Mean Tumor-to-background Ratio Research Articles

18F−Prostate−Specific Membrane Antigen PET/CT imaging for potentially resectable pancreatic cancer (PANSCAN−2): a phase I/II study

BackgroundCurrent diagnostic imaging modalities have limited ability to differentiate between malignant and benign pancreaticobiliary disease, and lack accuracy in detecting lymph node metastases. 18F-Prostate-Specific Membrane Antigen (PSMA) PET/CT is an imaging modality used for staging of prostate cancer, but has incidentally also identified PSMA-avid pancreatic lesions, histologically characterized as pancreatic ductal adenocarcinoma (PDAC). This phase I/II study aimed to assess the feasibility of 18F-PSMA PET/CT to detect PDAC.MethodsSeventeen patients with clinically resectable PDAC underwent 18F-PSMA PET/CT prior to surgical resection. Images were analyzed both visually and (semi)quantitatively by deriving the maximum standardized uptake value (SUVmax) and tumor-to-background ratio (TBR). TBR was defined as the ratio between SUVmax of the primary tumor divided by SUVmax of the aortic blood pool. Finally, tracer uptake on PET was correlated to tissue expression of PSMA in surgical specimens.ResultsOut of 17 PSMA PET/CT scans, 13 scans demonstrated positive PSMA tracer uptake, with a mean SUVmax of 5.0 ± 1.3. The suspected primary tumor was detectable (TBR ≥ 2) with a mean TBR of 3.3 ± 1.3. For histologically confirmed PDAC, mean SUVmax and mean TBR were 4.9 ± 1.2 and 3.3 ± 1.5, respectively. Although eight patients had histologically confirmed regional lymph node metastases and two patients had distant metastases, none of these metastases demonstrated 18F-PSMA uptake. There was no correlation between 18F-PSMA PET/CT SUVmax and tissue expression of PSMA in surgical specimens.Conclusions18F-PSMA PET/CT was able to detect several pancreaticobiliary cancers, including PDAC. However, uptake was generally low, not specific to PDAC and no tracer uptake was observed in lymph node or distant metastases. The added value of PSMA PET in this setting appears to be limited.Trial registrationThe trial is registered as PANSCAN-2 in the European Clinical Trials Database (EudraCT number: 2020–002185-14).Graphical

Optical molecular imaging in oral- and oropharyngeal squamous cell carcinoma using a novel uPAR-targeting near-infrared imaging agent FG001 (ICG-Glu-Glu-AE105): An explorative phase II clinical trial.

Background: In oral and oropharyngeal squamous cell carcinoma (OSCC, OPSCC), frequent inadequate surgical margins highlight the importance of precise intraoperative identification and delineation of cancerous tissue for improving patient outcomes. Methods: A prospective, open-label, single-center, single dose, exploratory phase II clinical trial (EudraCT 2022-001361-12) to assess the efficacy of the novel uPAR-targeting near-infrared imaging agent, FG001, for intraoperative detection of OSCC and OPSCC. Macroscopic tumor detection was quantified with sensitivity and intraoperative tumor-to-background ratio (TBR). Microscopic tumor-specificity was assessed by analysis of morphological co-localization between tumor tissue, uPAR-expression, and optical signal. Blood samples were collected up to 44 hours post-injection to further characterize the pharmacokinetic profile of the agent. The trial was conducted with close safety monitoring. Results: Sixteen patients undergoing primary surgical resection were systemically administered 36 mg (n = 4), 16 mg (n = 8), or 4 mg (n = 4) of FG001 the evening prior to surgery. Intraoperatively, using a near-infrared imaging system, real-time optical imaging successfully identified all 16 tumors (sensitivity: 100%, mean TBR: 2.99 range: 2.02 - 3.95), and tumor-specificity was confirmed by histology. Clinical neck metastasis was detected with optical imaging. The maximal plasma concentrations were measured after 1 hour, and the half-life of FG001 was 12 hours. No drug-related or serious adverse events were observed. Conclusions: FG001 holds great potential for optical molecular imaging of OSCC and OPSCC. Further trials are warranted to explore FG001 for intraoperative margin delineation and as a decision-making tool.

18F] MFBG PET imaging: biodistribution, pharmacokinetics, and comparison with [123I] MIBG in neural crest tumour patients.

