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This study investigates the structural control of the numerous gold occurrences in the southern part of the Barberton Greenstone Belt in the Malolotja and Steynsdorp areas. The gold-bearing event distribution is studied using field structural geology associated with a petrological and microstructural analysis. Three major tectonic events have been identified in quartz veins and direct country rocks. The first event (De) created a regional schistosity (Se), probably associated with an early thrusting event. The second event (Df) is related to a large-scale folding, which formed the anticline at Steynsdorp and synform at Malolotja. It resulted from a main E–W direction of shortening and is responsible for the folding of the Se schistosity. It formed a N–S-striking axial planar cleavage (Sf), observed and associated with the emplacement of the main gold-bearing veins. The mineralised system exhibits a complex vein network, in which shallow dipping veins have developed coevally with steep west- and east-dipping veins. A third deformation event (Dl) produced by NE–SW shortening is related to the late barren hydrothermal quartz vein formation. Mineralogically, the veins are filled with abundant quartz, and scarce tourmaline and feldspars. Alteration halos composed of neoformed tourmaline and plagioclase within a talc and white mica matrix developed specifically during the late Dl event. A model of regional deformation giving rise to large-scale folds and quartz vein formation formed in response to E–W and NE–SW directions of shortening globally is proposed and discussed in this paper. [ABSTRACT FROM AUTHOR]

Although the concept of theranostics is neither new nor exclusive to nuclear medicine, it is a particularly promising approach for the future of nuclear oncology. This approach is based on the use of molecules targeting specific biomarkers in the tumour or its microenvironment, associated with optimal radionuclides which, depending on their emission properties, allow the combination of diagnosis by molecular imaging and targeted radionuclide therapy (TRT). Copper-64 has suitable decay properties (both β+ and β- decays) for PET imaging and potentially for TRT, making it both an imaging and therapy agent. We developed and evaluated a theranostic approach using a copper-64 radiolabelled anti-CD138 antibody, [64Cu]Cu-TE1PA-9E7.4 in a MOPC315.BM mouse model of multiple myeloma. PET imaging using [64Cu]Cu-TE1PA-9E7.4 allows for high-resolution PET images. Dosimetric estimation from ex vivo biodistribution data revealed acceptable delivered doses to healthy organs and tissues, and a very encouraging tumour absorbed dose for TRT applications. Therapeutic efficacy resulting in delayed tumour growth and increased survival without inducing major or irreversible toxicity has been observed with 2 doses of 35 MBq administered at a 2-week interval. Repeated injections of [64Cu]Cu-TE1PA-9E7.4 are safe and can be effective for TRT application in this syngeneic preclinical model of MM. [ABSTRACT FROM AUTHOR]

The Passa Três granite is a 5 km2 intrusion in southern Brazil with an NNE–SSW-elongated shape, hosting gold-bearing quartz veins with fluorite, carbonates, sulphides (pyrite, chalcopyrite, aikinite, molybdenite) and native gold. Orebodies are hosted by the pluton roof zone, which is marked by various textures indicating magmatic–hydrothermal transition processes. Mineralisation formed between 613 and 608 Ma in extensional pull-apart structures controlled by two conjugated N–S and E–W fault systems. We report results from petrography, quantitative evaluation of minerals by scanning electron microscopy (QEMSCAN), scanning electron microscopy (SEM), electron probe microanalyses (EPMA), X-ray fluorescence (XRF), trace element analyses of pyrite by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), sulphur isotope (δ34S) analyses, and fluid inclusion microthermometry. Hydrothermal alteration is dominantly developed as phengite–quartz–carbonate and sericite–carbonate–chlorite assemblages along mineralised structures. Fluid inclusion study indicates mineralising fluids with H2O-CO2-NaCl composition, low to moderate salinity (0.2–12.84 wt % NaCl eq.), and temperatures from 400 to 150 °C. The sulphur isotopic composition of pyrite (−0.1 to 1.1‰) suggests magmatic origin. These data, in conjunction with structurally controlled mineralisation enriched in Au-Bi minerals shortly post-dating the granite emplacement, appoint towards similarities between the Passa Três deposit and intrusion-related gold systems. The specific location of the mineralisation in the core (and in the roof zone, regarding its vertical position) of the Passa Três granitic intrusion defines it as "granite-hosted" thus, it is representative of a specific model that can be used for exploration of other intrusion-related/hosted gold deposits near the studied area or in other locations. [ABSTRACT FROM AUTHOR]

