Alternative Tracers Research Articles

Validation of the C-X-C chemokine receptor 3 (CXCR3) as a target for PET imaging of T cell activation

PurposeCXCR3 is expressed on activated T cells and plays a crucial role in T-cell recruitment to the tumor microenvironment (TME) during cell-based and immune checkpoint inhibitor (ICI) immunotherapy. This study utilized a 64Cu-labeled NOTA-α-CXCR3 antibody to assess CXCR3 expression in the TME and validate it as a potential T cell activation biomarker in vivo.ProceduresCXCR3+ cells infiltrating MC38 tumors (B57BL/6 mice, untreated and treated with αPD-1/αCTLA-4 ICI) were quantified using fluorescence microscopy and flow cytometry. A commercial anti-mouse CXCR3 antibody (α-CXCR3) was site-specifically conjugated with 2,2,2-(1,4,7-triazacyclononane-1,4,7-triyl)triacetic acid (NOTA) and radiolabeled with 64Cu. Saturation binding of [64Cu]Cu-NOTA-α-CXCR3 was investigated using CHO cells stably transfected with murine CXCR3. Biodistribution and PET imaging studies both at baseline and after 1 to 3 cycles of ICI, respectively, were carried out using different molar activities (10 GBq/µmol to 300 GBq/µmol) of [64Cu]Cu-NOTA-α-CXCR3.ResultsFlow cytometry analysis at baseline confirmed the presence of CXCR3 + T-cells in MC38 tumors, which was significantly increased at day five after ICI (treated 33.8 ± 17.4 vs. control 8.8 ± 6.2 CD3+CXCR3+ cells/mg). These results were qualitatively and quantitatively confirmed by immunofluorescence of tumor cryoslices. In vivo PET imaging of MC38 tumor bearing mice before, during and after ICI using [64Cu]Cu-NOTA-α-CXCR3 (Kd = 3.3 nM) revealed a strong dependence of CXCR3-specificity of tracer accumulation in secondary lymphoid organs on molar activity. At 300 GBq/µmol (1.5 µg of antibody/mouse), a specific signal was observed in lymph nodes (6.33 ± 1.25 control vs. 3.95 ± 1.23%IA/g blocking) and the spleen (6.04 ± 1.02 control vs. 3.84 ± 0.79%IA/g blocking) at 48 h p.i. Spleen-to-liver ratios indicated a time dependent systemic immune response showing a steady increase from 1.08 ± 0.19 (untreated control) to 1.54 ± 0.14 (three ICI cycles).ConclusionsThis study demonstrates the feasibility of in vivo imaging of CXCR3 upregulation under immunotherapy using antibodies. However, high molar activities and low antibody doses are essential for sensitive detection in lymph nodes and spleen. Detecting therapy-induced changes in CXCR3+ T cell numbers in tumors was challenging due to secondary antibody-related effects. Nonetheless, CXCR3 remains a promising target for imaging T cell activation, with anticipated improvements in sensitivity using alternative tracers with high affinities and favorable pharmacokinetics.

Threshold for defining PSMA-positivity prior to 177Lu-PSMA therapy: a comparison of [68Ga]Ga-PSMA-11 and [18F]F-DCFPyL in metastatic prostate cancer

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.

Negative methylene diphosphonate scintigraphy in biopsy-confirmed hereditary transthyretin Ala117Ser cardiac amyloidosis: a case report

99mTc-pyrophosphate (99mTc-PYP) scintigraphy is highly sensitive and specific for the diagnosis of transthyretin cardiac amyloidosis (ATTR-CA). Commonly used alternative tracers included 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) and 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP). A 61-year-old Chinese man presented with signs indicative of left ventricular hypertrophy. Genetic testing revealed heterozygous transthyretin Ala117Ser mutation. Scintigraphy using 99mTc-methylene diphosphonate failed to show myocardial uptake. Five months later, the patient underwent permanent pacemaker implantation. Tafamidis was used irregularly, and the patient died 2 years later. 99mTc-methylene diphosphonate may not be appropriate for diagnostic use in ATTR-CA patient with transthyretin Ala117Ser mutation.

