MILabs

𝗕𝗜𝗢𝗗𝗘𝗚𝗥𝗔𝗗𝗔𝗕𝗟𝗘 𝗧𝗜𝗦𝗦𝗨𝗘 𝗔𝗗𝗛𝗘𝗦𝗜𝗩𝗘 𝗙𝗢𝗥 𝗣𝗢𝗦𝗧-𝗘𝗫𝗧𝗥𝗔𝗖𝗧𝗜𝗢𝗡 𝗔𝗟𝗩𝗘𝗢𝗟𝗔𝗥 𝗕𝗢𝗡𝗘 𝗥𝗘𝗚𝗘𝗡𝗘𝗥𝗔𝗧𝗜𝗢𝗡 After tooth extraction in patients undergoing anticoagulation therapy, besides post-extraction bleeding, a very common complication is represented by pronounced alveolar bone resorption. The novel biodegradable polyurethane commercially available adhesive VIVO has shown a positive effect on soft tissue regeneration and hemostasis. However, the regenerative potential of VIVO in terms of bone regeneration has not yet been explored. The main aim of this study was to compare the post-extraction bone healing of a collagen sponge (COSP) and VIVO in the context of ongoing anticoagulation therapy. A #MILabs U-CT system was used for this 𝘪𝘯 𝘷𝘪𝘷𝘰 comparison in a rat model. Post-extraction bone analysis was conducted via 𝘪𝘯 𝘷𝘪𝘷𝘰 micro-computed tomography (U-CT), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX) after 5, 10, and 90 days. Looking at the study results, U-CT analysis revealed that VIVO and COSP led to significant increases in both bone volume and bone density. SEM images of the extraction sockets treated with either VIVO or COSP showed bone regeneration in the form of lamellar bone mass. Ratios of Ca/C and Ca/P observed via EDX indicated newly formed bone matrixes in both treatments after 90 days. There were no statistical differences between treatment with VIVO or COSP (gold standard). In conclusion, the hemostatic agents VIVO and COSP were both able to prevent pronounced bone loss, and both demonstrated a strong positive influence on the bone regeneration of the alveolar ridge post-extraction. Publication in International Journal of Molecular Sciences: https://lnkd.in/eQy5TDtW Used imaging platform: https://lnkd.in/eCJGR-uB #microCT #bone #regeneration #biodegradable #tissue_adhesives #tooth #makingmolecularimagingclear #invivo #rat #RWTH #preclinicalimaging

𝗚𝗮-𝟲𝟳-𝗟𝗔𝗕𝗘𝗟𝗘𝗗 𝗜𝗗𝗥-𝟭𝟬𝟬𝟮 𝗣𝗘𝗣𝗧𝗜𝗗𝗘 𝗖𝗢𝗠𝗣𝗥𝗘𝗛𝗘𝗡𝗦𝗜𝗩𝗘 𝗕𝗜𝗢𝗗𝗜𝗦𝗧𝗥𝗜𝗕𝗨𝗧𝗜𝗢𝗡 𝗔𝗦𝗦𝗘𝗦𝗦𝗠𝗘𝗡𝗧 Innate defense regulator-1002 (IDR-1002) is a synthetic peptide with promising immunomodulatory and antibiofilm properties. Although there is an appreciable body of work about its mechanism of action at the cellular and molecular level, along with its efficacy across several infection and inflammation models, little is known about its absorption, distribution, and excretion in live organisms. The main goal of this study was to perform a comprehensive biodistribution assessment with a gallium-67 radiolabeled derivative of IDR-1002 using nuclear tracing techniques. A #MILabs #VECTor system was used to perform all the SPECT/CT imaging. Various dose levels of the radiotracer (2–40 mg/kg) were administered into the blood, peritoneal cavity, and subcutaneous tissue, or instilled into the lungs. The results of this study proved that the peptide was well tolerated at all subcutaneous and intraperitoneal doses, although higher levels were associated with delayed absorption kinetics and precipitation of the peptide within the tissues. Low intratracheal doses were rapidly absorbed systemically, and small increases in the dose level were lethal. Intravenous doses were rapidly cleared from the blood at lower levels, and upon escalation, were toxic with a high proportion of the dose accumulating within the lung tissue. To improve biocompatibility and prolong its circulation within the blood, IDR-1002 was further formulated onto high molecular weight hyperbranched polyglycerol (HPG) polymers. Constructs prepared at 5:1 and 10:1 peptide-to-polymer ratios were colloidally stable, maintained the biological profile of the peptide payload and helped reduce red blood cell lysis. The 5:1 construct circulated well in the blood, but higher peptide loading was associated with rapid clearance by the reticuloendothelial system. In conclusion, many cationic peptides face pharmacokinetic and biocompatibility challenges, especially at high doses, but formulations such as those with HPG have the potential to overcome these limitations. Publication in Molecular Pharmaceutics: https://lnkd.in/e6W_U5uA Used imaging platform: https://lnkd.in/eCJGR-uB First author: Tullio V. F. Esposito #SPECT_CT #immunomodulation #IDR1002 #biodistribution #nuclear_tracing #makingmolecularimagingclear #invivo #mice #UBC #preclinicalimaging

