uptake of 99mTc-rCR2. We conclude, therefore that 99mTc-rCR2 imaging can be used for non-invasive detection of activated complement and in future could be exploited to quantify the severity of myocardial damage due to complement activation.