Flow partitioning modelling using high-resolution electrical conductivity data during variable flow conditions in a tropical montane catchment

Tracer-aided hydrological models (TAHMs) are one of the most powerful tools to identify new (event) and old (pre-event) water fractions contributing to stormflow because they account both for streamflow and tracer mixing dynamics in model calibration. Nevertheless, their representativeness of hydrograph dynamics is often limited due to the unavailability of high-resolution conservative tracer data (e.g., water stable isotopes or chloride). Hence, there is a need to identify alternative tracers yielding similar flow partitioning results than “ideal” ones while requiring fewer financial resources for high-frequency monitoring (e.g., sub-hourly). Here, we compare flow partitioning results of a TAHM calibrated using high-frequency electrical conductivity (EC) and water stable isotope (18O) data collected during 37 rainfall-runoff events monitored during variable hydrometeorological conditions in the Zhurucay Ecohydrological Observatory, a tropical alpine catchment located in southern Ecuador. When the model was calibrated using the sampling resolution of stables isotopes (6-hours to 1-hour), no statistically significant differences of pre-event water fractions (PEWFs) using both tracers for model calibration were found. PEWF differences between both tracers for 89% of the events were < 20% regardless of the events’ antecedent moisture and rainfall conditions. Model transfer functions were also similar suggesting that catchment internal processes inferred using both tracers are comparable. Events presenting larger differences (n = 4; up to 27% PEWF difference) had no samples collected during peak flow. Calibration of the model using EC data collected at sub-hourly intervals (every 5-minutes) showed a significant increase in model performance as compared to the frequency of collection of isotopic data. Similarity in flow partitioning results can be attributed to a quasi-conservative nature of EC due to the presence of organic-rich riparian soils (peat-type) overlying compact bedrock across the catchment. Findings also highlight the importance of capturing rapidly occurring catchment mixing processes though high-temporal frequency monitoring of tracer data. Our study encourages the value of assessing the use of alternative tracers, such as EC, to identify fast occurring rainfall-runoff processes, while lowering the costs needed to implement and sustain tracer data collection for long time periods.

Applying geochemical and colour properties to quantify sediment sources in a Brazilian semiarid ephemeral river system

• The Brazilian semiarid is the most densely populated dry region in the world. • Sediment source apportionment was quantified in a semiarid ephemeral catchment. • The combination of conventional and alternative tracers improved source discrimination. • Our results may gain high visibility given the climate change projections for the semiarid regions. The Brazilian semiarid is the most densely populated dry region in the world. Although climate change projections underline the need for the creation of integrated strategies to protect water resources in the semiarid, sediment source apportionment data remain scant for this environment. Accordingly, we evaluated sediment source contributions in one of the most relevant Brazilian semiarid catchments by combining geochemical and colour tracer properties. In doing so, we explored the applicability of colour tracers as a low-cost alternative to the use of time-consuming and costly properties, such as geochemical tracers. Two source classification schemes were used based on environmentally contrasting regions within the catchment (upper, middle and lower catchment parts) and land use (Caatinga biome - natural vegetation, unpaved roads, and channel banks). Suspended sediments (SS) and bed sediments (BS) were used as target sediment. A total of 660 individual source material samples were collected and composited. Geochemical and colour tracers were measured on the source and target sediment samples and used as potential fingerprints to discriminate and quantify the sediment source contributions. The geochemical tracers provided weak source discrimination based on land use. However, combining geochemical and colour tracers improved the final outputs. Using the MixSIAR model, the lower catchment contributed more sediment than the other regional sources. The Caatinga (SS = 49 %; BS = 47 %) contributed more sediment than channel banks (SS = 35 %; BS = 39 %). Overall, our results suggest that the recovery and conservation of the Caatinga vegetation and the stabilization of channel banks, especially in the lower catchment part, are critical for improving sediment supply control in the semiarid study basin. More studies are needed to evaluate the conservative behaviour of colour tracers in ephemeral rivers.