𝗔 𝗡𝗔𝗡𝗢𝗘𝗠𝗨𝗟𝗦𝗜𝗢𝗡 𝗧𝗔𝗥𝗚𝗘𝗧𝗜𝗡𝗚 𝗔𝗗𝗜𝗣𝗢𝗦𝗘 𝗛𝗬𝗣𝗘𝗥𝗧𝗥𝗢𝗣𝗛𝗬 𝗔𝗡𝗗 𝗛𝗬𝗣𝗘𝗥𝗣𝗟𝗔𝗦𝗜𝗔 𝗧𝗢 𝗧𝗥𝗘𝗔𝗧 𝗢𝗕𝗘𝗦𝗜𝗧𝗬 Obesity often leads to severe medical complications, and existing FDA-approved medications to combat it have limited effectiveness in reducing adiposity and often cause side effects. Adipose tissue enlargement involves adipose hyperplasia and hypertrophy, both of which correlate with increased reactive oxygen species (ROS) and hyperactivated X-box binding protein 1 (XBP1) in (pre)adipocytes. The main aim of this study was to develop a biocompatible stress-remission nanoemulsion to co-inhibit XBP1 overactivation and excessive ROS by employing KIRA6 (XBP1 inhibitor) loaded α-Tocopherol nanoemulsion (KT-NE). A #MILabs U-CT system was used assess body fat distribution, and its alterations over time (3 weeks), in mice with obesity. The results of this study proved that that KT-NE simultaneously alleviates aberrant endoplasmic reticulum stress and oxidative stress in (pre)adipocytes. As a result, KT-NE significantly inhibits abnormal adipogenic differentiation, reduces lipid droplet accumulation, restricts lipid droplet transfer, impedes obesity progression, and lowers the risk of obesity-associated non-alcoholic fatty liver disease in female mice with obesity. In addition, diverse administration routes of KT-NE (i.v., i.p. and s.c.) impact its 𝘪𝘯 𝘷𝘪𝘷𝘰 biodistribution and contribute to localized and/or systemic anti-obesity effectiveness. Moreover, KT-NE could inhibit cascaded adipose hyperplasia and hypertrophy by restricting adipocyte interaction and blocking triglyceride biosynthesis 𝘪𝘯 𝘷𝘪𝘷𝘰 and 𝘪𝘯 𝘷𝘪𝘵𝘳𝘰. In conclusion, this study presents a strategy to alleviate the burden of obesity and reduce the risk of adiposity-related complications using a specific nano-platform (KT-NE). Overall, the therapeutic strategy proposed in this study might be a promising approach for the development of anti-obesity treatments. Publication in Nature Communications: https://lnkd.in/eCVk5Jbh Used imaging platform: https://lnkd.in/eCJGR-uB #microCT #obesity #adipose_tissue #visceral_fat #nanoemulsion #makingmolecularimagingclear #invivo #mice #ZJU #preclinicalimaging

