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A quintessential setting for precision medicine, theranostics refers to a rapidly evolving field of medicine in which disease is diagnosed followed by treatment of disease-positive patients using tools for the therapy identical or similar to those used for the diagnosis. Against the backdrop of only-treat-when-visualized, the goal is a high therapeutic index with efficacy markedly surpassing toxicity. Oncology leads the way in theranostics innovation, where the approach has become possible with the identification of unique proteins and other factors selectively expressed in cancer versus healthy tissue, advances in imaging technology able to report these tissue factors, and major understanding of targeting chemicals and nanodevices together with methods to attach labels or warheads for imaging and therapy. Radiotheranostics-using radiopharmaceuticals-is becoming routine in patients with prostate cancer and neuroendocrine tumors who express the proteins PSMA (prostate-specific membrane antigen) and SSTR2 (somatostatin receptor 2), respectively, on their cancer. The palpable excitement in the field stems from the finding that a proportion of patients with large metastatic burden show complete and partial responses, and this outcome is catalyzing the search for more radiotheranostics approaches. Not every patient will benefit from radiotheranostics; but, for those who cross the target-detected line, the likelihood of response is very high.

Objective: To assess the test–retest reproducibility and intra/interobserver agreement of apparent diffusion coefficient (ADC) measurements of myeloma lesions using whole body diffusion-weighted MRI (WB-DW-MRI) at 3T MRI. Methods: Following ethical approval, 11 consenting patients with relapsed multiple myeloma were prospectively recruited and underwent baseline WB-DW-MRI. For a single bed position, axial DWI was repeated after a short interval to permit test–retest measurements. Mean ADC measurement was performed by two experienced observers. Intra- and interobserver agreement and test–retest reproducibility were assessed, using coefficient of variation (CV) and interclass correlation coefficient (ICC) measures, for diffuse and focal lesions (small ≤10 mm and large >10 mm). Results: 47 sites of disease were outlined (23 focal, 24 diffuse) in different bed positions (pelvis = 22, thorax = 20, head and neck = 5). For all lesions, there was excellent intraobserver agreement with ICC of 0.99 (0.98–0.99) and COV of 5%. For interobserver agreement, ICC was 0.89 (0.8–0.934) and COV was 17%. There was poor interobserver agreement for diffuse disease (ICC = 0.46) and small lesions (ICC = 0.54). For test–retest reproducibility, excellent ICC (0.916) and COV (14.5%) values for mean ADC measurements were observed. ICCs of test–retest were similar between focal lesions (0.83) and diffuse infiltration (0.80), while ICCs were higher in pelvic (0.95) compared to thoracic (0.81) region and in small (0.96) compared to large (0.8) lesions. Conclusion: ADC measurements of focal lesions in multiple myeloma are repeatable and reproducible, while there is more variation in ADC measurements of diffuse disease in patients with multiple myeloma. Advances in knowledge: Mean ADC measurements are repeatable and reproducible in focal lesions in multiple myeloma, while the ADC measurements of diffuse disease in multiple myeloma are more subject to variation. The evidence supports the future potential role of ADC measurements as predictive quantitative biomarker in multiple myeloma.

(18)F-Fluorodeoxyglucose positron emission tomography/CT imaging plays a key role in oncological imaging including in staging, radiotherapy planning, treatment response and recurrence assessment. Immunotherapies represent a major advance in cancer therapy for a number of tumours with resulting survival benefit. However, a wide range of immune related adverse events (irAEs), some of which can be apparent on imaging, have been reported. These involve many organ systems but particularly endocrine, cutaneous and gastrointestinal systems. Early detection of irAEs is essential to aid diagnosis and management of patients and to reduce associated morbidity. In addition, it is important to not mistake treatment related effects for disease. This pictorial review aims to identify common irAEs and changes seen on (18)F-fluorodeoxyglucose positron emission tomography/CT.