Comparison of [18F]fluciclovine and [18F]FDG PET/CT in Newly Diagnosed Multiple Myeloma Patients

Purpose[18F]FDG PET/CT in multiple myeloma (MM) is currently the best technology to demonstrate patchy and extramedullary disease. However, [18F]FDG PET has some limitations, and imaging with alternative tracers should be explored. In this study, we aimed to evaluate the performance of [18F]fluciclovine PET compared to [18F]FDG PET in newly diagnosed MM patients.ProceduresThirteen newly diagnosed transplant eligible MM patients were imaged both with [18F]FDG PET/CT and [18F]fluciclovine PET/CT within 1 week in a prospective study. The subjects were visually assessed positive or negative for disease. The number of lesions and the SUVmax of selected lesions were measured for both tracers. Furthermore, tracer uptake ratios were obtained by dividing lesion SUVmax by blood or bone marrow SUVmax. Between-group differences and correlations were assessed with paired t-tests and Pearson tests. Bone marrow SUVs were compared to bone marrow plasma cell percentage in biopsy samples.ResultsNine subjects were assessed positively by [18F]FDG PET (69%) and 12 positives by [18F]fluciclovine PET (92%). All positive subjects had [18F]fluciclovine scans that were qualitatively scored as easier to interpret visually than the [18F]FDG scans. The number of lesions was also higher; seven of nine subjects with distinct hot spots on [18F]fluciclovine PET had fewer or no visible lesions on [18F]FDG PET. The mean lesion SUVmax values were 8.2 and 3.8 for [18F]fluciclovine and [18F]FDG, respectively. The mean tumour to blood values were 6.4 and 2.0 for [18F]fluciclovine and [18F]FDG, and the mean ratios between tumour and bone marrow were 2.1 and 1.5 for [18F]fluciclovine and [18F]FDG. The lesion SUVmax and ratios were significantly higher for [18F]fluciclovine (all p < 0.01).Local [18F]fluciclovine SUVmax or SUVmean values in os ilium and the percentage of plasma cells in bone marrow biopsies were linearly correlated (p = 0.048). There were no significant correlations between [18F]FDG SUVs and plasma cells (p = 0.82).ConclusionsBased on this pilot study, [18F]fluciclovine is a promising tracer for MM. The visual and semi-quantitative evaluations indicate that [18F]fluciclovine PET/CT can out-perform [18F]FDG PET/CT at diagnosis.

A Prospective Study Evaluating the Accuracy of Indocyanine Green (ICG) Fluorescence Compared with Radioisotope for Sentinel Lymph Node (SLN) Detection in Early Breast Cancer.

Dual localization methods with blue dye and radioisotope represents the standard method for SLN identification. Side effects of blue dye and problems with access to radioisotope has prompted assessment of alternative tracers. This study has evaluated a combination of indocyanine green (ICG) fluorescence with radioisotope for SLN biopsy in early breast cancer. In a prospective observational study 79 patients scheduled for SLN biopsy underwent dual localization with radioisotope nanocolloid and ICG (0.5%). The primary goal was to assess noninferiority of ICG compared with standard radioisotopic localization. Statistical analysis was performed using Stata (version 15.1). A total of 162 nodes were retrieved from 79 patients with an average nodal count of 2.04 (range 1-4) and an overall identification rate of 98.7% (78/79). Nodal detection rates for ICG alone or combined with radioisotope were 98.1% (151/154) and 73.4% (113/154) respectively. Metastasis were present in 13 nodes, all of which were both fluorescent and radioactive and distributed amongst 13 patients each with a single positive node containing macrometastases (n = 5), micrometastases (n = 6), or isolated tumor cells (n = 2). ICG was noninferior to radioisotope with the lower confidence interval not crossing within the predefined limit. No serious adverse reactions were recorded. These results confirm comparable performance parameters for ICG to the "gold standard" using radioisotope. ICG can reliably be employed as a sole tracer that avoids potential drawbacks of standard tracer agents, including availability and costs of radioisotope.