𝗜𝗡𝗛𝗜𝗕𝗜𝗧𝗜𝗡𝗚 𝗧𝗔𝗧 𝗣𝗥𝗢𝗕𝗘 𝗕𝗜𝗡𝗗𝗜𝗡𝗚 𝗧𝗢 𝗔𝗟𝗕𝗨𝗠𝗜𝗡 𝗠𝗢𝗗𝗨𝗟𝗔𝗧𝗘𝗦 𝗜𝗧𝗦 𝗣𝗛𝗔𝗥𝗠𝗔𝗖𝗢𝗞𝗜𝗡𝗘𝗧𝗜𝗖𝗦 𝗔𝗡𝗗 𝗘𝗡𝗛𝗔𝗡𝗖𝗘𝗦 𝗜𝗧𝗦 𝗧𝗛𝗘𝗥𝗔𝗣𝗘𝗨𝗧𝗜𝗖 𝗘𝗙𝗙𝗘𝗖𝗧𝗦 Recently, (Ga-DOTA-K([²¹¹At]APBA)-c(RGDfK) ([²¹¹At]1)), a new probe for targeted alpha therapy (TAT) with albumin-binding moiety (ABM) was developed; it highly accumulated in tumors and significantly inhibited tumor growth in U-87 MG tumor-bearing mice. However, its high retention in blood may cause critical adverse events, such as hematotoxicity. For this reason, the main objective of this work was to find a way to accelerate the blood clearance of [²¹¹At]1 by competitively inhibiting the binding of [²¹¹At]1 to albumin to modulate the pharmacokinetics of the former. A #MILabs #VECTor system was used to investigate the biodistribution of [⁶⁷Ga]Ga-DOTA-K(IPBA)-c(RGDfK) ([⁶⁷Ga]2) with or without the administration of IPBA (4-(4-iodophenyl)-butyric acid, an albumin binding moiety) in U-87 MG tumor-bearing mice. The study results showed that blood radioactivity of [²¹¹At]1 was decreased in a dose-dependent manner with IPBA in normal mice. In U-87 MG tumor-bearing mice, the blood radioactivity and accumulation in nontarget tissues of [²¹¹At]1 were decreased by IPBA. Meanwhile, tumor [²¹¹At]1 accumulation was not changed at 3-h post-injection of IPBA. In SPECT/CT imaging of [⁶⁷Ga]2, IPBA administration dramatically decreased radioactivity in nontarget tissues, and only tumor tissue was visualized. In therapeutic experiments, [²¹¹At]1 with IPBA injected group significantly inhibited tumor growth compared to the control group. In conclusion, IPBA administration (as an albumin-binding inhibitor) could modulate the pharmacokinetics and enhance the therapeutic effects of [²¹¹At]1. Publication in European Journal of Nuclear Medicine and Molecular Imaging: https://lnkd.in/dzJrU7K3 Used imaging platform: https://lnkd.in/eCJGR-uB #SPECT_CT #Ga67 #At211 #targeted_alpha_therapy #theranostic #albumin_binding #makingmolecularimagingclear #invivo #mice #KanazawaUniv_O #preclinicalimaging

Meet us at 𝗣𝗵𝗮𝗿𝗺𝗮𝗟𝗮𝗯 𝗘𝘅𝗽𝗼 𝟮𝟬𝟮𝟰 @ Tokyo, an Asia's leading exhibition for drug discovery and pharma R&D technologies inside 𝗜𝗡𝗧𝗘𝗥𝗣𝗛𝗘𝗫 𝗪𝗲𝗲𝗸 𝗝𝗮𝗽𝗮𝗻, 𝗝𝘂𝗻𝗲 𝟮𝟲 - 𝟮𝟴, 𝟮𝟬𝟮𝟰, and discover our preclinical imaging solutions. #PET #SPECT #CT #optical #PharmaLab Expo 2024 #drug discovery #theranostics #oncology #preclinicalimaging #milabs #Tokyo

“It has been an exciting time to be part of #SNNMI24.   We were incredibly impressed by the advancements in preclinical (and clinical) imaging from #MILabs users and wider research communities.   We want to extend our gratitude to all the attendees who visited our booth and we are eagerly looking forward to our next meeting and hearing about the latest developments in your field of research.   Let's continue to push the boundaries of innovation together!   #preclinicalImaging #nuclearMedicine, #collimation #theranostics #theragnotics #radionuclidetherapy”

