Effective anticancer therapy induces tumor cell death through apoptosis. Noninvasive monitoring of apoptosis during therapy may provide predictive outcome information and help tailor treatment. A caspase-3-specific imaging radiotracer, 18 F-, has been developed for use in PET studies. We report the safety, biodistribution, and internal radiation dosimetry profiles of 18 F-ICMT-11 in 8 healthy human volunteers. Methods: 18 F-ICMT-11 was intravenously administered as a bolus injection (mean 6 SD, 159 6 2.75 MBq; range, 154-161 MBq) to 8 healthy volunteers (4 men, 4 women). Whole-body (vertex to mid thigh) PET/CT scans were acquired at 6 time points, up to 4 h after tracer injection. Serial whole blood, plasma, and urine samples were collected for radioactivity measurement and radiotracer stability. In vivo 18 F activities were determined from quantitative analysis of the images, and time-activity curves were generated. The total numbers of disintegrations in each organ normalized to injected activity (residence times) were calculated as the area under the curve of the time-activity curve, normalized to injected activities and standard values of organ volumes. Dosimetry calculations were then performed using OLINDA/EXM 1.1. Results: Injection of 18 F-ICMT-11 was well tolerated in all subjects, with no serious tracer-related adverse events reported. The mean effective dose averaged over both men and women was estimated to be 0.025 6 0.004 mSv/MBq (men, 0.022 6 0.004 mSv/MBq; women, 0.027 6 0.004 mSv/MBq). The 5 organs receiving the highest absorbed dose (mGy/MBq), averaged over both men and women, were the gallbladder wall (0.59 6 0.44), small intestine (0.12 6 0.05), upper large intestinal wall (0.08 6 0.07), urinary bladder wall (0.08 6 0.02), and liver (0.07 6 0.01). Elimination was both renal and via the hepatobiliary system. Conclusion: 18 F-ICMT-11 is a safe PET tracer with a dosimetry profile comparable to other common 18 F PET tracers. These data support the further development of 18 F-ICMT-11 for clinical imaging of apoptosis.

Magnetic particle imaging (MPI) is a new imaging modality with the potential for high‐resolution imaging while retaining the noninvasive nature of other current modalities such as magnetic resonance imaging (MRI) and positron emission tomography (PET). It is able to track location and quantities of special superparamagnetic iron oxide nanoparticles without tracing any background signal. MPI utilizes the unique, intrinsic aspects of the nanoparticles: how they react in the presence of the magnetic field, and the subsequent turning off of the field. The current group of nanoparticles that are used in MPI are usually commercially available for MRI. Special MPI tracers are in development by many groups that utilize an iron‐oxide core encompassed by various coatings. These tracers would solve the current obstacles by altering the size and material of the nanoparticles to what is required by MPI. In this review, the theory behind and the development of these tracers are discussed. In addition, applications such as cell tracking, oncology imaging, neuroimaging, and vascular imaging, among others, stemming from the implementation of MPI into the standard are discussed.Level of Evidence: 5Technical Efficacy Stage: 3J. Magn. Reson. Imaging 2020;51:1659–1668.

Fibroepithelial lesions (FELs) are a heterogeneous group of tumours comprising fibroadenomas (FAs) and phyllodes tumours (PTs). Here we used a 16-gene panel that was previously discovered to be implicated in pathogenesis and progression, to characterise a large international cohort of FELs via targeted sequencing. The study comprised 303 (38%) FAs and 493 (62%) PTs which were contributed by the International Fibroepithelial Consortium. There were 659 (83%) Asian and 109 (14%) non-Asian FELs, while the ethnicity of the rest was unknown. Genetic aberrations were significantly associated with increasing grade of PTs, and were detected more in PTs than FAs for MED12, TERT promoter, RARA, FLNA, SETD2, TP53, RB1, EGFR, and IGF1R. Most borderline and malignant PTs possessed ≥ 2 mutations, while there were more cases of FAs with ≤ 1 mutation compared to PTs. FELs with MED12 mutations had significantly higher rates of TERT promoter, RARA, SETD2, EGFR, ERBB4, MAP3K1, and IGF1R aberrations. However, FELs with wild-type MED12 were more likely to express TP53 and PIK3CA mutations. There were no significant differences observed between the mutational profiles of recurrent FAs, FAs with a history of subsequent ipsilateral recurrence or contralateral occurrence, and FAs without a history of subsequent events. We identified recurrent mutations which were more frequent in PTs than FAs, with borderline and malignant PTs harbouring cancer driver gene and multiple mutations. This study affirms the role of a set of genes in FELs, including its potential utility in classification based on mutational profiles.Conflict of interest statement: PHT, BTT, and PT jointly hold patent applications for PCT/SG2015/050107 (Breast fibroadenoma susceptibility mutations and use thereof) and PCT/SG2015/050368 (Method and kit for pathologic grading of breast neoplasms). The other authors declare no competing interests.

nature reviews | clinical oncology volume 7 | marCH 2010 | 122 research highlights correction the role of Src-3 in human breast cancer Ondrej gojis, Bharath rudraraju, Mihir gudi, Katy hogben, sami sousha, charles r. coombes, susan cleator and carlo Palmieri

Background Granulomatous mastitis (GM) is an inflammatory breast disease of unknown aetiology. It poses diagnostic and therapeutic challenges with myriad forms of clinical presentation, varying results to treatments and propensity to recur. This study aims to look at clinical and treatment factors that predispose to recurrence of GM. Methods We performed a retrospective review of 113 patients in our unit with histologically proven GM from 2006 to 2016. Demographic, clinical, treatment and outcomes data were collected and analysed. Results Eighty‐nine patients were treated with antibiotics (78.8%), 79 (69.9%) with steroids and 23 (20.4%) patients underwent surgery. Twenty (17.7%) patients had recurrence. Patients who presented with inflammatory signs and symptoms had increased odds of having subsequent recurrence: skin changes (1.50), pain (2.00), fistula (4.39) and antibiotic treatment (6.65). Four patients (20%) with recurrence had positive bacterial cultures. All 4 grew Corynebacterium. Patients with Corynebacterium infection had a 2.64 times higher risk of recurrence. Surgery did not preclude recurrence. There was a 70% (7/10) penicillin resistance rate in our patients with positive cultures for Corynebacterium. Conclusion Initial presentation with inflammatory signs and symptoms may confer increased risk of recurrence, warranting closer monitoring. Corynebacterium infection may play a part as a causative factor and risk factor for recurrence. Non‐penicillin antibiotics should be considered as first‐line antibiotics for patients presenting with inflammatory changes. Further prospective studies with larger patient populations might reveal information on the aetiology of GM and result in the development of a more standardized and effective treatment regimen.