New Targets for PET Imaging of Myeloma

Recent advances in the treatment of multiple myeloma (MM) have increased the need for accurate diagnosis and detection of minimal residual disease (MRD), disease characterization and localization, and response evaluation and prognostication. Positron emission tomography (PET)/computed tomography (CT) imaging combines molecular and morphological information and has been shown to be especially valuable in this disease. The most frequently used PET tracer in MM is the glucose analog 18F-fluorodeoxyglucose ([18F]FDG). [18F]FDG PET/CT has a sensitivity for detection of MM between 80% to 100% and is currently the main imaging modality for assessing treatment response and for determining MRD. However, 18F-FDG PET/CT has some limitations, and imaging with alternative tracers that may overcome these constraints should be further explored. This article discusses new targets for PET/CT imaging in the assessment of MM.

Molecules with ALMA at Planet-forming Scales. XX. The Massive Disk around GM Aurigae

Abstract Gas mass remains one of the most difficult protoplanetary disk properties to constrain. With much of the protoplanetary disk too cold for the main gas constituent, H2, to emit, alternative tracers such as dust, CO, or the H2 isotopologue HD are used. However, relying on disk mass measurements from any single tracer requires assumptions about the tracer’s abundance relative to H2 and the disk temperature structure. Using new Atacama Large Millimeter/submillimeter Array (ALMA) observations from the Molecules with ALMA at Planet-forming Scales (MAPS) ALMA Large Program as well as archival ALMA observations, we construct a disk physical/chemical model of the protoplanetary disk GM Aur. Our model is in good agreement with the spatially resolved CO isotopologue emission from 11 rotational transitions with spatial resolution ranging from 0.″15 to 0.″46 (24–73 au at 159 pc) and the spatially unresolved HD J = 1–0 detection from Herschel. Our best-fit model favors a cold protoplanetary disk with a total gas mass of approximately 0.2 M ⊙, a factor of 10 reduction in CO gas inside roughly 100 au and a factor of 100 reduction outside of 100 au. Despite its large mass, the disk appears to be on the whole gravitationally stable based on the derived Toomre Q parameter. However, the region between 70 and 100 au, corresponding to one of the millimeter dust rings, is close to being unstable based on the calculated Toomre Q of &lt;1.7. This paper is part of the MAPS special issue of the Astrophysical Journal Supplement.

Metallicity Dependence of the H/H2 and C+/C/CO Distributions in a Resolved Self-regulating Interstellar Medium

Abstract We study the metallicity dependence of the H/H2 and C+/C/CO distributions in a self-regulated interstellar medium (ISM) across a broad range of metallicities (0.1 &lt; Z/Z ⊙ &lt; 3). To this end, we conduct high-resolution (particle mass of 1 M ⊙) hydrodynamical simulations coupled with a time-dependent H2 chemistry network. The results are then post-processed with an accurate chemistry network to model the associated C+/C/CO abundances, based on the time-dependent non-steady-state (“nonequilibrium”) H2 abundances. We find that the time-averaged star formation rate and the ISM structure are insensitive to metallicity. The column densities relevant for molecular shielding appear correlated with the volume densities in gravitationally unstable gas. As metallicity decreases, H2 progressively deviates from steady state (“equilibrium”) and shows shallow abundance profiles until they sharply truncate at the photodissociation fronts. In contrast, the CO profile is sharp and controlled by photodissociation as CO quickly reaches steady state. We construct effective 1D cloud models that successfully capture the time-averaged chemical distributions in simulations. At low metallicities, the steady-state model significantly overestimates the abundance of H2 in the diffuse medium. The overestimated H2, however, has little impact on CO. Consequently, the mass fraction of CO-dark H2 gas is significantly lower than what a fully steady-state model predicts. The mass ratios of H2/C+ and H2/C both show a weaker dependence on Z ′ than H2/CO, which potentially indicates that C+ and C could be alternative tracers for H2 at low Z ′ in terms of mass budget. Our chemistry code for post-processing is publicly available.

