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Objectives: Metastases and primary malignancies are common in the liver. Local ablative applications such as transarterial chemoembolization (TACE), and transarterial radioembolization (TARE) provide minimally invasive and safe treatment in unresectable liver tumors. Early detection of response to treatment prevents unnecessary toxicity and cost in non-responder patients and provides an earlier use of other options that may be effective. This study aimed to identify the role of 18F-fluorothymidine (FLT) positron emission tomography/computed tomography (PET/CT) in the assessment of early response to TACE and TARE treatments in patients with unresectable primary and metastatic liver tumors. Methods: This single-center study included 63 patients who underwent 18F-FLT PET/CT for response evaluation after TACE and TARE. After excluding 20 patients whose data were missing 43 TARE-receiving patients were analyzed. The compatibility of change in semi-quantitative values obtained from the 18F-FLT PET/CT images with the treatment responses detected in 18F-fluorodeoxyglucose PET/CT, CT, and MR images and survival was evaluated. Results: There was no correlation between early metabolic, morphological response, and 18F-FLT uptake pattern, and change in standardized uptake values (SUV) which were ΔSUVmax, ΔSUVmean, ΔSUVpeak., ΔSUVmean, Δ SUVpeak values. There was no significant correlation between 18F-FLT uptake pattern, ΔSUVmax, ΔSUVmean, ΔSUVpeak, and overall survival, progression-free survival (PFS) for the target lobe PFS for the whole-body. The survival distributions for the patients with >30% change in ΔSUVmax and ΔSUVpeak values were statistically significantly longer than the patients with <30% change (p<0.009 and p<0.024, respectively). Conclusion: There was significant longer PFS for target liver lobe in patients with more than 30% decrease in 18F-FLT SUVmax and SUVpeak of the liver lesion in primary and metastatic unresectable liver tumors undergoing TARE. [ABSTRACT FROM AUTHOR]

Although 3′-deoxy-3′[(18)F]-fluorothymidine (FLT)-positron emission tomography (PET) has been utilized for tumor response assessment to neoadjuvant chemotherapy in soft tissue sarcomas, it has not been exploited for the assessment of early response to systematically targeted therapies. Herein, we investigated the 18F-FLT PET/CT kinetics in patients with sarcoma who received targeted therapies. Among 15 patients with sarcoma who underwent 18F-FLT PET/CT, 5 patients (33%) patients were imaged at three time points: At baseline and at 1−15 weeks (MDM2-inhibitor treatment), and 10 patients (67%) were imaged twice: At baseline and at 1−4 weeks (MDM2 inhibitor, n = 5; c-met inhibitor n = 5). The patients with sarcoma had a total of 18 identifiable tumors. Twelve of 15 patients (80%) demonstrated 18F-FLT concentrations changes early, i.e., at 1−4 weeks. Eight patients responded (53.3%), four patients progressed (26.7%) based on FLT change of more than 10% increase, and three patients (20%) demonstrated no change. 18F-FLT PET/CT may be used for early response imaging to molecularly targeted therapies in patients with sarcoma. Further larger studies in specific sarcoma sub-types are warranted.

Although 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) is a sensitive nuclear medicine modality, specificity for characterizing lung cancer is limited. Tumor proliferation and early response to molecularly targeted therapy could be visualized using 3′-deoxy-3′[(18)F]-fluorothymidine (18F-FLT) PET/CT. The superiority of 18F-FLT PET/CT over 18F-FDG PET/CT in early therapeutic monitoring has been well described in patients after chemotherapy, radiotherapy, and/or chemo/radiotherapy. In thispilot study, we explorethe use of 18F-FLT PET/CT as an early response evaluation modality in patients with lung cancerand provide specific case studies of patients with small cell lung cancer and non-small cell lung cancer who received novel targeted therapies. Early response for c-MET inhibitor was observed in four weeks and for MDM2 inhibitor in nine days.