Despite its limitations, [123I]MIBG scintigraphy has been the standard for human norepinephrine transporter (hNET) imaging for several decades. Recently, [18F]MFBG has emerged as a promising PET alternative. This prospective trial aimed to evaluate safety, biodistribution, tumour lesion pharmacokinetics, and lesion targeting of [18F]MFBG and perform a head-to-head comparison with [123I]MIBG in neural crest tumour patients. Six neural crest tumour patients (4 phaeochromocytoma, 1 paraganglioma, 1 neuroblastoma) with a recent routine clinical [123I]MIBG scintigraphy (interval: - 37-75 days) were included. Adult patients (n = 5) underwent a 30-min dynamic PET, followed by 3 whole-body PET/CT scans at 60, 120, and 180 min after injection of 4 MBq/kg [18F]MFBG. One minor participant underwent a single whole-body PET/CT at 60 min after administration of 2 MBq/kg [18F]MFBG. Normal organ uptake (SUVmean) and lesion uptake (SUVmax; tumour-to-background ratio (TBR)) were measured. Regional distribution volumes (VT) were estimated using a Logan graphical analysis in up to 6 lesions per patient. A lesion-by-lesion analysis was performed to compare detection ratios (DR), i.e. fraction of detected lesions, between [18F]MFBG and [123I]MIBG. [18F]MFBG was safe and well tolerated. Its biodistribution was overall similar to that of [123I]MIBG, with prominent uptake in the salivary glands, liver, left ventricle wall and adrenals, and mainly urinary excretion. In the phaeochromocytoma subgroup, the median VT was 37.4 mL/cm3 (range: 18.0-144.8) with an excellent correlation between VT and SUVmean at all 3 time points (R2: 0.92-0.94). Mean lesion SUVmax and TBR at 1 h after injection were 19.3 ± 10.7 and 23.6 ± 8.4, respectively. All lesions detected with [123I]MIBG were also observed with [18F]MFBG. The mean DR with [123I]MIBG was significantly lower than with [18F]MFBG (61.0% ± 26.7% vs. 99.8% ± 0.5% at 1 h; p = 0.043). [18F]MFBG is a promising hNET imaging agent with favourable imaging characteristics and improved lesion targeting compared with [123I]MIBG scintigraphy. Clinicaltrials.gov : NCT04258592 (Registered: 06 February 2020), EudraCT: 2019-003872-37A.

Molecular imaging can identify the location to perform a frozen biopsy during intraoperative frozen section consultation.

BackgroundIntraoperative frozen section (FS) consultation is an important tool in surgical oncology that suffers from sampling error because the pathologist does not always know where to perform a biopsy of the surgical specimen. Intraoperative molecular imaging is a technology used in the OR to visualize lesions during surgery. We hypothesized that molecular imaging can address this pathology challenge in FS by visualizing the cancer cells in the specimen in the pathology suite. Here, we report the development and validation of a molecular-imaging capable cryostat called Smart-Cut.MethodsA molecular imaging capable cryostat prototype was developed and tested using a murine model. Tumors grown in mice were targeted with a NIR contrast agent, indocyanine green (ICG), via tail vein injection. Tumors and adjacent normal tissue samples were frozen sectioned with Smart-Cut. Fluorescent sections and non-fluorescent sections were prepared for H&E and fluorescent microscopy. Fluorescent signal was quantified by tumor-to-background ratio (TBR). NIR fluorescence was tested in one patient enrolled in a clinical trial.ResultsThe Smart-Cut prototype has a small footprint and fits well in the pathology suite. Fluorescence imaging with Smart-Cut identified cancerous tissue in the specimen in all 12 mice. No false positives or false negatives were seen, as confirmed by H&E. The mean TBR in Smart-Cut positive tissue sections was 6.8 (SD±3.8). In a clinical application in the pathology suite, NIR imaging identified two lesions in a pulmonary resection specimen, where traditional grossing only identified one.ConclusionMolecular imaging can be integrated into the pathology suite via the Smart-Cut device, and can detect cancer in frozen tissue sections using molecular imaging in a murine model.

