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Position emission tomography (PET) is widely used in clinics and research due to its quantitative merits and high sensitivity, but suffers from low signal-to-noise ratio (SNR). Recently convolutional neural networks (CNNs) have been widely used to improve PET image quality. Though successful and efficient in local feature extraction, CNN cannot capture long-range dependencies well due to its limited receptive field. Global multi-head self-attention (MSA) is a popular approach to capture long-range information. However, the calculation of global MSA for 3D images has high computational costs. In this work, we proposed an efficient spatial and channel-wise encoder-decoder transformer, Spach Transformer, that can leverage spatial and channel information based on local and global MSAs. Experiments based on datasets of different PET tracers, i.e., 18F-FDG, 18F-ACBC, 18F-DCFPyL, and 68Ga-DOTATATE, were conducted to evaluate the proposed framework. Quantitative results show that the proposed Spach Transformer framework outperforms state-of-the-art deep learning architectures.

Urologic malignancies constitute a large portion of annually diagnosed cancers. Timely diagnosis, accurate staging, and assessment of tumor heterogeneity are essential to devising the best treatment strategy for individual patients. The high sensitivity of molecular imaging allows for early and sensitive detection of lesions that were not readily detectable using conventional imaging techniques. Moreover, molecular imaging enables the interrogation of molecular processes used in targeted cancer therapies and predicts cancer response to treatment. Here we review the current advancements in molecular imaging of urologic cancers, including prostatic, vesical, renal testicular, and ureteral cancers.

Background: When using botulinum toxin for the management of lateral epicondylitis, injection at a fixed distance from an anatomic landmark could result in inadequate paralysis of the intended muscle. We assessed the effectiveness of injection of botulinum toxin using precise anatomic measurement in individual patients. Methods: In this randomized placebo-controlled trial, 48 patients with chronic refractory lateral epicondylitis were randomly assigned to receive a single injection of either botulinum toxin (60 units) or placebo (normal saline). The site of injection was chosen as a distance one-third the length of the forearm from the tip of the lateral epicondyle on the course of the posterior interosseus nerve. The primary outcome measure was intensity of pain at rest, measured with the use of a 100-mm visual analogue scale, at baseline and at 4, 8 and 16 weeks after injection. Results: Compared with the placebo group, the group given botulinum toxin had significant reductions in pain at rest during follow-up (decrease at 4 weeks 14.1 mm, 95% confidence interval [CI] 5.8-22.3; at 8 weeks 11.5 mm, 95% CI 2.0-21.0; at 16 weeks 12.6 mm, 95% CI 7.7-17.8; p = 0.01). As for the secondary outcomes, the intensity of pain during maximum pinch decreased in the botulinum toxin group; there was no difference in pain during maximum grip or in grip strength between the two groups. All but one of the patients in the intervention group experienced weakness in the extension of the third and fourth fingers at week 4 that resolved by week 16. No serious adverse events were reported. Interpretation: The use of precise anatomic measurement to guide injection of botulinum toxin significantly reduced pain at rest in patients with chronic refractory lateral epicondylitis. However, the transient extensor lag makes this method inappropriate for patients whose job requires finger extension. (ClinicalTrials.gov trial register no. NCT00497913.), Botulinum toxin type A, a potent neuromuscular blocking agent, has been used for a variety of neuromuscular disorders, including cervical dystonia and blepharospasm. (1) Recently, this drug has been used [...]

Novel diagnostic and therapeutic radiopharmaceuticals are increasingly becoming a central part of personalized medicine. Continued innovation in the development of new radiopharmaceuticals is key to sustained growth and advancement of precision medicine. Artificial intelligence has been used in multiple fields of medicine to develop and validate better tools for patient diagnosis and therapy, including in radiopharmaceutical design. In this review, we first discuss common in silico approaches and focus on their usefulness and challenges in radiopharmaceutical development. Next, we discuss the practical applications of in silico modeling in design of radiopharmaceuticals in various diseases.