18F-fluorodeoxyglucose (18F-FDG) positron emission tomography–computed tomography (PET/CT) is established for characterising indeterminate pulmonary nodules and staging lung cancer where there is curative intent. Whilst a sensitive technique, specificity for characterising lung cancer is limited. There is recognition that evaluation of other aspects of abnormal cancer biology in addition to glucose metabolism may be more helpful in characterising tumours and predicting response to novel targeted cancer therapeutics. Therefore, efforts have been made to develop and evaluate new radiopharmaceuticals in order to improve the sensitivity and specificity of PET imaging in lung cancer with regards to characterisation, treatment stratification and therapeutic monitoring. 18F-fluorothymidine (18F-FLT) is a marker of cellular proliferation. It shows a lower accumulation in tumours than 18F-FDG as it only accumulates in the cells that are in the S phase of growth and demonstrates a low sensitivity for nodal staging. Its main role is in evaluating treatment response. Methionine is an essential amino acid. 11C-methionine is more specific and sensitive than 18F-FDG in differentiating benign and malignant thoracic nodules. 18Ffluoromisonidazole (18F-FMISO) is used for imaging tumour hypoxia. Tumour response to treatment is significantly related to the level of tumour oxygenation. Angiogenesis is the process by which new blood vessels are formed in tumours and is involved in tumour growth and metastatic tumour spread and is a therapeutic target. Most clinical studies have focused on targeted integrin PET imaging of which αvβ3 integrin is the most extensively investigated. It is upregulated on activated endothelial cells in association with tumour angiogenesis. Neuroendocrine tumour tracers, particularly 68Ga-DOTA-peptides, have an established role in imaging of carcinoid tumours. Whilst most of these tracers have predominantly been used in the research environment, they offer exciting opportunities for improving staging, characterisation, stratification and response assessment in an era of increased personalised therapy in lung cancer. [ABSTRACT FROM AUTHOR]

Objectives: Metastases and primary malignancies are common in the liver. Local ablative applications such as transarterial chemoembolization (TACE), and transarterial radioembolization (TARE) provide minimally invasive and safe treatment in unresectable liver tumors. Early detection of response to treatment prevents unnecessary toxicity and cost in non-responder patients and provides an earlier use of other options that may be effective. This study aimed to identify the role of 18 F-fluorothymidine (FLT) positron emission tomography/computed tomography (PET/CT) in the assessment of early response to TACE and TARE treatments in patients with unresectable primary and metastatic liver tumors., Methods: This single-center study included 63 patients who underwent 18 F-FLT PET/CT for response evaluation after TACE and TARE. After excluding 20 patients whose data were missing 43 TARE-receiving patients were analyzed. The compatibility of change in semi-quantitative values obtained from the 18 F-FLT PET/CT images with the treatment responses detected in 18 F-fluorodeoxyglucose PET/CT, CT, and MR images and survival was evaluated., Results: There was no correlation between early metabolic, morphological response, and 18 F-FLT uptake pattern, and change in standardized uptake values (SUV) which were ΔSUV max , ΔSUV mean , ΔSUV peak ., ΔSUV mean , Δ SUV peak values. There was no significant correlation between 18 F-FLT uptake pattern, ΔSUV max , ΔSUV mean , ΔSUV peak , and overall survival, progression-free survival (PFS) for the target lobe PFS for the whole-body. The survival distributions for the patients with >30% change in Δ SUV max and ΔSUV peak values were statistically significantly longer than the patients with <30% change (p<0.009 and p<0.024, respectively)., Conclusion: There was significant longer PFS for target liver lobe in patients with more than 30% decrease in 18 F-FLT SUV max and SUV peak of the liver lesion in primary and metastatic unresectable liver tumors undergoing TARE., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2022 by Turkish Society of Nuclear Medicine | Molecular Imaging and Radionuclide Therapy published by Galenos Yayınevi.)

To compare the diagnostic efficacies of 18F-FLT and 18F-FDG PET/CT in non-small-cell lung cancer (NSCLC), focusing on the correlation between FLT and FDG tumour uptake and tumour cell proliferation as indicated by the cyclin D1 labelling index. A total of 31 patients with NSCLC underwent FLT and FDG PET/CT scanning followed by surgery. PET/CT images were compared with the pathology. Tumour cell proliferation was assessed by cyclin D1 immunohistochemistry. The sensitivities of FLT and FDG PET/CT for the primary lesion were 74% and 94%, respectively ( p=0.031). For N staging, 77% patients were correctly staged, 6% overstaged, 16% understaged by FLT, while the values for FDG were 77%, 16% and 6%, respectively. The sensitivity, specificity, accuracy, and positive predictive value with FLT for lymph nodes were 65%, 98%, 93% and 89%, respectively, and 85%, 84%, 84% and 52% with FDG ( p<0.01).Tumour SUV of FLT was significantly correlated with the cyclin D1 labelling index ( r=0.644; p<0.01), but the SUV of FDG was not significantly correlated ( r=0.293; p>0.05). In terms of N staging, FLT PET/CT resulted in understaging of more patients but overstaging of fewer patients, and for regional lymph nodes showed better specificity, accuracy and positive predictive value than FDG PET/CT in NSCLC. Tumour FLT uptake was correlated with tumour cell proliferation as indicated by the cyclin D1 labelling index, suggesting that further studies are needed to evaluate the use of FLT PET/CT for the assessment of therapy response to anticancer drugs. [ABSTRACT FROM AUTHOR]