Fluorophore-conjugated Helicobacter pylori recombinant membrane protein (HopQ) labels primary colon cancer and metastases in orthotopic mouse models by binding CEA-related cell adhesion molecules.

HopQ is an outer-membrane protein of Helicobacter pylori that binds to human carcinoembryonic antigen-related cell-adhesion molecules (CEACAMs) with high specificity. We aimed to investigate fluorescence targeting of CEACAM-expressing colorectal tumors in patient-derived orthotopic xenograft (PDOX) models with fluorescently labeled recombinant HopQ (rHopQ). Western blotting, flow cytometry and ELISA were performed to determine the efficiency of rHopQ binding to CEACAMs. rHopQ was conjugated to IR800DyeCW (rHopQ-IR800). Nude mice received orthotopic implantation of colon cancer tumors. Three weeks later, mice were administered 25 μg or 50 μg HopQ-IR800 and imaged 24 or 48 h later. Intravital images were analyzed for tumor-to-background ratio (TBR). Flow cytometry and ELISA demonstrated binding of HopQ to CEACAM1, 3 and 5. Dose-response intravital imaging in PDOX models demonstrated optimal results 48 h after administration of 50 μg rHopQ-IR800 (TBR = 3.576) in our protocol. Orthotopic models demonstrated clear tumor margins of primary tumors and small regional metastases with a mean TBR = 3.678 (SD ± 1.027). rHopQ showed specific binding to various CEACAMs in PDOX models. rHopQ may be useful for CEACAM-positive tumor and metastasis detection for pre-surgical diagnosis, intra-operative imaging and fluorescence-guided surgery.

Ordered subset expectation maximisation vs Bayesian penalised likelihood reconstruction algorithm in 18F-PSMA-1007 PET/CT

BackgroundThe aim of the study was to compare widely used ordered subset expectation maximisation (OSEM) algorithm with a new Bayesian penalised likelihood (BPL) Q.Clear algorithm in 18F-PSMA-1007 PET/CT.MethodsWe retrospectively assessed 25 18F-PSMA-1007 PET/CT scans with both OSEM and Q.Clear reconstructions available. Each scan was independently reported by two physicians both in OSEM and Q.Clear. SUVmax, SUVmean and tumour-to-background ratio (TBR) of each lesion were measured. Reports were also compared for their final conclusions and the number and localisation of lesions.ResultsIn both reconstructions the same 87 lesions were reported. Mean SUVmax, SUVmean and TBR were higher for Q.Clear than OSEM (7.01 vs 6.53 [p = 0.052], 4.16 vs 3.84 [p = 0.036] and 20.2 vs 16.8 [p < 0.00001], respectively). Small lesions (< 10 mm) had statistically significant higher SUVmax, SUVmean and TBR in Q.Clear than OSEM (5.37 vs 4.79 [p = 0.032], 3.08 vs 2.70 [p = 0.04] and 15.5 vs 12.5 [p = 0.00214], respectively). For lesions ≥ 10 mm, no significant differences were observed. Findings with higher tracer avidity (SUVmax ≥ 5) tended to have higher SUVmax, SUVmean and TBR values in Q.Clear (11.6 vs 10.3 [p = 0.00278], 7.0 vs 6.7 [p = 0.077] and 33.9 vs 26.7 [p < 0.00001, respectively). Mean background uptake did not differ significantly between Q.Clear and OSEM (0.42 vs 0.39, p = 0.07).ConclusionsIn 18F-PSMA-1007 PET/CT, Q.Clear SUVs and TBR tend to be higher (regardless of lesion localisation), especially for small and highly avid lesions. Increase in SUVs is also higher for lesions with high tracer uptake. Still, Q.Clear does not affect 18F-PSMA-1007 PET/CT specificity and sensitivity.