Measuring the Average Molecular Gas Content of Star-forming Galaxies at z = 3–4

Abstract We study the molecular gas content of 24 star-forming galaxies at z = 3–4, with a median stellar mass of 109.1 M ⊙, from the MUSE Hubble Ultra Deep Field (HUDF) Survey. Selected by their Lyα λ1216 emission and H F160W-band magnitude, the galaxies show an average 〈 EW Ly α 0 〉 ≈ 20 Å, below the typical selection threshold for Lyα emitters ( EW Ly α 0 &gt; 25 Å), and a rest-frame UV spectrum similar to Lyman-break galaxies. We use rest-frame optical spectroscopy from KMOS and MOSFIRE, and the UV features observed with MUSE, to determine the systemic redshifts, which are offset from Lyα by 〈Δv(Lyα)〉 = 346 km s−1, with a 100 to 600 km s−1 range. Stacking 12CO J = 4 → 3 and [C i]3P1 → 3P0 (and higher-J CO lines) from the ALMA Spectroscopic Survey of the HUDF, we determine 3σ upper limits on the line luminosities of 4.0 × 108 K km s−1pc2 and 5.6 × 108 K km s−1pc2, respectively (for a 300 km s−1 line width). Stacking the 1.2 mm and 3 mm dust-continuum flux densities, we find a 3σ upper limits of 9 μJy and 1.2 μJy, respectively. The inferred gas fractions, under the assumption of a “Galactic” CO-to-H2 conversion factor and gas-to-dust ratio, are in tension with previously determined scaling relations. This implies a substantially higher α CO ≥ 10 and δ GDR ≥ 1200, consistent with the subsolar metallicity estimated for these galaxies ( 12 + log ( O / H ) ≈ 7.8 ± 0.2 ). The low metallicity of z ≥ 3 star-forming galaxies may thus make it very challenging to unveil their cold gas through CO or dust emission, warranting further exploration of alternative tracers, such as [C ii].

The Role of Molecular Imaging in a Muscle-Invasive Bladder Cancer Patient: A Narrative Review in the Era of Multimodality Treatment.

Diagnostic imaging in bladder cancer plays an important role since it is needed from pretreatment staging to follow-up, but a morphological evaluation performed with both CT and MRI showed low sensitivities and specificities in detecting pathologic lymph nodes, due to the occurrence of false positive results. Implementation of functional information provided by PET/CT could be a determinant in the management of patients with muscle-invasive bladder cancer. A focus on the role of 18F-FDG PET/CT and alternative tracers in patients with muscle-invasive bladder cancer is provided in this analysis in order to outline its potential applications in staging settings and response evaluation after neoadjuvant chemotherapy.

An application of aromatic compounds as alternative tracers of tsunami backwash deposits

This manuscript provides some comprehensive technical insights regarding the application of polycyclic aromatic hydrocarbons (PAHs) characterized by using Gas-Chromatography Mass Spectrometry. Although numerous chemical species such as water soluble ionic species (e.g. Na+, K+, Cl−, Ca2+, Mg2+) and acid leachable heavy metal fractions (e.g. Fe, Cd, Al, Mo, Sb, As, Cu, Zn, Pb, and Mn) can be used to characterize tsunami deposits, the knowledge of PAH congeners as alternative chemical species for identifying tsunami backwash deposits is strictly limited. This manuscript is exclusive because it aims to find some alternative chemical proxies in order to distinguish tsunami backwash deposits from typical marine sediments. A wide range of diagnostic binary ratios of PAH congeners have been selected in order to characterize Typical Marine Sediments (TMS), Tsunami backwash deposits (TBD), Onshore Tsunami Deposits (OTD) and Coastal Zone Soils (CZS). The state of the art and future perspectives coupled with both advantages and disadvantages of above mentioned chemical tracers will be critically reviewed and further discussed.