𝗙𝗟𝗔𝗦𝗛 𝗜𝗥𝗥𝗔𝗗𝗜𝗔𝗧𝗜𝗢𝗡 𝗣𝗥𝗘𝗦𝗘𝗡𝗧𝗦 𝗘𝗤𝗨𝗜𝗩𝗔𝗟𝗘𝗡𝗧 𝗖𝗔𝗣𝗔𝗕𝗜𝗟𝗜𝗧𝗬 𝗜𝗡 𝗠𝗢𝗗𝗨𝗟𝗔𝗧𝗜𝗡𝗚 𝗔𝗡𝗧𝗜𝗧𝗨𝗠𝗢𝗥 𝗜𝗠𝗠𝗨𝗡𝗘 𝗥𝗘𝗦𝗣𝗢𝗡𝗦𝗘 𝗔𝗦 𝗖𝗢𝗡𝗩𝗘𝗡𝗧𝗜𝗢𝗡𝗔𝗟 𝗗𝗢𝗦𝗘 𝗥𝗔𝗧𝗘 The capability of ultrahigh dose rate FLASH radiation therapy to generate the FLASH effect has opened the possibility to enhance the therapeutic index of radiation therapy. The contribution of the immune response has frequently been hypothesized to account for a certain fraction of the antitumor efficacy and tumor kill of FLASH but has yet to be rigorously evaluated. The main goal of this work was to investigate the immune response as a potentially important mechanism of the antitumor effect of FLASH using various murine tumor models grafted either subcutaneously or orthotopically into immunocompetent mice or in moderately and severely immunocompromised mice. FLASH (≥2000 Gy/s) was compared against the conventional (CONV) dose rate (0.1 Gy/s). A #MILabs U-CT system was used to image 𝘪𝘯 𝘷𝘪𝘷𝘰 mice, naïve and injected with SV2-OVA tumor cells, monitoring over time the tumor growth and healthy lung volume, which was segmented and reconstructed in 3D. The results of this study showed that FLASH and CONV 20 Gy were isoeffective in delaying tumor growth in immunocompetent and moderately immunodeficient hosts and increased tumor doubling time to >14 days versus >7 days in control animals. Interestingly, in profoundly immunocompromised mice, 20 Gy FLASH retained antitumor activity and significantly increased tumor doubling time to >14 days versus >8 days in control animals, suggesting a possible antitumor mechanism independent of the immune response. Furthermore, when a complete and long-lasting antitumor response was obtained (>140 days), both modalities of irradiation were able to generate a long-term immunologic memory response. In conclusion, the present results clearly document that the tumor responses across multiple immunocompetent and immunodeficient mouse models are largely dose rate independent and simultaneously contradict a major role of the immune response in the antitumor efficacy of FLASH. Therefore, this study indicates that FLASH is as potent as CONV in modulating antitumor immune response and can be used as an immunomodulatory agent. Publication in International Journal of Radiation Oncology*Biology*Physics: https://lnkd.in/e9ZWcNaU Used imaging platform: https://lnkd.in/eCJGR-uB First authors: Aymeric Almeida and Céline Godfroid #microCT #lung #tumor #FLASH #immunomodulation #makingmolecularimagingclear #invivo #mouse #CHUV #preclinicalimaging

𝗔𝗡 𝗜𝗠𝗣𝗥𝗢𝗩𝗘𝗗 𝗢𝗥𝗧𝗛𝗢𝗧𝗢𝗣𝗜𝗖 𝗟𝗘𝗙𝗧 𝗟𝗨𝗡𝗚 𝗧𝗥𝗔𝗡𝗦𝗣𝗟𝗔𝗡𝗧𝗔𝗧𝗜𝗢𝗡 𝗥𝗔𝗧 𝗠𝗢𝗗𝗘𝗟 Lung transplantation stands as the foremost recourse for numerous end-stage lung diseases. Despite a consistent annual rise in lung transplantations, the procedure still chases significantly behind other solid organ transplants like liver and kidney. The rat orthotopic left lung transplantation model, which closely mimics the procedural and pathophysiological dynamics of human lung transplantation, represents a pivotal instrument for elucidating the mechanisms and therapies pertinent to lung injury post-transplantation. Nonetheless, the widespread adoption of this model is hindered by the intricate surgical maneuvers involved and the prolonged learning curve it entails. The main goal of this work was to improve the rat orthotopic left lung transplantation model technique (using a modified three-cuff technique), refine nearly all facets of the model that may hinder researchers' understanding and meticulously described all key operational procedures. A #MILabs U-CT system was used to image 𝘪𝘯 𝘷𝘪𝘷𝘰 the transplanted left lung in rats one day, one month and six months after the surgery. Looking at the study results, the modified perfusion method here presented could prevent donor lung edema, while waist-shaped cuffs minimized suture slippage during anastomosis. Additionally, positioning the recipient rat in a slightly left-elevated supine position during anastomosis reduced tension on the lung hilum, thus mitigating the risk of vascular laceration. The introduction of a unique two-person anastomosis technique significantly reduced operation time and substantially improved success rates. Furthermore, maximizing inflation of donor lungs both during preservation and surgery minimized the occurrence of postoperative atelectasis. Various other procedural refinements contributed to the enhanced operability of this model. Sixty-four rat orthotopic left lung transplantations were performed with only one surgical failure observed. Even six months post-operation, transplanted left rat lungs continued to exhibit proper inflation and contraction rhythms, displaying signs of chronic pathological changes. In summary, this modified rat model of orthotopic left lung transplantation demonstrates robust operability, significantly reducing surgical duration, improving operation success rates, and enhancing postoperative survival rates. Furthermore, its long-term survival capacity enables the simulation of acute and chronic disease processes following lung transplantation. Publication in Heliyon: https://lnkd.in/edWuibRA Used imaging platform: https://lnkd.in/eCJGR-uB #microCT #lung #transplantation #surgery #anastomosis #cuffs #makingmolecularimagingclear #invivo #rat #ZJU #preclinicalimaging