Relationship between primary tumour 18F-FDG uptake and immunohistochemical and clinical prognostic parameters in breast carcinoma

The objective of this study was to investigate the relationship between level of 18F-fluorodeoxyglucose (18F-FDG) accumulation in primary breast tumour assessed by positron emission tomography/computed tomography (PET/CT) and histopathological and clinical prognostic factors. A retrospective analysis was performed using the medical records of 58 female patients (age range: 31-86 years, mean age: 56) with biopsy of proven breast carcinoma, and who had undergone 18F-FDG PET/CT examination before chemotherapy/surgery. The 18F-FDG uptake of breast tumours was calculated as tumour to background ratio (TBR), which was compared with histopathological and clinical prognostic parameters. The histology of the breast tumour in the 58 patients was ductal type in 52 (90%), lobular in 4 (7%), and mucinous in 2 (3%). Tumour size was ≤ 2 cm in 31 (53%) patients, and > 2 cm in 27 (47%). The levels of TBRs were not significantly different between the patients groups with tumours of 2 cm or less and greater than 2 cm (P = 0.131). No significant difference between levels of TBR was observed neither with regards to axillary lymph node involvement (P = 0.065) nor in terms of distant metastases (p = 0.123). No statistically significant difference was found in levels of TBRs between patients with c-erbB-2 receptor positive and negative ones (P = 0.107). Progesterone receptor (PR) expression was observed in 33 patients (57%), and 25 patients (43%) were PR negative. As regards progesterone receptor status, a statistically significant difference was observed in mean TBR levels between patients with and without progesterone receptor expression (P = 0.020). Oestrogen receptor expression was positive in 41 (71%) patients, and negative in 17 (29%) patients. The difference in the levels of TBRs between patients with and without oestrogen receptor expression was at the level of significancy (P = 0.050). It is concluded that 18F-FDG uptake correlates with progesterone negativity of the tumour. However, a significant association with clinical prognostic parameters and level of 18F-FDG uptake levels could not be demonstrated. El objetivo de este estudio fue investigar la asociación entre el nivel de captación de 18F-fluorodeoxiglucosa (18F-FDG) en el tumor de mama primario, valorado mediante tomografía por emisión de positrones/tomografía computarizada (PET/TC) y correlacionarlo con los factores pronósticos histopatológicos y clínicos. Se analizaron retrospectivamente las historias clínicas de 58 mujeres (rango de edad: 31-86 años, edad media: 56 años) con biopsia de carcinoma de mama, que se sometieron a una exploración 18F-FDG PET/TC antes de la quimioterapia/cirugía. El grado de captación de 18F-FDG en los tumores de mama se calculó como el índice tumor/fondo (ITF) que se comparó con parámetros pronósticos histopatológicos y clínicos. La histología del tumor de mama en las 58 pacientes fue de tipo ductal en 52 (90%), lobular en 4 (7%) y mucinoso en 2 (3%). En 31 pacientes (53%) el tamaño del tumor fue ≤ 2 cm y en 27 (47%) fue > 2 cm. Los niveles de ITF no fueron significativamente diferentes entre el grupo de pacientes con un tumor ≤ 2 cm y el grupo con tumor > 2 cm (p = 0,131). No se observaron diferencias significativas entre los ITF ni con respecto a la afectación de los ganglios linfáticos axilares (p = 0,065), ni en términos de metástasis a distancia (p = 0,123). Tampoco hubo diferencias estadísticamente significativas en los niveles de ITF entre los pacientes con los receptores de c-erbB-2 positivos y negativos (p = 0,107). Treinta y tres pacientes (57%) presentaron receptores de progesterona positivos y en 25 pacientes (43%) eran negativos. Respecto al estado de los receptores de progesterona, se observó una diferencia estadísticamente significativa en los niveles medios de ITF entre pacientes con y sin la expresión del receptor de progesterona (p = 0,020). Los receptores estrogénicos fueron positivos en 41 pacientes (71%) y negativos en 17 (29%). Con relación a los receptores estrogénicos, la diferencia en el ITF entre los casos con receptores positivos y los negativos estaba en el nivel de significación (p = 0,050). Se concluye que la captación de 18F-FDG se relaciona con la negatividad de los receptores de progesterona del tumor. Sin embargo, no se demostró una asociación significativa con los parámetros pronósticos clínicos y el grado de captación de 18F-FDG.

Relationship between primary tumour 18F-FDG uptake and immunohistochemical and clinical prognostic parameters in breast carcinoma.