Intraoperative laparoscopic detection of sentinel lymph nodes with indocyanine green and superparamagnetic iron oxide in a swine gallbladder cancer model.

Mapping of sentinel lymph nodes (SLNs) can enable less invasive surgery. However, mapping is challenging for cancers of difficult-to-access visceral organs, such as the gallbladder, because the standard method using radioisotopes (RIs) requires preoperative tracer injection. Indocyanine green (ICG) and superparamagnetic iron oxide (SPIO) have also been used as alternative tracers. In this study, we modified a previously reported magnetic probe for laparoscopic use and evaluated the feasibility of detecting SLNs of the gallbladder using a laparoscopic dual tracer method by injecting ICG and SPIO into five swine and one cancer-bearing swine. The laparoscopic probe identified SPIO nanoparticles in the nodes of 4/5 swine in situ, the magnetic field counts were 2.5–15.9 μT, and fluorescence was detected in SLNs in all five swine. ICG showed a visual lymph flow map, and SPIO more accurately identified each SLN with a measurable magnetic field quite similar to the RI. We then developed an advanced gallbladder cancer model with lymph node metastasis using recombination activating gene 2-knockout swine. We identified an SLN in the laparoscopic investigation, and the magnetic field count was 3.5 μT. The SLN was histologically determined to be one of the two metastatic lymph nodes. In conclusion, detecting the SLNs of gallbladder cancer in situ using a dual tracer laparoscopic technique with ICG and SPIO was feasible in a swine model.

ADDED VALUE OF POSITRON EMISSION TOMOGRAPHY/ COMPUTED TOMOGRAPHY IN DETECTION OF PERITONEAL CARCINOMATOSIS

The peritoneum consists of 2 layers the parietal layer covering the inner surface of abdomen and visceral layer which reflects over and surround the abdominal organs. Peritoneal carcinomatosis is one of the frequent sites of metastasis in many gastrointestinal and gynecological tumors mostly colorectal and ovarian cancer. Various forms of peritoneal carcinomatosis could be noted in the form of ascites, micronodular, nodular, plaque like, mass like, omental cake, teca aspect and ileal freezing.Positron emission tomography (PET) is being increasingly used for diagnosis, staging, and follow-up of various malignancies. In peritoneal carcinomatosis, FDG-PET/CT has been shown to have higher sensitivity and positive predictive value (up to 92%) compared to FDG-PET and CT alone. It also has higher specificity (up to 97%) compared to FDG-PET alone, with similar specificity compared to CT alone. It is more useful than just PET the addition of CT allows better anatomic visualization and can detect the presence of cancer lesions based on the glucose uptake of the cells. It identifies the exact localization and area of the peritoneal metastasis, PET-CT provides better accuracy. It adds good value to the conventional imaging mainly for monitoring response to the therapy, especially on long-term follow-up. PET/CT has multiple clinical applications in peritoneal oncology detecting the primary tumor in unknown primary, tumor staging and restaging; treatment planning, post therapy response, differentiating recurrence from post therapy changes; distinguishing malignant from benign peritoneal disease; can be used as a biomarker as well as alternative tracers for cancer evaluation.