¹⁵⁵Tb- & ¹⁶¹Tb- LABELED BIOCONGIUGATES AS THERANOSTIC PAIR FOR METASTATIC TUMORS TREATEMENT The incidence of melanoma have steadily increased over the last 50 years, outpacing almost all other types of cancer, and is the most lethal form of skin cancer, accounting for over 80 % of deaths from the disease. Traditional chemotherapy for advanced melanomas is generally ineffective, so the need for different treatment approaches is clear. Targeted radionuclide therapy is established as a highly effective strategy for the treatment of metastatic tumors; however, the co-development of suitable imaging companions to therapy remains significant challenge. The main goal of this work was to investigate a suitable theranostic pair (based on terbium theranostic isotopes), focusing mainly in finding suitable imaging companions to isotopes capable of targeted radionuclide therapy for the treatment of metastatic tumors. This work presents the first radiochemistry and preclinical studies involving ¹⁵⁵Tb- and ¹⁶¹Tb-labeled crown-αMSH, a small peptide-based bioconjugate suitable for targeting melanoma. A #MILabs #VECTor system was used to image these Tb-labeled bioconjugates in male C57Bl/6 J mice bearing B16-F10 melanoma tumors. Looking at the study results, radio-HPLC studies showed that [¹⁶¹Tb]Tb-crown-αMSH maintains excellent radiochemical purity in human serum, while gradual metabolic degradation is observed in mouse serum. Competitive binding assays showed the high affinity of [natTb]Tb-crown-αMSH toward melanocortin-1 receptor (MC1R). Preclinical in vivo studies of ¹⁵⁵Tb- and ¹⁶¹Tb- labeled crown-αMSH were performed in parallel, in mice bearing B16-F10 tumors; their biodistribution results showed similar tumor specific uptake and very low uptake in nontarget organs. These results were further corroborated through a series of SPECT-CT studies, with [¹⁵⁵Tb]Tb-crown-αMSH and [¹⁶¹Tb]Tb-crown-αMSH showing comparable uptake profiles and excellent image contrast. In conclusion, this work highlights the promising characteristics of [¹⁵⁵Tb]Tb-crown-αMSH and [¹⁶¹Tb]Tb-crown-αMSH as theranostic pair for nuclear imaging (¹⁵⁵Tb) and radionuclide therapy (¹⁶¹Tb). Publication in Nuclear Medicine and Biology:  https://lnkd.in/ejfErqqy Used imaging platform: https://lnkd.in/eCJGR-uB First author: Luke Wharton https://lnkd.in/ezi6ZgbD #SPECT_CT #theranostics #Tb¹⁵⁵ #Tb¹⁶¹ #melanoma #tumor #crown_chelator #makingmolecularimagingclear #invivo #mouse #UBC #preclinicalimaging

A successful installation of the MILabs PET/SPECT/CT imager at the prestigious MD Anderson Cancer Center in Houston, the #1 Oncology Hospital in the world.