Bacterial cancer therapy (BCT) approaches have been extensively investigated because bacteria can show unique features of strong tropism for cancer, proliferation inside tumors, and antitumor immunity, while bacteria are also possible agents for drug delivery. Despite the rapidly increasing number of preclinical studies using BCT to overcome the limitations of conventional cancer treatments, very few BCT studies have advanced to clinical trials. In patients undergoing BCT, the precise localization and quantification of bacterial density in different body locations is important; however, most clinical trials have used subjective clinical signs and invasive sampling to confirm bacterial colonization. There is therefore a need to improve the visualization of bacterial densities using noninvasive and repetitive in vivo imaging techniques that can facilitate the clinical translation of BCT.In vivo optical imaging techniques using bioluminescence and fluorescence, which are extensively employed to image the therapeutic process of BCT in small animal research, are hard to apply to the human body because of their low penetrative power. Thus, new imaging techniques need to be developed for clinical trials. In this review, we provide an overview of the various in vivo bacteria-specific imaging techniques available for visualizing tumor-treating bacteria in BCT studies.

PURPOSE: Thyroglobulin (Tg) may be released from damaged residual thyroid tissues after radioactive iodine (RAI) therapy in patients with differentiated thyroid carcinoma (DTC). We investigated whether altered levels of serum Tg after recombinant human thyrotropin (rhTSH)-aided RAI therapy could be a prognostic marker in patients with DTC.METHODS: We evaluated 68 patients who underwent RAI therapy after total thyroidectomy. Serum Tg levels were measured just before RAI administration (D0Tg) and 7 days after RAI therapy (D7Tg). Patients with a D0Tg level greater than 2.0 ng/mL were excluded to more precisely evaluate the injury effect of RAI in small remnant tissues. The ratioTg was defined as the D7Tg level divided by that on D0Tg. The therapeutic responses were classified as acceptable or non-acceptable. Finally, we investigated which clinicopathologic parameters were associated with therapeutic response.RESULTS: At the follow-up examination, an acceptable response was observed in 50 patients (73.5%). Univariate analysis revealed significant differences in N stage (P = 0.003) and ratioTg (acceptable vs. non-acceptable responses, 21.9 ± 33.6 vs. 3.8 ± 6.5; P = 0.006). In multivariate analysis, only ratioTg significantly predicted an acceptable response (odds ratio 1.104; 95% confidence interval 1.005–1.213; P = 0.040). A ratioTg above 3.5 predicted an acceptable response with a sensitivity of 66.0%, specificity of 83.3%, and accuracy of 70.6% (area under the curve = 0.718; P = 0.006).CONCLUSIONS: Altered levels of serum Tg after RAI therapy, calculated as the ratioTg (D7Tg/D0Tg), significantly predicted an acceptable response in patients with DTC.
Follow-Up Studies ; Humans ; Iodine ; Multivariate Analysis ; Sensitivity and Specificity ; Thyroglobulin ; Thyroid Gland ; Thyroid Neoplasms ; Thyroidectomy ; Thyrotropin

PURPOSE: Thyroglobulin (Tg) may be released from damaged residual thyroid tissues after radioactive iodine (RAI) therapy in patients with differentiated thyroid carcinoma (DTC). We investigated whether altered levels of serum Tg after recombinant human thyrotropin (rhTSH)-aided RAI therapy could be a prognostic marker in patients with DTC. METHODS: We evaluated 68 patients who underwent RAI therapy after total thyroidectomy. Serum Tg levels were measured just before RAI administration (D0Tg) and 7 days after RAI therapy (D7Tg). Patients with a D0Tg level greater than 2.0 ng/mL were excluded to more precisely evaluate the injury effect of RAI in small remnant tissues. The ratioTg was defined as the D7Tg level divided by that on D0Tg. The therapeutic responses were classified as acceptable or non-acceptable. Finally, we investigated which clinicopathologic parameters were associated with therapeutic response. RESULTS: At the follow-up examination, an acceptable response was observed in 50 patients (73.5%). Univariate analysis revealed significant differences in N stage (P = 0.003) and ratioTg (acceptable vs. non-acceptable responses, 21.9 ± 33.6 vs. 3.8 ± 6.5; P = 0.006). In multivariate analysis, only ratioTg significantly predicted an acceptable response (odds ratio 1.104; 95% confidence interval 1.005–1.213; P = 0.040). A ratioTg above 3.5 predicted an acceptable response with a sensitivity of 66.0%, specificity of 83.3%, and accuracy of 70.6% (area under the curve = 0.718; P = 0.006). CONCLUSIONS Altered levels of serum Tg after RAI therapy, calculated as the ratioTg (D7Tg/D0Tg), significantly predicted an acceptable response in patients with DTC.