The value of 18F-PSMA-1007 PET/CT in identifying non-metastatic high-risk prostate cancer

BackgroundClinical management decisions on prostate cancer (PCa) are often based on a determination of risk. 68Ga-prostate-specific membrane antigen (PSMA)-11-positron emission tomography (PET)/computer tomography (CT) is an attractive modality to assess biochemical recurrence of PCa, detect metastatic disease and stage of primary PCa, making it a promising strategy for risk stratification. However, due to some limitation of 68Ga-PSMA-11 the development of alternative tracers is of high interest. In this study, we aimed to investigate the value of 18F-PSMA-1007 in identifying non-metastatic high-risk PCa.MethodsA total of 101 patients with primary non-metastatic PCa who underwent 18F-PSMA-1007 PET/CT were retrospectively analyzed. According to the European Association of Urology guidelines on PCa, patients were classified into intermediate-risk (IR) group or high-risk (HR) group. The maximum standardized uptake values (SUVmax) of the primary prostate tumor were measured on PET/CT images. The diagnostic performance of PET/CT for IR and HR PCa was calculated, and the relationship between the SUVmax of primary prostate tumor, prostate-specific antigen (PSA) level and Gleason score (GS) was analyzed.ResultsOf all 101 patients, 49 patients were classified into IR group and 52 patients were classified into HR group. There was a significant positive correlation between PSA level/GS and SUVmax (r = 0.561, r = 0.496, P < 0.001, respectively). Tumors with GS 6 and 7a showed significantly lower 18F-PSMA-1007 uptake compared to patients with GS 8 and 9 (P < 0.01). SUVmax in patients of HR was significantly higher than those of IR (median SUVmax: 16.85 vs 7.80; P < 0.001). In receiver operating characteristic curve analysis, the optimal cutoff value of the SUVmax for identifying high-risk PCa was set as 9.05 (area under the curve: 0.829; sensitivity: 90.4%; specificity: 65.3%).Conclusion18F-PSMA-1007 PET/CT showed the powerful diagnosis efficacy for high-risk PCa, which can be used as an objective imaging reference index for clinical reference.

Combining spectroscopy and magnetism with geochemical tracers to improve the discrimination of sediment sources in a homogeneous subtropical catchment

An important step in the sediment source fingerprinting approach is the selection of the appropriate tracing parameters to maximize source discrimination. The use of multiple tracing properties may reduce uncertainties and increase discrimination between sources. Accordingly, this study investigates the discrimination and quantifies the contribution of sediment sources delivering sediment to a river draining a homogeneous subtropical agricultural catchment based on the combination of ultraviolet–visible spectra derived parameters (UV), magnetic (M), and geochemical tracers (GEO). The investigated catchment (Conceição River − 804 km2), located in Southern Brazil, has predominantly deep and strongly weathered Ferralsols. The main land-uses found in the area are cropland (89%), pasture (5%) and forest (5%). A total of 187 samples were collected to characterise the five main sediment sources, including cropland, pastures, unpaved roads, gullies and stream banks. A total of 53 tracers, including 21 geochemical tracers, two magnetic properties and 30 parameters derived from UV spectra, were analysed. Tracers were selected following a three step procedure, including: (i) an interquartile range test, (ii) a Kruskal–Wallis H test, and (iii) a linear discriminant function analysis (LDA). The LDA was performed using six different sets of variables: (i) GEO only; (ii) UV only; (iii) M + UV (MUV); (iv) GEO + UV (GUV); (v) GEO + M (GM) and (vi) GEO + M + UV (GMUV). The selected tracers were introduced into a mass balance mixing model to estimate the source contributions to in-stream sediment by minimizing the sum of square residuals. Most geochemical tracers were considered not conservative by using the interquartile range test in this catchment with highly weathered soils. The GM approach resulted in the highest percentage of samples correctly classified (SCC), with 74%, followed by the approaches with GMUV and GUV, with 73%. Alternative tracers, UV individually or combined with M tracers, correctly classified only 59 and 60% of the samples, respectively. Moreover, they did not provide significant additional discrimination power even when combined with the GEO tracers. The apportionment model resulted in similar source contribution results for all approaches, with the absence of significant difference when comparing the mean source contributions obtained for the entire set of sediment samples (Cropland: 17–23%; Pastures: 24–34%; Unpaved Roads: 3–12%; Stream Banks: 26–31%; Gullies: 14–19%). Due to the strong homogeneity of soil types found in the Conceição catchment, these differences in source contributions remained very low and the results of the mixing model were impacted by the high number of potential sources and the relatively limited quality of the sediment source discrimination. According to the model results, the low discrimination between the potential sediment sources illustrates the difficulties for discriminating land-used based sediment sources, with more than three potential sources, in homogeneous catchments with highly weathered soils (e.g. Ferralsols, Nitisols) under tropical conditions.