Recent advances in molecular characterization of tumors have allowed identification of new molecular targets on tumor cells or biomarkers. In medical practice, the identification of these biomarkers slowly but surely becomes a prerequisite before any treatment decision, leading to the concept of personalized medicine. Immuno-positron emission tomography (PET) fits perfectly with this approach. Indeed, monoclonal antibodies (mAbs) labelled with radionuclides represent promising probes for theranostic approaches, offering a non-invasive solution to assess in vivo target expression and distribution. Immuno-PET can potentially provide useful information for patient risk stratification, diagnosis, selection of targeted therapies, evaluation of response to therapy, prediction of adverse effects or for titrating doses for radioimmunotherapy. This paper reviews some aspects and recent developments in labelling methods, biological targets, and clinical data of some novel PET radiopharmaceuticals. [ABSTRACT FROM AUTHOR]

This paper reviews some aspects and recent developments in the use of antibodies to target radionuclides for tumor imaging and therapy. While radiolabeled antibodies have been considered for many years in this context, only a few have reached the level of routine clinical use. However, alternative radionuclides, with more appropriate physical properties, such as lutetium-177 or copper-67, as well as alpha-emitting radionuclides, including astatine-211, bismuth-213, actinium-225, and others are currently reviving hopes in cancer treatments, both in hematological diseases and solid tumors. At the same time, PET imaging, with short-lived radionuclides, such as gallium-68, fluorine-18 or copper-64, or long half-life ones, particularly iodine-124 and zirconium-89 now offers new perspectives in immuno-specific phenotype tumor imaging. New antibody analogues and pretargeting strategies have also considerably improved the performances of tumor immunotargeting and completely renewed the interest in these approaches for imaging and therapy by providing theranostics, companion diagnostics and news tools to make personalized medicine a reality. [ABSTRACT FROM AUTHOR]

Simple Summary: The prevalence of TEM-1 in the vasculature and the stroma of solid tumors and in malignant cells of sarcomas suggests that targeting TEM-1 could have therapeutic benefit. In this context, an anti-TEM-1 companion diagnostic may assist in the personalized medicine approach, whereby TEM-1 expression is exploited as a biomarker to select patients that would most benefit from a treatment directed toward the TEM-1 antigen. In our previous works, we have selected 1C1m-Fc, a fusion protein antibody, radiolabeled it with 177Lu and demonstrated that [177Lu]Lu-1C1m-Fc has interesting therapeutic performance. To define a suitable radiopharmaceutical companion for theranostic applications, 64Cu was chosen to radiolabel the fusion protein antibody. The aim of this work was thus to determine if [64Cu]Cu-1C1m-Fc can be considered for TEM-1 PET imaging and to predict the dosimetry of the [177Lu]Lu-1C1m-Fc companion therapy. 1C1m-Fc, a promising anti-TEM-1 DOTA conjugate, was labeled with 64Cu to target cancer cells for PET imaging and predicting the efficacy and safety of a previously studied [177Lu]Lu-1C1m-Fc companion therapy. DOTA-conjugated 1C1m-Fc was characterized by mass spectrometry, thin layer chromatography and immunoreactivity assessment. PET/CT and biodistribution studies were performed in human neuroblastoma xenografted mice. Absorbed doses were assessed from biodistribution results and extrapolated to 177Lu based on the [64Cu]Cu-1C1m-Fc data. The immunoreactivity was ≥ 70% after 48 h of incubation in serum, and the specificity of [64Cu]Cu-1C1m-Fc for the target was validated. High-resolution PET/CT images were obtained, with the best tumor-to-organ ratios reached at 24 or 48 h and correlated with results of the biodistribution study. Healthy organs receiving the highest doses were the liver, the kidneys and the uterus. [64Cu]Cu-1C1m-Fc could be of interest to give an indication of 177Lu dosimetry for parenchymal organs. In the uterus and the tumor, characterized by specific TEM-1 expression, the 177Lu-extrapolated absorbed doses are overestimated because of the lack of later measurement time points. Nevertheless, 1C1m-Fc radiolabeled with 64Cu for imaging would appear as an interesting radionuclide companion for therapeutic application with [177Lu]Lu-1C1m-Fc. [ABSTRACT FROM AUTHOR]