The objective of this study was to investigate the relationship between level of 18F-fluorodeoxyglucose (18F-FDG) accumulation in primary breast tumour assessed by positron emission tomography/computed tomography (PET/CT) and histopathological and clinical prognostic factors. A retrospective analysis was performed using the medical records of 58 female patients (age range: 31-86 years, mean age: 56) with biopsy of proven breast carcinoma, and who had undergone 18F-FDG PET/CT examination before chemotherapy/surgery. The 18F-FDG uptake of breast tumours was calculated as tumour to background ratio (TBR), which was compared with histopathological and clinical prognostic parameters. The histology of the breast tumour in the 58 patients was ductal type in 52 (90%), lobular in 4 (7%), and mucinous in 2 (3%). Tumour size was ≤ 2cm in 31 (53%) patients, and>2cm in 27 (47%). The levels of TBRs were not significantly different between the patients groups with tumours of 2cm or less and greater than 2cm (P=0.131). No significant difference between levels of TBR was observed neither with regards to axillary lymph node involvement (P=0.065) nor in terms of distant metastases (p=0.123). No statistically significant difference was found in levels of TBRs between patients with c-erbB-2 receptor positive and negative ones (P=0.107). Progesterone receptor (PR) expression was observed in 33 patients (57%), and 25 patients (43%) were PR negative. As regards progesterone receptor status, a statistically significant difference was observed in mean TBR levels between patients with and without progesterone receptor expression (P=0.020). Oestrogen receptor expression was positive in 41 (71%) patients, and negative in 17 (29%) patients. The difference in the levels of TBRs between patients with and without oestrogen receptor expression was at the level of significancy (P=0.050). It is concluded that 18F-FDG uptake correlates with progesterone negativity of the tumour. However, a significant association with clinical prognostic parameters and level of 18F-FDG uptake levels could not be demonstrated.

Predictive Value of 99mTc-MAA SPECT for 90Y-Labeled Resin Microsphere Distribution in Radioembolization of Primary and Secondary Hepatic Tumors.

This study analyzed the predictive value of (99m)Tc-labeled macroaggregated albumin ((99m)Tc-MAA) SPECT for (90)Y-labeled resin microsphere therapy (radioembolization) by comparing uptake on pretherapeutic (99m)Tc-MAA SPECT with uptake on posttherapeutic (90)Y-bremsstrahlung SPECT. We included 502 patients (55% male; mean age ± SD, 62 ± 11 y) who underwent radioembolization between 2005 and 2013 because of primary or secondary liver malignancies (colorectal cancer [n = 195, 38.8%], neuroendocrine tumors [n = 77, 15.3%], breast cancer [n = 68, 13.5%], hepatocellular carcinoma [n = 59, 11.8%], cholangiocellular carcinoma [n = 40, 8.0%], or urologic tumors [n = 14, 2.8%]). Manually drawn regions of interest around tumors and adjacent healthy liver tissue for up to 3 lesions per patient on (99m)Tc-MAA and (90)Y-bremsstrahlung scans were used to quantify mean counts per pixel and evaluate the mean tumor-to-background ratio (TBR). Data were given as mean ± SD. Additionally, uptake in lesions on (99m)Tc-MAA and (90)Y-bremsstrahlung scans was graded visually as homogeneously higher than (grade 1), heterogeneously higher than (grade 2), equal to (grade 3), or lower than (grade 4) uptake in normal liver tissue. The Mann-Whitney U test and Spearman correlation were used to evaluate statistically significant differences between (99m)Tc-MAA and (90)Y-bremsstrahlung SPECT. In total, 1,008 lesions were analyzed. Of the 23% (230/1,008) of lesions that had grade 1 uptake on (99m)Tc-MAA SPECT, 81% (186/230) remained grade 1 after radioembolization whereas 16% (37/230) were grade 2. Of the lesions with grade 2 uptake on (99m)Tc-MAA SPECT, 16% had grade 1 uptake and 82% grade 2 uptake after radioembolization. Of the lesions with grade 3 uptake, however, 27% had grade 1 uptake and 47% grade 2 uptake after radioembolization. Even among the lesions with grade 4 uptake on (99m)Tc-MAA SPECT, 21% had grade 1 uptake and 46% grade 2 uptake after radioembolization. The mean TBR on (99m)Tc-MAA and (90)Y-bremsstrahlung SPECT showed a significant, though low, correlation in the total population (r = 0.26; P < 0.001) and in hepatocellular carcinoma (r = 0.4; P < 0.001), cholangiocellular carcinoma (r = 0.3; P < 0.05), breast cancer (r = 0.3; P < 0.001), colorectal cancer (r = 0.2; P < 0.001), and neuroendocrine tumors (r = 0.2; P < 0.01). Although significant for most lesions, the correlation between (99m)Tc-MAA and (90)Y-microsphere mean TBR was low. Classifying uptake into 4 grades revealed that lesions with high uptake on (99m)Tc-MAA SPECT maintain high uptake within radioembolization. More than 60% of lesions with a pretherapeutically lower uptake than in healthy liver tissue, however, showed high uptake within radioembolization. Patients with low tumor uptake on pretherapeutic (99m)Tc-MAA imaging should not be excluded from radioembolization.