Although 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) is a sensitive nuclear medicine modality, specificity for characterizing lung cancer is limited. Tumor proliferation and early response to molecularly targeted therapy could be visualized using 3′-deoxy-3′[(18)F]-fluorothymidine (18F-FLT) PET/CT. The superiority of 18F-FLT PET/CT over 18F-FDG PET/CT in early therapeutic monitoring has been well described in patients after chemotherapy, radiotherapy, and/or chemo/radiotherapy. In thispilot study, we explorethe use of 18F-FLT PET/CT as an early response evaluation modality in patients with lung cancerand provide specific case studies of patients with small cell lung cancer and non-small cell lung cancer who received novel targeted therapies. Early response for c-MET inhibitor was observed in four weeks and for MDM2 inhibitor in nine days. [ABSTRACT FROM AUTHOR]

Diagnosing relapse after radiotherapy for lung cancer is challenging. The specificity of both CT and 18 F-FDG PET/CT is low because of radiation-induced changes. 3'-deoxy-3'- 18 F-fluorothymidine ( 18 F-FLT) PET has previously demonstrated higher specificity for malignancy than 18 F-FDG PET. We investigated the value of 18 F-FLT PET/CT for diagnosing relapse in irradiated lung cancer. Methods: Patients suspected of relapse of lung cancer after definitive radiotherapy (conventional fractionated radiotherapy [cRT] or stereotactic body radiotherapy [SBRT]) were included. Sensitivity and specificity were analyzed both within the irradiated high-dose volume (HDV) and on a patient basis. Marginal differences and interobserver agreement were assessed. Results: Sixty-three patients who had received radiotherapy in 70 HDVs (34 cRT; 36 SBRT) were included. The specificity of 18 F-FLT PET/CT was higher than that of 18 F-FDG PET/CT (HDV, 96% [95% CI, 87-100] vs. 71% [95% CI, 57-83] [ P = 0.0039]; patient-based, 90% [95% CI, 73-98] vs. 55% [95% CI, 36-74] [ P = 0.0020]). The difference in specificity between 18 F-FLT PET/CT and 18 F-FDG PET/CT was higher after cRT than after SBRT. The sensitivity of 18 F-FLT PET/CT was lower than that of 18 F-FDG PET/CT (HDV, 69% [95% CI, 41-89] vs. 94% [95% CI, 70-100] [ P = 0.1250]; patient-based, 70% [95% CI, 51-84] vs. 94% [95% CI, 80-99] [ P = 0.0078]). Adding 18 F-FLT PET/CT when 18 F-FDG PET/CT was positive or inconclusive improved the diagnostic value compared with 18 F-FDG PET/CT alone. In cRT HDVs, the probability of malignancy increased from 67% for 18 F-FDG PET/CT alone to 100% when both tracers were positive. Conclusion: 18 F-FLT PET/CT adds diagnostic value to 18 F-FDG PET/CT in patients with suspected relapse. The diagnostic impact of 18 F-FLT PET/CT was highest after cRT. We suggest adding 18 F-FLT PET/CT when 18 F-FDG PET/CT is inconclusive or positive within the previously irradiated volume to improve diagnostic value in patients for whom histologic confirmation is not easily obtained., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Although 3'-deoxy-3'[(18)F]-fluorothymidine (FLT)- positron emission tomography (PET) has been utilized for tumor response assessment to neoadjuvant chemotherapy in soft tissue sarcomas, it has not been exploited for the assessment of early response to systematically targeted therapies. Herein, we investigated the 18 F-FLT PET/CT kinetics in patients with sarcoma who received targeted therapies. Among 15 patients with sarcoma who underwent 18 F-FLT PET/CT, 5 patients (33%) patients were imaged at three time points: At baseline and at 1-15 weeks ( MDM2- inhibitor treatment), and 10 patients (67%) were imaged twice: At baseline and at 1-4 weeks ( MDM2 inhibitor, n = 5 ; c-met inhibitor n = 5). The patients with sarcoma had a total of 18 identifiable tumors. Twelve of 15 patients (80%) demonstrated 18 F-FLT concentrations changes early, i.e., at 1-4 weeks. Eight patients responded (53.3%), four patients progressed (26.7%) based on FLT change of more than 10% increase, and three patients (20%) demonstrated no change. 18 F-FLT PET/CT may be used for early response imaging to molecularly targeted therapies in patients with sarcoma. Further larger studies in specific sarcoma sub-types are warranted., Competing Interests: K.K. reports no COI. V.S. reports the following conflicts of interest: Research funding/ Grant support for clinical trials: Roche/ Genentech, Novartis, Bayer, GlaxoSmithKline, Nanocarrier, Vegenics, Celgene, Northwest Biotherapeutics, Berghealth, Incyte, Fujifilm, Pharmamar, D3, Pfizer, Multivir, Amgen, Abbvie, Alfa-sigma, Agensys, Boston Biomedical, Idera Pharma, Inhibrx, Exelixis, Blueprint medicines, Loxo oncology, Medimmune, Altum, Dragonfly therapeutics, Takeda and, National Comprehensive Cancer Network, NCI-CTEP and UT MD Anderson Cancer Center, Turning point therapeutics, Boston Pharmaceuticals. Travel: Novartis, Pharmamar, ASCO, ESMO, Helsinn, Incyte. Consultancy/ Advisory board: Helsinn, LOXO Oncology/ Eli Lilly, R-Pharma US, INCYTE, QED pharma, Medimmune, Novartis.Other: Medscape.

