Multidisciplinary management of patients with liver metastases (LM) requires a precision medicine approach, based on adequate profiling of tumor biology and robust biomarkers. Radiomics, defined as the high-throughput identification, analysis, and translational applications of radiological textural features, could fulfill this need. The present review aims to elucidate the contribution of radiomic analyses to the management of patients with LM. We performed a systematic review of the literature through the most relevant databases and web sources. English language original articles published before June 2020 and concerning radiomics of LM extracted from CT, MRI, or PET-CT were considered. Thirty-two papers were identified. Baseline higher entropy and lower homogeneity of LM were associated with better survival and higher chemotherapy response rates. A decrease in entropy and an increase in homogeneity after chemotherapy correlated with radiological tumor response. Entropy and homogeneity were also highly predictive of tumor regression grade. In comparison with RECIST criteria, radiomic features provided an earlier prediction of response to chemotherapy. Lastly, texture analyses could differentiate LM from other liver tumors. The commonest limitations of studies were small sample size, retrospective design, lack of validation datasets, and unavailability of univocal cut-off values of radiomic features. In conclusion, radiomics can potentially contribute to the precision medicine approach to patients with LM, but interdisciplinarity, standardization, and adequate software tools are needed to translate the anticipated potentialities into clinical practice.

Several studies highlighted the role of vascular ¹⁸F-NaF uptake as a marker of ongoing calcium deposition. However, ¹⁸F-NaF accumulation often shows inconsistent co-localization with arterial plaque. Actually, calcification activity and thus ¹⁸F-NaF uptake could prevail in the earlier plaque stages. To test this hypothesis, we evaluated¹⁸F-NaF uptake in three plaque types using plaque density as a marker of calcification progression. We also tested whether attenuation weighted image reconstruction affected ¹⁸F-NaF uptake values in the different plaque stages considered. Methods: 64 oncologic patients (14 males, mean age 65.3±8.2 range 26-81) underwent ¹⁸F-NaF PET/CT. A volume of interest (VOI), was drawn on each plaque within the infra-renal aorta, to assess mean SUV and attenuation value (HU). Plaques were then divided in light (LP, HU 510). SUV was normalized for blood ¹⁸F-NaF activity, to obtain plaque target-to background ratio (TBR). In this process, several focal, non-calcified ¹⁸F-NaF uptake areas were identified (hot spots, HS). TBR was computed in HS, after iso-contour thresholding. TBR was also calculated in a non-calcified control region (CR). In 35 patients, TBR was furthermore calculated on non-attenuation-corrected (NAC) images. Results: Among plaques, average TBR was highest in LP (2.21±0.88), while it was significantly lower in MP (1.59±0.53, p<0.001) and further decreased in HP (1.14±0.37, p<0.0001 with respect to both LP and MP). CR TBR was not significantly different to the one of HP and MP (P = ns), while it was significantly lower than LP and MP (p<0.01). HS had the highest absolute TBR (3.89±1.87, p<0.0001 vs LP). Considering TBR values originated from NAC didn’t provide significant difference from AC. Conclusion: The present study is in keeping with the concept that ¹⁸F-NaF is a feasible option in imaging molecular calcium deposition in the early stages of plaque formation, when active uptake mechanism are the main determinants of calcium presence while its retention progressively decreases with increasing calcium deposition in the arterial wall. From a technical point of view, our data suggest that NAC reconstruction doesn’t significantly affect output when evaluating plaques of any thickness. Methods: 64 oncologic patients (14 males, mean age 65.3±8.2 range 26-81) underwent ¹⁸F-NaF PET/CT. A volume of interest (VOI), was drawn on each plaque within the infra-renal aorta, to assess mean SUV and attenuation value (HU). Plaques were then divided in light (LP, HU 510). SUV was normalized for blood ¹⁸F-NaF activity, to obtain plaque target-to background ratio (TBR). In this process, several focal, non-calcified ¹⁸F-NaF uptake areas were identified (hot spots, HS). TBR was computed in HS, after iso-contour thresholding. TBR was also calculated in a non-calcified control region (CR). In 35 patients, TBR was furthermore calculated on non-attenuation-corrected (NAC) images. Results: Among plaques, average TBR was highest in LP (2.21±0.88), while it was significantly lower in MP (1.59±0.53, p<0.001) and further decreased in HP (1.14±0.37, p<0.0001 with respect to both LP and MP). CR TBR was not significantly different to the one of HP and MP (P = ns), while it was significantly lower than LP and MP (p<0.01). HS had the highest absolute TBR (3.89±1.87, p<0.0001 vs LP). Considering TBR values originated from NAC didn’t provide significant difference from AC. Conclusion: The present study is in keeping with the concept that ¹⁸F-NaF is a feasible option in imaging molecular calcium deposition in the early stages of plaque formation, when active uptake mechanism are the main determinants of calcium presence while its retention progressively decreases with increasing calcium deposition in the arterial wall. From a technical point of view, our data suggest that NAC reconstruction doesn’t significantly affect output when evaluating plaques of any thickness.

