Objective. To investigate the association between KRAS/NRAS/BRAF mutations and metabolic parameters of pretreatment 18F-FDG PET/CT in colorectal cancer (CRC). Methods. A total of 85 patients with CRC were included in the study. PET/CT was performed in all the patients before surgery. The histopathological examination and analysis of the gene mutational status of the primary tumor were conducted. The associations among clinical features, PET metabolic parameters, and the gene mutational status were investigated. Moreover, receiver operating characteristic (ROC) curves for maximum standard uptake value (SUVmax) of the primary tumor were generated along with analysis of the target tissue to nontarget tissue ratio (T/NT) for predicting the efficacy of KRAS/NRAS/BRAF mutations in CRC. Finally, the corresponding area under the curve, the optimal cutoff value, and the corresponding sensitivity and specificity were obtained. Results. The mutation rate of KRAS/NRAS/BRAF was 54.12% (46/85). In addition, both SUVmax and T/NT were significantly higher in the KRAS/NRAS/BRAF-mutation groups compared to the wild-type group (15.88 ± 6.71 vs. 12.59 ± 5.79, 8.04 ± 3.03 vs. 6.38 ± 2.80; P = 0.012 and 0.004, respectively). Results from the ROC curve also showed that the cutoff values for T/NT and SUVmax were 5.14 and 12.40, respectively, while the predictive accuracy was 0.682 and 0.647, respectively. On the other hand, the sensitivity was 91.30% and 65.22% while the specificity was 43.59% and 64.10%, respectively. Moreover, univariate analysis showed that the KRAS/NRAS/BRAF mutation was not significantly associated with gender, age, lesion location, tumor length, pathological type, tissue differentiation, and UICC staging (all P > 0.05 ). Conclusion. T/NT ratio and SUVmax could be the potential surrogate imaging indicators to predict the KRAS/NRAS/BRAF mutational status in CRC patients.

Purpose A series of radiotracers targeting fibroblast activation protein (FAP) with great pharmacokinetics have been developed for cancer diagnosis and therapy. Nevertheless, the use of dominant PET tracers, gallium-68–labeled FAPI derivatives, was limited by the short nuclide half-life and production scale, and the therapeutic tracers exhibited rapid clearance and insufficient tumor retention. In this study, we developed a FAP targeting ligand, LuFL, containing organosilicon-based fluoride acceptor (SiFA) and DOTAGA chelator, capable of labeling fluorine-18 and lutetium-177 in one molecular with simple and highly efficient labeling procedure, to achieve cancer theranostics. Methods The precursor LuFL (20) and [natLu]Lu-LuFL (21) were successfully synthesized and labeled with fluorine-18 and lutetium-177 using a simple procedure. A series of cellular assays were performed to characterize the binding affinity and FAP specificity. PET imaging, SPECT imaging, and biodistribution studies were conducted to evaluate pharmacokinetics in HT-1080-FAP tumor-bearing nude mice. A comparison study of [177Lu]Lu-LuFL ([177Lu]21) and [177Lu]Lu-FAPI-04 was carried out in HT-1080-FAP xenografts to determine the cancer therapeutic efficacy. Results LuFL (20) and [natLu]Lu-LuFL (21) demonstrated excellent binding affinity towards FAP (IC50: 2.29 ± 1.12 nM and 2.53 ± 1.87 nM), compared to that of FAPI-04 (IC50: 6.69 ± 0.88 nM). In vitro cellular studies showed that 18F-/177Lu-labeled 21 displayed high specific uptake and internalization in HT-1080-FAP cells. Micro-PET, SPECT imaging and biodistribution studies with [18F]/[177Lu]21 revealed higher tumor uptake and longer tumor retention than those of [68 Ga]/[177Lu]Ga/Lu-FAPI-04. The radionuclide therapy studies showed significantly greater inhibition of tumor growth for the [177Lu]21 group, than for the control group and the [177Lu]Lu-FAPI-04 group. Conclusion The novel FAPI-based radiotracer containing SiFA and DOTAGA was developed as a theranostics radiopharmaceutical with simple and short labeling process, and showed promising properties including higher cellular uptake, better FAP binding affinity, higher tumor uptake and prolong retention compared to FAPI-04. Preliminary experiments with 18F- and 177Lu-labeled 21 showed promising tumor imaging properties and favorable anti-tumor efficacy.

High-dose vitamin C (VC) exhibits anti-tumor effects, and the cytotoxicity of VC is correlated with oxidative stress. However, iron, as a redox metal, plays an important effect in redox cycling and free radical formation in cells. This study addresses the role of iron ion in the cytotoxicity of VC. We found that iron supplementation increases the anti-tumor effect of VC, which was influenced by the cellular iron uptake pathway–transferrin (TF)/transferrin receptor (TFR) system. The TFR expression of tumors can be assessed by 68Ga-citrate PET imaging, and it would be helpful to screen out the tumor type which is more sensitive to VC combined with an iron supplementation treatment.

No abstract