Kinsey, C. G. et al. Protective autophagy elicited by RAF→MEK→ERK inhibition suggests a treatment strategy for RAS-driven cancers. Nature Medicine 1 (2019). doi:10.1038/s41591-019-0367-9

These researchers discovered a combination drug therapy that may effectively combat the pancreatic cancer disease. The mixing of two drugs typically associated with malaria and melanoma target proteins activated by KRAS, the most commonly mutated protein in pancreatic cancer. KRAS itself is often considered "undruggable," because previous efforts to therapeutically block it directly have been unsuccessful. Given the compelling preclinical data acquired on mice with nanoScan PETMRI1T and SPECTCT, compassionate treatment of one patient was successfully initiated.

Pereira, R. et al. Mapping Aldehyde Dehydrogenase 1A1 Activity using an [18F]Substrate-Based Approach. Chemistry – A European Journal 25, 2345–2351 (2019)

Imaging the cancer stem cell marker ALDH1A1. Aldehyde dehydrogenases (ALDHs) catalyze the oxidation of aldehydes to carboxylic acids. Elevated ALDH expression in human cancers is linked to metastases and poor overall survival. Presented in this report are the synthesis and biological evaluation of ALDH1A1-selective chemical probes. [18F]4-b was taken up by colorectal tumor cells and trapped. In vivo PET  revealed high uptake of [18F]4-b in the lungs and liver, with radioactivity cleared through the urinary tract. Oxidation of [18F]4-b, however, was observed in vivo, which may limit the tissue penetration of this first-in-class radiotracer. Imaging performed on nanoScan PET/CT at Centre for Advanced Biomedical Imaging, University College London, London, UK.

Tucker, E. W. et al. Noninvasive 11C-rifampin positron emission tomography reveals drug biodistribution in tuberculous meningitis. Science Translational Medicine 10, eaau0965 (2018).

Tuberculous meningitis (TBM) is a devastating form of tuberculosis (TB), and key TB antimicrobials, including rif­ampin, have restricted brain penetration. Multidrug treatment was performed in rabbits with experimentally induced Tuberculous meningitis and and serial noninvasive dynamic 11C-rifampin positron emission tomography (PET) imaging was performed over 6 weeks. Rifampin penetration into infected brain lesions was limited, spatially heterogeneous, and decreases rapidly as early as 2 weeks into treatment. Moreover, rifampin concentrations in the cerebrospinal fluid did not correlate well with those in the brain lesions. The collected data demonstrate the proof of concept of PET as a clinically translatable tool to noninvasively measure intralesional antimicrobial distribution in infected tissues. Imaging performed on nanoScan PET/CT at Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD.

Nielsen, K. M. et al. Preclinical evaluation of potential infection-imaging probe [68Ga]Ga-DOTA-K-A9 in sterile and infectious inflammation. Journal of Labelled Compounds and Radiopharmaceuticals 61, 780–795 (2018).  PubMed

The development of bacteria-specific infection radiotracers is of considerable interest to improve diagnostic accuracy and enabling therapy monitoring. The aim of this study was to determine if the (DOTA) conjugated peptide [68Ga]Ga-DOTA-K-A9 could detect a staphylococcal infection in vivo and distinguish it from aseptic inflammation. The in vivo infection binding specificity of [68Ga]Ga-DOTA-K-A9 was evaluated by nanoScan PET/MRI imaging of 15 mice. The tracer was not found to be selective towards infection, since it also accumulated in mice with inflammation. Thus, the [68Ga]Ga-DOTA-K-A9 uptake observed in vivo is presumably a combination of local hyperemia, vascular leakiness and/or binding to an epitope present in dead bacteria.

Frisch, K. et al. N-(4-[18F]fluorobenzyl)cholylglycine, a novel tracer for PET of enterohepatic circulation of bile acids: Radiosynthesis and proof-of-concept studies in rats. Nuclear Medicine and Biology 61, 56–62 (2018).  PubMed

Enterohepatic circulation (EHC) of conjugated bile acids is an important physiological process crucial for regulation of intracellular concentrations of bile acids and their function as detergents and signal carriers. Authors have developed a radiosynthesis of a novel fluorine-18 labeled bile acid derivative, [18F]FBCGly, and shown by PET/MR that [18F]FBCGly undergoes continuous EHC in rats without metabolizing. This novel tracer may prove useful in PET studies on the effect of drugs or diseases on the EHC of conjugated bile acids.