The present translational study aimed to verify whether serial ¹⁸F-FDG PET/CT predicts doxorubicin cardiotoxicity. Methods: Fifteen athymic mice were treated intravenously with saline (n = 5) or with 5 or 7.5 mg of doxorubicin per kilogram (n = 5 each) and underwent dynamic small-animal PET beforehand and afterward to estimate left ventricular (LV) metabolic rate of glucose (MRGlu). Thereafter, we retrospectively identified 69 patients who had been successfully treated with a regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine for Hodgkin disease (HD) and had undergone 4 consecutive ¹⁸F-FDG PET/CT scans. Volumes of interest were drawn on LV myocardium to quantify mean SUV. All patients were subsequently interviewed by telephone (median follow-up, 30 mo); 36 of them agreed to undergo electrocardiography and transthoracic echocardiography. Results: In mice, LV MRGlu was 17.9 ± 4.4 nmol × min⁻¹ × g⁻¹ at baseline. Doxorubicin selectively and dose-dependently increased this value in the standard-dose (27.9 ± 9 nmol × min⁻¹ × g⁻¹, P < 0.05 vs. controls) and high-dose subgroups (37.2 ± 7.8 nmol × min⁻¹ × g⁻¹, P < 0.01 vs. controls, P < 0.05 vs. standard-dose). In HD patients, LV SUV showed a progressive increase during doxorubicin treatment that persisted at follow-up. New-onset cardiac abnormalities appeared in 11 of 36 patients (31%). In these subjects, pretherapy LV SUV was markedly lower with respect to the remaining patients (1.53 ± 0.9 vs. 3.34 ± 2.54, respectively, P < 0.01). Multivariate analysis confirmed the predictive value of baseline LV SUV for subsequent cardiac abnormalities. Conclusion: Doxorubicin dose-dependently increases LV MRGlu, particularly in the presence of low baseline ¹⁸F-FDG uptake. These results imply that low myocardial ¹⁸F-FDG uptake before the initiation of doxorubicin chemotherapy in HD patients may predict the development of chemotherapy-induced cardiotoxicity, suggesting that prospective clinical trials are warranted to test this hypothesis.

In the course of metformin treatment, staging abdominal cancer lesions with ¹⁸F-FDG PET images is often hindered by the presence of a high bowel radioactivity. The present study aimed to verify the mechanism underlying this phenomenon. Methods: Fifty-three mice were submitted to dynamic acquisitions of ¹⁸F-FDG kinetics under fasting conditions. Three small-animal PET scans were obtained over a 4-mo study period. The animals were subdivided into 4 groups according to the following metformin administration protocol: group 1, untreated mice (n = 15); group 2, mice exposed to metformin treatment (750 mg/kg/d) for the 48 h before each PET study (pulsed, n = 10); group 3, mice treated for the whole study period (prolonged, n = 10); and group 4, mice in which prolonged treatment was interrupted 48 h before PET (interrupted, n = 8). The rate constant of ¹⁸F-FDG uptake was estimated by Patlak analysis. At the end of the study, the ileum and colon were harvested, washed, and counted ex vivo. Two further groups, of 5 animals each, were included to evaluate the effect of prolonged metformin treatment on phosphorylated adenosine monophosphate (AMP)–activated protein kinase (pAMPK) form and gene expression for thioredoxin-interacting protein (TXNIP). Results: Pulsed treatment did not modify gut tracer retention with respect to the untreated group. Conversely, prolonged treatment induced a progressive increase in ¹⁸F-FDG uptake that selectively involved the colonic wall, without any significant contamination of bowel content. This effect persisted after a complete drug washout in the interrupted group. These responses were paralleled by increased pAMPK availability and by reduced expression of TXNIP messenger RNA in colonic enterocytes exposed to prolonged metformin treatment. Conclusion: Metformin causes a selective increase in colonic ¹⁸F-FDG uptake. This effect appears after a relatively long period of treatment and persists soon after drug washout. Accordingly, the increased bowel glucose metabolism reflects a biologic response to chronic metformin treatment characterized by increased levels of pAMPK and reduced levels of TXNIP.