1C1m-Fc, an anti-tumor endothelial marker 1 (TEM-1) scFv-Fc fusion protein antibody, was previously successfully radiolabeled with 177Lu. TEM-1 specific tumor uptake was observed together with a non-saturation dependent liver uptake that could be related to the number of dodecane tetraacetic acid (DOTA) chelator per 1C1m-Fc. The objective of this study was to verify this hypothesis and to find the best DOTA per 1C1m-Fc ratio for theranostic applications. 1C1m-Fc was conjugated with six concentrations of DOTA. High-pressure liquid chromatography, mass spectrometry, immunoreactivity assessment, and biodistribution studies in mice bearing TEM-1 positive tumors were performed. A multi-compartment pharmacokinetic model was used to fit the data and a global pharmacokinetic model was developed to illustrate the effect of liver capture and immunoreactivity loss. Organ absorbed doses in mice were calculated from biodistribution results. A loss of immunoreactivity was observed with the highest DOTA per 1C1m-Fc ratio. Except for the spleen and bone, an increase of DOTA per 1C1m-Fc ratio resulted in an increase of liver uptake and absorbed dose and a decrease of uptake in tumor and other tissues. Pharmacokinetic models correlated these results. The number of DOTA per antibody played a determining role in tumor targeting. One DOTA per 1C1m-Fc gave the best pharmacokinetic behavior for a future translation of [177Lu]Lu-1C1m-Fc in patients. [ABSTRACT FROM AUTHOR]

Although positron emission tomography (PET) imaging with 18-Fluorodeoxyglucose (18F-FDG) is a promising technique in multiple myeloma (MM), the development of other radiopharmaceuticals seems relevant. CD138 is currently used as a standard marker for the identification of myeloma cells and could be used in phenotype tumor imaging. In this study, we used an anti-CD138 murine antibody (9E7.4) radiolabeled with copper-64 (64Cu) or zirconium-89 (89Zr) and compared them in a syngeneic mouse model to select the optimal tracers for MM PET imaging. Then, 9E7.4 was conjugated to TE2A-benzyl isothiocyanate (TE2A) and desferrioxamine (DFO) chelators for 64Cu and 89Zr labeling, respectively. 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 antibodies were evaluated by PET imaging and biodistribution studies in C57BL/KaLwRij mice bearing either 5T33-MM subcutaneous tumors or bone lesions and were compared to 18F-FDG-PET imaging. In biodistribution and PET studies, 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 displayed comparable good tumor uptake of subcutaneous tumors. On the bone lesions, PET imaging with 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 showed higher uptake than with 18F-FDG-PET. Comparison of both 9E7.4 conjugates revealed higher nonspecific bone uptakes of 89Zr-DFO-9E7.4 than 64Cu-TE2A-9E7.4. Because of free 89Zr's tropism for bone when using 89Zr-anti-CD138, 64Cu-anti-CD138 antibody had the most optimal tumor-to-nontarget tissue ratios for translation into humans as a specific new imaging radiopharmaceutical agent in MM. [ABSTRACT FROM AUTHOR]

The major role played by pre-existing structures in the formation of vein-style mineral deposits is demonstrated with several examples. The control of a pre-existing decollement level on the formation of a crustal extension-related (collapse) gold deposit is first illustrated in the Quadrilátero Ferrífero from Brazil. Shear zone and decollement structures were also examined and shown to control veins formation by three distinct processes: (i) re-aperture and re-using of wrench shear zones in the case of Shila gold mines (south Peru); (ii) remobilisation of metal in volcanic-hosted massive sulphide (VHMS) deposit by subsequent tectonic events and formation of a secondary stockwork controlled by structures created during this event (Iberian Pyrite Belt, Spain); (iii) formation of economic stockwork by contrasting deformation behaviours between ductile black schist versus brittle more competent dolomite (Cu-Ifri deposit, Morocco). Two examples involve changing of rheological competence within zones affected by deformation and/or alteration in order to receive the mineralisation (case studies of Achmmach, Morocco, and Mina Soriana, Spain). The last case underscores the significance of the magmatic–hydrothermal transition in the formation of mesothermal gold deposits (Bruès mine, Spain). All these examples clearly demonstrate the crucial role played by previously formed structures and/or texture in the development and formation of ore deposits. [ABSTRACT FROM AUTHOR]

The Jbel Saghro is interpreted as part of a long-lived silicic large igneous province. The area comprises two lithostructural complexes. The Lower Complex consists of folded metagreywackes and N070–090°E dextral shear zones, which roughly results from a NW–SE to NNW–SSE shortening direction related to a D1 transpressive tectonic stage. D1 is also combined with syntectonic plutons emplaced between ca. 615 and 575 Ma. The Upper Complex is defined by ash-flow caldera emplacements, thick and widespread ignimbrites, lavas and volcaniclastic sedimentary rocks with related intrusives that were emplaced in three main magmatic flare ups at ca. 575, 565 and 555 Ma. It lies unconformably on the Lower Complex units and was affected by a D2 trantensive tectonic stage. Between 550 and 540 Ma, the magmatic activity became slightly alkaline and of lower extent. Ore deposits show specific features, but remain controlled by the same structural setting: a NNW–SSE shortening direction related to both D1 and D2 stages. Porphyry Au(–Cu–Mo) and intrusion-related gold deposits were emplaced in an earlier stage between 580 and 565 Ma. Intermediate sulfidation epithermal deposits may have been emplaced during lull periods after the second and (or) the third flare-ups (560–550 Ma). Low sulfidation epithermal deposits were emplaced late during the felsic alkaline magmatic stage (550–520 Ma). The D2 stage, therefore, provided extensional structures that enabled fluid circulations and magmatic-hydrothermal ore forming processes. [ABSTRACT FROM AUTHOR]

