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- Altena, Renske, et al.
(författare)
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Human Epidermal Growth Factor Receptor 2 (HER2) PET Imaging of HER2-Low Breast Cancer with [ 68 Ga]Ga-ABY-025 : Results from a Pilot Study
- 2024
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine and Molecular Imaging. - 0161-5505 .- 1535-5667. ; 65:5, s. 700-707
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Tidskriftsartikel (refereegranskat)abstract
- Patients with HER2-low metastatic breast cancer (mBC), defined as an immunohistochemistry (IHC) score of 1+ or 2+ without HER2 gene amplification, may benefit from HER2 antibody-drug conjugates. Identifying suitable candidates is a clinical challenge because of spatial and temporal heterogeneity in HER2 expression and discrepancies in pathologic reporting. We aimed to investigate the feasibility and safety of HER2-specific PET imaging with [ 68 Ga]Ga-ABY-025 for visualization of HER2-low mBC.Methods: A prospective pilot study was done with 10 patients who had HER2-low mBC, as part of a phase 2 basket imaging study with [ 68 Ga]Ga-ABY-025 in HER2-expressing solid tumors. Patients were recruited at the Breast Clinic at the Karolinska University Hospital, Stockholm, Sweden. PET/CT images were acquired 3 h after injection of 200 MBq of [ 68 Ga]Ga-ABY-025. The SUV max was used to quantify tracer uptake. Ultrasound-guided tumor biopsies were guided by results from the HER2 PET. The main outcome-the safety and feasibility of HER2 PET in patients with HER2low mBC, measured the occurrence of possible procedure -related adverse events.Results: Ten patients with HER2-low mBC underwent [ 68 Ga]Ga-ABY-025 PET/CT with paired tumor biopsies. No adverse events occurred. In all patients, [ 68 Ga]Ga-ABY-025-avid lesions with substantial intra- and interindividual heterogeneity in tracer uptake were noted. In 8 of 10 patients with ABY-025-avid lesions, the HER2low status of the corresponding lesions was confirmed by IHC or in situ hybridization. Two patients had an IHC score of 0 in the tumor biopsies:1 in a cutaneous lesion with a low SUV max and 1 in a liver metastasis with a high SUV max but a "cold" core.Conclusion: The visualization of HER2-low mBC with [ 68 Ga]Ga-ABY-025 PET/CT was feasible and safe. Areas of tracer uptake showed varying levels of HER2 expression on IHC. The observed intra- and interindividual heterogeneity in [ 68 Ga]Ga-ABY-025 uptake suggested that HER2 PET might be used as a tool for the noninvasive assessment of disease heterogeneity and has the potential to identify patients in whom HER2-targeted drugs can have a clinical benefit.
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| 2. |
- Jussing, Emma
(författare)
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Development of radiometal-based labelling techniques and tracers for non-invasive molecular imaging
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Metallic radionuclides, radiometals, have an important role in nuclear medicine. Their straightforward coordination radiochemistry allows for a large variety of applications. The similarities and differences between the radiometals can be utilised to expand the window of diagnostic imaging or transfer diagnostic methods from one imaging modality to another. Radiometals from the same or from different elements (both therapeutic and diagnostic) may be coordinated to similar probes, as a theranostic pair. Radionuclide-based molecular imaging is a non-invasive in vivo imaging technique that quantifies the concentrations of radioactive probes in biological processes occurring at cellular and subcellular levels in living organisms. The two major diagnostic in vivo imaging techniques used are Single-Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET). In this thesis, radiometal production using a cyclotron solid target system and some fundamental aspects of radiometal labelling are explored, using two of the most common positron-emitting radiometals, gallium-68 (68Ga) and zirconium-89 (89Zr). In paper I an albumin targeting Affibody molecule, ABY-028, was successfully developed, 68Ga-labelled and in vivo evaluated using a small animal PET camera. We showed that the biodistribution was consistent with the binding of [68Ga]Ga-ABY-028 to plasma albumin. Uptake patterns differed between tumours at different stages and of different phenotypes. Tracer uptake responses to permeability-altering therapeutics and during cerebral infarction could be observed. This novel radiotracer is a promising tool for in vivo molecular imaging of variations and alterations of