Purpose: We investigated the clinical role of F-18 fluorodeoxyglucose (FDG) positron emission tomography-computed tomography(PET-CT) in the identification of the primary site and the selection of the optimal biopsy site in patients with suspectedbone metastasis of unknown primary site. Methods: The patients with suspected bone metastasis who underwent PET-CT for evaluation of primary site were enrolled inthis study. The primary sites were identified by the histopathologic or imaging studies and were classified according to the FDGuptake positivity of the primary site. To evaluate the guiding capability of PET-CT in biopsy site selection, we statisticallyanalyzed whether the biopsy site could be affected according to the presence of extra-skeletal FDG uptake. Results: Among 74 enrolled patients, 51 patients had a metastatic bone disease. The primary site was identified in 48 of 51patients (94.1%). Forty-six patients were eligible to test the association of clinical choice of biopsy site with PET positivity ofextra-skeletal lesion. The extra-skeletal biopsies were done in 42 out of 43 patients with positive extra-skeletal uptake lesions.Bone biopsies were inevitably performed in the other three patients without extra-skeletal uptake lesions. The association cameout to be significant (Fisher’s exact test, P< 0.001). Conclusion F-18 FDG PET-CT significantly contributed not only to identify the primary site but also to suggest optimal biopsysites in patients with suspected bone metastasis.

Purpose: We investigated whether response classification after total thyroidectomy and radioactive iodine (RAI) therapy could be affected by serum levels of recombinant human thyrotropin (rhTSH)-stimulated thyroglobulin (Tg) measured at different time points in a follow-up of patients with papillary thyroid carcinoma (PTC). Methods: A total of 147 PTC patients underwent serum Tg measurement for response assessment 6 to 24 months after the first RAI therapy. Serum Tg levels were measured at 24 h (D1Tg) and 48–72 h (D2-3Tg) after the 2nd injection of rhTSH. Responses were classified into three categories based on serum Tg corresponding to the excellent response (ER-Tg), indeterminate response (IR-Tg), and biochemical incomplete response (BIR-Tg). The distribution pattern of response classification based on serum Tg at different time points (D1Tg vs. D2-3Tg) was compared. Results: Serum D2-3Tg level was higher than D1Tg level (0.339 ng/mL vs. 0.239 ng/mL, P < 0.001). The distribution of response categories was not significantly different between D1Tg-based and D2-3Tg-based classification. However, 8 of 103 (7.8%) patients and 3 of 40 (7.5%) patients initially categorized as ER-Tg and IR-Tg based on D1Tg, respectively, were reclassified to IR-Tg and BIR-Tg based on D2-3Tg, respectively. The optimal cutoff values of D1Tg for the change of response categories were 0.557 ng/mL (from ER-Tg to IR-Tg) and 6.845 ng/mL (from IR-Tg to BIR-Tg). Conclusion D1Tg measurement was sufficient to assess the therapeutic response in most patients with low level of D1Tg. Nevertheless, D2-3Tg measurement was still necessary in the patients with D1Tg higher than a certain level as response classification based on D2-3Tg could change.

Background/Aims: The prognostic significance of 18F-fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography (PET/CT) in peripheral T-cell lymphomas (PTCLs) are controversial. We explored the prognostic impact of sequential 18F-FDG PET/CT during frontline chemotherapy of patients with PTCLs. Methods: In total, 143 patients with newly diagnosed PTCLs were included. Sequential 18F-FDG PET/CTs were performed at the time of diagnosis, during chemotherapy, and at the end of chemotherapy. The baseline total metabolic tumor volume (TMTV) was calculated using the the standard uptake value with a threshold method of 2.5. Results: A baseline TMTV of 457.0 cm3 was used to categorize patients into high and low TMTV groups. Patients with a requirehigh TMTV had shorter progression-free survival (PFS) and overall survival (OS) than those with a low TMTV (PFS, 9.8 vs. 26.5 mo, p = 0.043; OS, 18.9 vs. 71.2 mo, p = 0.004). The interim 18F-FDG PET/CT response score was recorded as 1, 2–3, and 4–5 according to the Deauville criteria. The PFS and OS showed significant differences according to the interim 18F-FDG PET/CT response score (PFS, 120.7 vs. 34.1 vs. 5.1 mo, p < 0.001; OS, not reached vs. 61.1 mo vs. 12.1 mo, p < 0.001). Conclusions The interim PET/CT response based on visual assessment predicts disease progression and survival outcome in PTCLs. A high baseline TMTV is associated with a poor response to anthracycline-based chemotherapy in PTCLs. However, TMTV was not an independent predictor for PFS in the multivariate analysis.