Background Fatty acids derived de novo or taken up from the extracellular space are an essential source of nutrient for cell growth and proliferation. Radiopharmaceuticals including 11C-acetate, and 18F-FAC (2-18F-fluoroacetate), have previously been used to study short-chain fatty acid (SCFA) metabolism. We developed 18F-fluoropivalate (18F-FPIA; 3-18F-fluoro-2,2-dimethylpropionic acid) bearing a gem-dimethyl substituent to assert metabolic stability for studying SCFA metabolism. We report the safety, biodistribution, and internal radiation dosimetry profile of 18F-FPIA in 24 healthy volunteers and the effect of dietary conditions. Materials and methods Healthy volunteer male and female subjects were enrolled (n = 24), and grouped into 12 fed and 12 fasted. Non-esterified fatty acids (NEFA) and carnitine blood measurements were assessed. Subjects received 159.48 MBq (range, 47.31–164.66 MBq) of 18F-FPIA. Radiochemical purity was > 99%. Safety data were obtained during and 24 h after radiotracer administration. Subjects underwent detailed multiple whole-body PET/CT scanning with sampling of venous bloods for radioactivity and radioactive metabolite quantification. Regions of interest were defined to derive individual and mean organ residence times; effective dose was calculated using OLINDA 1.1. Results All subjects tolerated 18F-FPIA with no adverse events. Over 90% of radiotracer was present in plasma at 60 min post-injection. The organs receiving highest absorbed dose (in mGy/MBq) were the liver (0.070 ± 0.023), kidneys (0.043 ± 0.013), gallbladder wall (0.026 ± 0.003), and urinary bladder (0.021 ± 0.004); otherwise there was low tissue uptake. The calculated effective dose using mean organ residence times over all 24 subjects was 0.0154 mSv/MBq (SD ± 0.0010). No differences in biodistribution or dosimetry were seen in fed and fasted subjects, though systemic NEFA and carnitine levels reflected fasted and fed states. Conclusion The favourable safety, imaging, and dosimetric profile makes 18F-FPIA a promising candidate radiotracer for tracing SCFA metabolism. Electronic supplementary material The online version of this article (10.1007/s00259-020-04724-y) contains supplementary material, which is available to authorized users.

Accurate disease monitoring is essential after transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) because of the potential for profound adverse events and large variations in survival outcome. Posttreatment changes on conventional imaging can confound determination of residual or recurrent disease, magnifying the clinical challenge. On the basis of increased expression of thymidylate synthase (TYMS), thymidine kinase 1 (TK-1), and equilibrative nucleoside transporter 1 (SLC29A1) in HCC compared with liver tissue, we conducted a proof-of-concept study evaluating the efficacy of 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) PET to assess response to TACE. Because previous PET studies in HCC have been hampered by high background liver signal, we investigated whether a temporal-intensity voxel clustering (kinetic spatial filtering, or KSF) improved lesion detection. Methods: A tissue microarray was built from 36 HCC samples and from matching surrounding cirrhotic tissue and was stained for TK-1. A prospective study was conducted; 18 patients with a diagnosis of HCC by the criteria of the American Association for the Study of Liver Diseases who were eligible for treatment with TACE were enrolled. The patients underwent baseline conventional imaging and dynamic 18F-FLT PET with KSF followed by TACE. Imaging was repeated 6–8 wk after TACE. The PET parameters were compared with modified enhancement-based RECIST. Results: Cancer Genome Atlas analysis revealed increased RNA expression of TYMS, TK-1, and SLC29A1 in HCC. TK-1 protein expression was significantly higher in HCC (P < 0.05). The sensitivity of 18F-FLT PET for baseline HCC detection was 73% (SUVmax, 9.7 ± 3.0; tumor to liver ratio, 1.2 ± 0.3). Application of KSF did not improve lesion detection. Lesion response after TACE by modified RECIST was 58% (14 patients with 24 lesions). A 30% reduction in mean 18F-FLT PET uptake was observed after TACE, correlating with an observed PET response of 60% (15/25). A significant and profound reduction in the radiotracer delivery parameter K1 after TACE was observed. Conclusion: 18F-FLT PET can differentiate HCC from surrounding cirrhotic tissue, with PET parameters correlating with TACE response. KSF did not improve visualization of tumor lesions. These findings warrant further investigation.

A 57-year-old woman with highly active relapsing-remitting multiple sclerosis (MS) treated with natalizumab developed dysarthria and right-sided hemiparesis. MRI demonstrated T2 hyperintensity (figure, A). CSF JC virus DNA titers were >1.1 M and progressive multifocal leukoencephalopathy (PML) was diagnosed. Natalizumab treatment was withdrawn.