Developing a new passive tracer gas test for air change rate measurement

Ventilation is critical in interpreting indoor air quality (IAQ), yet most IAQ assessments do not report ventilation adequately. Most ventilation assessments use tracer gas tests (TGT) to measure total air change rate (ACH), but currently applied TGTs present three shortcomings: limited comparability between ACH and IAQ data, inadequate substances employed as tracer gases and tendency to bias arising from perfect-mixing assumption. This paper proposes a new TGT approach, employing an alternative tracer gas that is captured/analysed using commercial passive IAQ-samplers and including a careful planning-phase to account for imperfect-mixing. Two substances were selected as potential alternative tracers: 2-butoxyethyl-acetate (EGBEA) and deuterated decane (D-decane). Tracer-source tests were performed in lab, enabling enhancements to the source design. Results indicated RH influence over the emissions rates, and EGBEA’s use as tracer was discarded due to hygroscopy. Further work includes evaluating D-decane’s behaviour under varying conditions and computer-simulating TGTs to study the imperfect-mixing effects.

CBMT-03. EVALUATION OF PET TRACERS TO DIFFERENTIATE IDH1 MUTANT GBM

Abstract OBJECTIVE PET/CT offers the unique potential to noninvasively evaluate biomarker expression and aberrant metabolism. 18F-FDG has driven PET/CT to the forefront of cancer imaging, as altered glucose metabolism is a hallmark of oncogenesis. However, 18F-FDG is suboptimal for GBM due to high physiologic uptake in normal brain. The development of alternative tracers has reignited the field of PET/CT in GBM and offers hope for diagnosis and molecular staging in GBM. We hypothesize that fundamental differences in metabolism and oncogene expression present in IDH1 mutatant gliomas can be shown using PET imaging, as has been suggested in some correlative clinical studies. Our objective was therefore to establish a causal link between IDH1 mutation in GBM and uptake of targeted PET tracers in a unique proneural GBM transgenic model characterized by p53, IDH1 mutations and PDGF expression. METHODS We examined the uptake of 3 blood-brain-barrier (BBB) penetrant tracers that have been used in GBM: (a) 18F-FDG, a surrogate for increased glycolysis; (b) 18F-Fluciclovine, an amino acid derivative transported into cells through the energy-independent L-type amino acid transporter (LAT) system and is approved by the FDA for prostate cancer; and (c) 11C-ER176, a tracer that binds the TSPO receptor that is generally expressed on activated microglia as well as GBM. RESULTS We did not observe significant differences in 18F-FDG uptake between wt and IDH mutant GBM cells. However, we found that IDH mutant GBM cells demonstrated significantly increased 18F-Fluciclovine (47%) and 11C-ER176 (53%) versus IDH wt cells. CONCLUSION We have established a causal link between IDH mutation status and uptake of (a) 18F-Fluciclovine, a promising FDA approved PET tracer and (b) 11C-ER176, a second generation TSPO ligand. Thus, we are performing further studies in orthotopic syngeneic GBM models to determine if PET imaging can non-invasively demonstrate molecular characterization and therapeutic stratification in glioma.

Feasibility of sentinel lymph node mapping of the ovary: a systematic review

Pelvic and para-aortic lymphadenectomy is routinely performed in early ovarian cancer to define the stage of the disease. However, it may be associated with increased blood loss, operative time, and...