  Chan, X. H. D. et al. Multimodal Imaging Approach to Monitor Browning of Adipose Tissue In Vivo. J. Lipid Res. jlr.D083410 (2018). doi:10.1194/jlr.D083410

Authors expressed near-IF fluorescent protein, iRFP720, in mice by viral transduction, and used multispectral optoacoustic imaging technology with ultrasound tomography (MSOT-US) to assess adipose beiging during adrenergic stimulation. Approach was validated against hybrid PET/MRI imaging by MRI-guided segmentation of 2-deoxy-2-18F-fluoro-d-glucose PET uptake signals. The browning extent detected by MSOT-US and PET/MR are well correlated with Ucp1 induction.

Bertelsen, F. et al. Acute in vivo effect of valproic acid on the GABAergic system in rat brain: A [11C]Ro15-4513 microPET study. Brain Research 1680, 110–114 (2018). PubMed

The BZD ligand, Ro15-4513 can be used to investigate the GABA shift in the brains of living rats after VPA exposure. A baseline 90-min dynamic [11C]Ro15-4513 PET scan was acquired with nanoScan PET/MRI1T prior to an intravenous injection of VPA, and was followed by a second [11C]Ro15-4513 PET scan. Authors showed a significant increase in [11C]Ro15-4513 uptake in hippocampus and amygdala, but no significant differences in cerebellar uptake, after acute VPA exposure. In contrast to several in vitro studies, the authors demonstrated a positive allosteric change in the GABAA receptors after pharmacologically enhanced GABA levels resulting in enhanced Ro15-4513 uptake.

Provost, J. et al. Simultaneous positron emission tomography and ultrafast ultrasound for hybrid molecular, anatomical and functional imaging. Nature Biomedical Engineering 2, 85–94 (2018)

The authors designed and built a pre-clinical scanner that registers PET–CT and UUI volumes acquired simultaneously and offers multiple combinations for imaging. PET–CT–UUI allows for simultaneous images of the vasculature and metabolism during tumour growth in mice and rats, as well as for synchronized multi-modal cardiac cine-loops. The researchers used commercially avaliable products: a pre-clinical PET/CT, the nanoScan PET/CT from Mediso and a clinical UUI device.

Webb, R. L. et al. Human Neural Stem Cell Extracellular Vesicles Improve Tissue and Functional Recovery in the Murine Thromboembolic Stroke Model. Transl. Stroke Res. 1–10 (2017) PubMed

Extracellular vesicles (EVs), nanometer-sized cell signaling particles, were tested in a mouse thromboembolic (TE) stroke model. Neural stem cell (NSC) and mesenchymal stem cell (MSC) EVs were evaluated. In-111 labeled EVs were injected and animals were imaged at 1h and 24h post-injection. Based on the clearance of the infarct, animals received a treatment of either EVs or PBS and later evaluated. NSC EV Treatment reduced lesion volume and improved behavioral outcomes in aged mice.

Sarabia-Estrada, R. et al. Effects of primary and recurrent sacral chordoma on the motor and nociceptive function of hindlimbs in rats: an orthotopic spine model. Journal of Neurosurgery: Spine 27, 215–226 (2017). PubMed

Chordoma is a slow-growing, locally aggressive cancer that is minimally responsive to conventional chemotherapy and radiotherapy and has high local recurrence rates after resection. Authors developed the first spine rodent model of human chordoma and used various imaging techniques, including MRI, CBCT, and nanoScan PET/CT to follow rats 550 days.

 Thompson, J. M. et al. Oral-Only Linezolid-Rifampin Is Highly Effective Compared with Other Antibiotics for Periprosthetic Joint Infection: Study of a Mouse Model. JBJS 99, 656 (2017). PubMed

Good CT reconstruction of prosthetic implants in mouse femurs. The medical treatment of periprosthetic joint infection (PJI) involves prolonged systemic antibiotic courses. Oral and intravenous monotherapies and combination antibiotic regimens were evaluated in a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) PJI.