Background: To determine the optimum conditions for diagnosis of nasopharyngeal carcinoma, we established VX2 rabbit model to delineate gross target volume (GTV) in different imaging methods. Methods: The orthotopic nasopharyngeal carcinoma (NPC) was established in sixteen New Zealand rabbits. After 7-days inoculation, the rabbits were examined by CT scanning and then sacrificed for pathological examination. To achieve the best delineation, different GTVs of CT, MRI, 18 F-FDG PET/CT, and 18 F-FLT PET/CT images were correlated with pathological GTV (GTVp). Results: We found 45% and 60% of the maximum standardized uptake value (SUV max ) as the optimal SUV threshold for the target volume of NPC in 18 F-FDG PET/CT and 18 F-FLT PET/CT images, respectively (GTV FDG45% and GTV FLT60% ). Moreover, the GTV MRI and GTV CT were significantly higher than the GTVp ( P ≤ 0.05), while the GTV FDG45% and especially GTV FLT60% were similar to the GTVp ( R = 0.892 and R = 0.902, respectively; P ≤ 0.001). Conclusions: Notably, the results suggested that 18 F-FLT PET/CT could reflect the tumor boundaries more accurately than 18 F-FDG PET/CT, MRI and CT, which makes 18 F-FLT PET-CT more advantageous for the clinical delineation of the target volume in NPC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Unlabelled: We present and test the use of multimodality imaging as a topological tool to map the amount of the body exposed to ionizing radiation and the location of exposure, which are important indicators of survival and recovery. To achieve our goal, PET/CT imaging with 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) was used to measure cellular proliferation in bone marrow (BM), whereas MRI using ultra-small superparamagnetic iron oxide (USPIO) particles provided noninvasive information on radiation-induced vascular damage., Methods: Animals were x-ray-irradiated at a dose of 7.5 Gy with 1 of 3 radiation schemes-whole-body irradiation, half-body shielding (HBS), or 1-leg shielding (1LS)-and imaged repeatedly. The spatial information from the CT scan was used to segment the region corresponding to BM from the PET scan using algorithms developed in-house, allowing for quantification of proliferating cells, and BM blood volume was estimated by measuring the changes in the T2 relaxation rates (ΔR2) collected from MR scans., Results: (18)F-FLT PET/CT imaging differentiated irradiated from unirradiated BM regions. Two days after irradiation, proliferation of 1LS animals was significantly lower than sham (P = 0.0001, femurs; P < 0.0001, tibias) and returned to sham levels by day 10 (P = 0.6344, femurs; P = 0.3962, tibias). The degree of shielding affected proliferation recovery, showing an increase in the irradiated BM of the femurs, but not the tibias, of HBS animals when compared with 1LS (P = 0.0310, femurs; P = 0.5832, tibias). MRI of irradiated spines detected radiation-induced BM vascular damage, measured by the significant increase in ΔR2 2 d after whole-body irradiation (P = 0.0022) and HBS (P = 0.0003) with a decreasing trend of values, returning to levels close to baseline over 10 d. Our data were corroborated using γ-counting and histopathology., Conclusion: We demonstrated that (18)F-FLT PET/CT and USPIO MRI are valuable tools in mapping regional radiation exposure and the effects of radiation on BM. Analysis of the (18)F-FLT signal allowed for a clear demarcation of exposed BM regions and elucidated the kinetics of BM recovery, whereas USPIO MRI was used to assess vascular damage and recovery., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)