Hypoxia is associated with resistance to radiotherapy and chemotherapy. Functional imaging of hypoxia in non-small cell lung cancer (NSCLC) could allow early assessment of tumor response and guide subsequent therapies. Epidermal growth factor receptor (EGFR) inhibition with erlotinib reduces hypoxia in vivo. [18F]-Fluoromisonidazole (FMISO) is a radiolabeled tracer that selectively accumulates in hypoxic cells. We sought to determine whether FMISO positron emission tomography (FMISO-PET) could detect changes in hypoxia in vivoin response to EGFR-targeted therapy. In a preclinical investigation, nude mice with human EGFR-mutant lung adenocarcinoma xenografts underwent FMISO-PET scans before and 5 days after erlotinib or empty vehicle initiation. Descriptive statistics and analysis of variance (ANOVA) tests were used to analyze changes in standardized uptake value (SUV), with pooled analyses for the mice in each group (baseline, postvehicle, and posterlotinib). In a small correlative pilot human study, patients with EGFR-mutant metastatic NSCLC underwent FMISO-PET scans before and 10 to 12 days after erlotinib initiation. Changes in SUV were compared to standard chest computed tomography (CT) scans performed 6 weeks after erlotinib initiation. The mean (±standard error of the mean; SUVmean) of the xenografts was 0.17 ± 0.014, 0.14 ± 0.008, and 0.06 ± 0.004 for baseline, postvehicle, and posterlotinib groups, respectively, with lower SUVmean among the posterlotinib group compared to other groups (P< .05). Changes on preclinical PET imaging were striking, with near-complete disappearance of FMISO uptake after erlotinib initiation. Two patients were enrolled on the pilot study. In the first patient, SUVmean increased by 21% after erlotinib, with progression on 6-week chest CT followed by death after 4.8 months. In the second patient, SUVmean decreased by 7% after erlotinib, with regression on 6-week chest CT accompanied by clinical improvement; the patient had stable disease at 14.5 months. In conclusion, we observed that FMISO-PET can detect changes in hypoxia levels after EGFR-directed therapy in EGFR-mutant NSCLC. Further study is warranted to determine its utility as an imaging biomarker of early response to EGFR-directed therapy.

Therapeutically engineered stem cells (SC) are emerging as an effective tumor‐targeted approach for different cancer types. However, the assessment of the long‐term fate of therapeutic SC post‐tumor treatment is critical if such promising therapies are to be translated into clinical practice. In this study, we have developed an efficient SC‐based therapeutic strategy that simultaneously allows killing of tumor cells and assessment and eradication of SC after treatment of highly malignant glioblastoma multiforme (GBM). Mesenchymal stem cells (MSC) engineered to co‐express the prodrug converting enzyme, herpes simplex virus thymidine kinase (HSV‐TK) and a potent and secretable variant of tumor necrosis factor apoptosis‐inducing ligand (S‐TRAIL) induced caspase‐mediated GBM cell death and showed selective MSC sensitization to the prodrug ganciclovir (GCV). A significant decrease in tumor growth and a subsequent increase in survival were observed when mice bearing highly aggressive GBM were treated with MSC coexpressing S‐TRAIL and HSV‐TK. Furthermore, the systemic administration of GCV post‐tumor treatment selectively eliminated therapeutic MSC expressing HSV‐TK in vitro and in vivo, which was monitored in real time by positron emission‐computed tomography imaging using 18F‐FHBG, a substrate for HSV‐TK. These findings demonstrate the development and validation of a novel therapeutic strategy that has implications in translating SC‐based therapies in cancer patients. STEMCells2013;31:1706–1714

Esophageal cancer is the third most common malignancy of the alimentary tract. The incidence of esophageal cancer has steadily increased over the past three decades. Almost all therapeutic modalities for esophageal cancer are associated with a considerable mortality and morbidity. Consequently, there has been growing concern regarding effective management of esophageal cancer. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) is playing an increasing role in the management of esophageal cancer, offering potential advantages in the accuracy of disease assessment at a number of decision points in the management pathway. This review evaluates the critical role of FDG-PET in (i) diagnosis, (ii) preoperative staging, (iii) monitoring of response to neoadjuvant therapy, (iv) assessment of recurrence and (v) prediction of prognosis of esophageal cancer. We have also compared diagnostic performance of FDG-PET and other current technologies such as computed tomography scan and endoscopic ultrasonography based on available evidence.