Dalm, S. U. et al. SSTR-Mediated Imaging in Breast Cancer: Is There a Role for Radiolabeled Somatostatin Receptor Antagonists? J Nucl Med 58, 1609–1614 (2017).

The application of a somatostatin receptor antagonist may increase the importance of somatostatin receptor (SSTR) mediated imaging and treatment of breast cancer (BC) patients. Findings were supported by in vivo SPECT/MRI and biodistribution studies after injection with 177Lu-DOTA-Tyr3-octreotate (SST agonist) or 177Lu-DOTA-JR11 (SSTR antagonist). significantly higher binding (up to 57 times higher) was measured of 111In-DOTA-JR11 than of 111In-DOTA-Tyr3-octreotate to the BC specimens in patient-derived xenograft orthotopic breast tumor mouse model.

Busk, M. et al. FDG-PET reproducibility in tumor-bearing mice: comparing a traditional SUV approach with a tumor-to-brain tissue ratio approach. Acta Oncologica 0, 1–10 (2017) PubMed

Tumor FDG retention normalized to brain signal (T/B) improved scan reproducibility and was superior to traditional SUV quantification in i.v. tracer-injected animals)

Liu, X. et al. Radiolabeled novel mAb 4G1 for immunoSPECT imaging of EGFRvIII expression in preclinical glioblastoma xenografts. Oncotarget 8, 6364–6375 (2016).

Development of novel anti-EGFRvIII monoclonal antibody 4G1 and ImmunoSPECT/CT imaging of 125I-4G1 in epidermal growth factor receptor mutant III (EGFRvIII) positive/negative tumor-bearing mice (nS SPECT/CT at Peking University, Beijing, China)

Ziegler, M. et al. Highly Sensitive Detection of Minimal Cardiac Ischemia using Positron Emission Tomography Imaging of Activated Platelets. Scientific Reports 6, 38161 (2016).

Diagnosis of minimal cardiac ischemia with non-invasive molecular PET imaging of activated platelets using newly generated scFv_{anti-GPIIb/IIIa}-⁶⁴CuMeCOSar radiotracer (nS PET/CT at Monash University, Australia)

Edmonds, S. et al. Exploiting the Metal-Chelating Properties of the Drug Cargo for In Vivo Positron Emission Tomography Imaging of Liposomal Nanomedicines. ACS Nano (2016). doi:10.1021/acsnano.6b05935 PubMed

Tracking liposomal drugs using PET imaging with ⁸⁹Zr-PLA in a model of metastatic breast and ovarian cancer (nS PET/CT at King's College, London, UK).

Irkle, A. et al. Identifying active vascular microcalcification by 18F-sodium fluoride positron emission tomography. Nature Communications 6, 7495 (2015).

A radioactive agent developed in the 1960s to detect bone cancer can be re-purposed to highlight the build-up of unstable calcium deposits in arteries, a process that can cause heart attack and stroke (nS PET/CT at University of Cambridge, UK).

Sander, K. et al. Development of Fluorine-18 Labeled Metabolically Activated Tracers for Imaging of Drug Efflux Transporters with Positron Emission Tomography. J. Med. Chem. 58, 6058–6080 (2015).

Developed PET tracer showed excellent initial brain uptake and clean conversion to the desired metabolite. Results provide proof-of-concept for development of pro-drug tracers for imaging of P-gp/BCRP function in vivo (nS PET/CT at University College London, UK).

Mills, B. et al. [18F]FDG-6-P as a novel in vivo tool for imaging staphylococcal infections. EJNMMI Res 5, (2015).

Modified [18F]FDG by phosphorylation to [18F]FDG-6-P to facilitate specific update and accumulation by Staphylococcus aureus and at the site of known infection radiopharmaceutical levels were elevated compared with uninfected controls.

Fack, F. et al. Bevacizumab treatment induces metabolic adaptation toward anaerobic metabolism in glioblastomas. Acta Neuropathol 129, 115–131 (2015).

Glioma anti-angiogenic therapy effects gone astray (anaerobic metabolism induction) monitored by multiple means including nanoScan PET/CT of Mediso by the Norwegian Haukeland Hospital, Bergen University Bergen Norway