vascular permeability and has the potential to function as a baseline control of the non-specific uptake of other albumin-binding domain (ABD)-based diagnostic or therapeutic agents. In paper II cells were 89Zr-labelled, using two different metal complexes, with two distinctive labelling mechanisms, [89Zr]Zr-(oxine)4 and [89Zr]Zr-DFO-NCS. Synthesis protocols were successfully optimised to yield high radiochemical conversions of both 89Zr-complexes. Both radiotracers presented in this head-to-head study showed feasibility for universal radiolabellings of different cell types. The results suggested that [89Zr]Zr-(oxine)4 is most likely superior. In papers III and IV methods to meet the generally increasing demand for 68Ga have been developed. In paper III a cyclotron-based solid target system was used for production and purification of the radionuclide. In paper IV a refinement method of the radionuclide’s quality (regarding content of competing metal ions) was developed for clinical applicability for use in radiolabelling of DOTA-based radiopharmaceuticals, [68Ga]Ga-DOTATOC and [68Ga]Ga-FAPI-46. Compared to generator-derived 68Ga, we successfully produced 10 times more product of both the radiopharmaceuticals using our solid target cyclotron-produced 68Ga. The strategies and approaches investigated and developed in this thesis have potential for translation to more exotic radiometals in the future, to potentially expanding the palette of chemical properties that can be used in radiolabelling, as well as the decay characteristics and time-windows for imaging. The methods and techniques for radiometal labelling explored in this thesis might also be translated to other specific tissue targeting molecules or cell
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| 3. |
- Mallapura, Hemantha, et al.
(författare)
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Microfluidic-based production of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC using the cassette-based iMiDEVâ„¢ microfluidic radiosynthesizer
- 2023
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Ingår i: EJNMMI Radiopharmacy and Chemistry. - : Springer. - 2365-421X. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The demand for Ga-68-labeled radiotracers has significantly increased in the past decade, driven by the development of diversified imaging tracers, such as FAPI derivatives, PSMA-11, DOTA-TOC, and DOTA-TATE. These tracers have exhibited promising results in theranostic applications, fueling interest in exploring them for clinical use. Among these probes, Ga-68-labeled FAPI-46 and DOTA-TOC have emerged as key players due to their ability to diagnose a broad spectrum of cancers ([Ga-68]Ga-FAPI-46) in late-phase studies, whereas [Ga-68]Ga-DOTA-TOC is clinically approved for neuroendocrine tumors. To facilitate their production, we leveraged a microfluidic cassette-based iMiDEV radiosynthesizer, enabling the synthesis of [Ga-68]Ga-FAPI-46 and [Ga-68]Ga-DOTA-TOC based on a dose-on-demand (DOD) approach.Results Different mixing techniques were explored to influence radiochemical yield. We achieved decay-corrected yield of 44 +/- 5% for [Ga-68]Ga-FAPI-46 and 46 +/- 7% for [Ga-68]Ga-DOTA-TOC in approximately 30 min. The radiochemical purities (HPLC) of [Ga-68]Ga-FAPI-46 and [Ga-68]Ga-DOTA-TOC were 98.2 +/- 0.2% and 98.4 +/- 0.9%, respectively. All the quality control results complied with European Pharmacopoeia quality standards. We optimized various parameters, including Ga-68 trapping and elution, cassette batches, passive mixing in the reactor, and solid-phase extraction (SPE) purification and formulation. The developed synthesis method reduced the amount of precursor and other chemicals required for synthesis compared to conventional radiosynthesizers.Conclusions The microfluidic-based approach enabled the implementation of radiosynthesis of [Ga-68]Ga-FAPI-46 and [Ga-68]Ga-DOTA-TOC on the iMiDEV (TM) microfluidic module, paving the way for their use in preclinical and clinical applications. The microfluidic synthesis approach utilized 2-3 times less precursor than cassette-based conventional synthesis. The synthesis method was also successfully validated in a similar microfluidic iMiDEV module at a different research center for the synthesis of [Ga-68]Ga-FAPI-46 with limited runs. Our study demonstrated the potential of microfluidic methods for efficient and reliable radiometal-based radiopharmaceutical synthesis, contributing valuable insights for future advancements in this field and paving the way for routine clinical applications in the near future.
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