Pb-Zn deposits and specifically Sedimentary-Exhalative (SEDEX) deposits are frequently found in deformed and/or metamorphosed geological terranes. Ore bodies structure is generally difficult to observe and its relationships to the regional structural framework is often lacking. In the Pyrenean Axial Zone (PAZ), the main Pb-Zn mineralizations are commonly considered as Ordovician SEDEX deposits in the literature. New structural field analyzes focusing on the relations between mineralization and regional structures allowed us to classify these Pb-Zn mineralizations into three types: (I) Type 1 corresponds to minor disseminated mineralization, probably syngenetic and from an exhalative source. (II) Type 2a is a stratabound mineralization, epigenetic and synchronous to the Variscan D1 regional deformation event and (III) Type 2b is a vein mineralization, epigenetic and synchronous to the late Variscan D2 regional deformation event. Structural control appears to be a key parameter in concentrating Pb-Zn in the PAZ, as mineralizations occur associated to fold hinges, cleavage, and/or faults. Here we show that the main exploited type 2a and type 2b Pb-Zn mineralizations are intimately controlled by Variscan tectonics. This study demonstrates the predominant role of structural study for unraveling the formation of Pb-Zn deposits especially in deformed/metamorphosed terranes. [ABSTRACT FROM AUTHOR]

Although positron emission tomography (PET) imaging with 18-Fluorodeoxyglucose ( 18 F-FDG) is a promising technique in multiple myeloma (MM), the development of other radiopharmaceuticals seems relevant. CD138 is currently used as a standard marker for the identification of myeloma cells and could be used in phenotype tumor imaging. In this study, we used an anti-CD138 murine antibody (9E7.4) radiolabeled with copper-64 ( 64 Cu) or zirconium-89 ( 89 Zr) and compared them in a syngeneic mouse model to select the optimal tracers for MM PET imaging. Then, 9E7.4 was conjugated to TE2A-benzyl isothiocyanate (TE2A) and desferrioxamine (DFO) chelators for 64 Cu and 89 Zr labeling, respectively. 64 Cu-TE2A-9E7.4 and 89 Zr-DFO-9E7.4 antibodies were evaluated by PET imaging and biodistribution studies in C57BL/KaLwRij mice bearing either 5T33-MM subcutaneous tumors or bone lesions and were compared to 18 F-FDG-PET imaging. In biodistribution and PET studies, 64 Cu-TE2A-9E7.4 and 89 Zr-DFO-9E7.4 displayed comparable good tumor uptake of subcutaneous tumors. On the bone lesions, PET imaging with 64 Cu-TE2A-9E7.4 and 89 Zr-DFO-9E7.4 showed higher uptake than with 18 F-FDG-PET. Comparison of both 9E7.4 conjugates revealed higher nonspecific bone uptakes of 89 Zr-DFO-9E7.4 than 64 Cu-TE2A-9E7.4. Because of free 89 Zr's tropism for bone when using 89 Zr-anti-CD138, 64 Cu-anti-CD138 antibody had the most optimal tumor-to-nontarget tissue ratios for translation into humans as a specific new imaging radiopharmaceutical agent in MM.

Recent advances in molecular characterization of tumors have allowed identification of new molecular targets on tumor cells or biomarkers. In medical practice, the identification of these biomarkers slowly but surely becomes a prerequisite before any treatment decision, leading to the concept of personalized medicine. Immuno-positron emission tomography (PET) fits perfectly with this approach. Indeed, monoclonal antibodies (mAbs) labelled with radionuclides represent promising probes for theranostic approaches, offering a non-invasive solution to assess in vivo target expression and distribution. Immuno-PET can potentially provide useful information for patient risk stratification, diagnosis, selection of targeted therapies, evaluation of response to therapy, prediction of adverse effects or for titrating doses for radioimmunotherapy. This paper reviews some aspects and recent developments in labelling methods, biological targets, and clinical data of some novel PET radiopharmaceuticals., Competing Interests: The authors declare no conflict of interest.