Intraoperative Molecular Imaging of Lung Adenocarcinoma Can Identify Residual Tumor Cells at the Surgical Margins.

During lung surgery, identification of surgical margins is challenging. We hypothesized that molecular imaging with a fluorescent probe to pulmonary adenocarcinomas could enhance residual tumor during resection. Mice with flank tumors received a contrast agent targeting folate receptor alpha. Optimal dose and time of injection was established. Margin detection was compared using traditional methods versus molecular imaging. A pilot study was then performed in three humans with lung adenocarcinoma. The peak tumor-to-background ratio (TBR) of murine tumors was 3.9. Fluorescence peaked at 2 h and was not improved beyond 0.1 mg/kg. Traditional inspection identified 30% of mice with positive margins. Molecular imaging identified an additional 50% of residual tumor deposits (p < 0.05). The fluorescent probe visually enhanced all human tumors with a mean TBR of 3.5. Molecular imaging is an important adjunct to traditional inspection to identify surgical margins after tumor resection.

18F]FLT is superior to [18F]FDG for predicting early response to antiproliferative treatment in high-grade lymphoma in a dose-dependent manner

Positron emission tomography (PET) with the thymidine analogue [(18)F]fluorothymidine ([(18)F]FLT) has been shown to detect early response to chemotherapy in high-grade lymphoma. In this preclinical in vitro and in vivo study we compared [(18)F]FLT to the glucose analogue [(18)F]fluorodeoxyglucose ([(18)F]FDG) regarding dose-dependent visualization and prediction of early therapy response. Immunodeficient mice bearing human diffuse large B-cell lymphoma (SUDHL-4) xenotransplants were treated intraperitoneally with increasing doses of the cytotoxic agent doxorubicin. Metabolic and antiproliferative effects were assessed 2days after therapy by [(18)F]FLT and [(18)F]FDG PET. Explanted lymphomas were analysed histologically and by immunostaining against Ki67 and caspase 3. In vitro, lymphoma cells were incubated with increasing concentrations of doxorubicin and analysed using the tetrazolium assay, fluorescence-activated cell sorting, and [(18)F]FLT and [(18)F]FDG uptake 48h later. In vivo, tumour growth was inhibited by doses of doxorubicin ranging from 25μg to 200μg. The mean tumour-to-background ratio (TBR) of [(18)F]FLT on day +2 was significantly reduced in all dose groups compared to control and baseline values and preceded changes in tumour volume. Importantly, there was a significant inverse correlation between reduction in TBR and dose of chemotherapy (r = -0.54, p = 0.021). The mean TBR of [(18)F]FDG, however, increased after therapy and differed considerably between groups (r = -0.13, p = 0.668). Explanted tumours showed a dose-dependent decrease in the proliferation marker Ki67, but no change in the apoptotic marker caspase 3. In vitro, doxorubicin led to a dose-dependent reduction in cell viability and a decrease in S phase. Lymphoma cells showed a dose-dependent reduction in [(18)F]FLT uptake, in contrast to a variable and decelerated reduction in [(18)F]FDG uptake. Thus, the increase in [(18)F]FDG uptake in vivo presumably reflected nonspecific glucose metabolism of inflammatory cells, as confirmed by histology of explanted lymphomas. Early responses to dose-dependent antiproliferative treatment in high-grade lymphoma are more accurately visualized with [(18)F]FLT PET than with [(18)F]FDG PET.

Performance of 18F-Fluoro-Ethyl-Tyrosine (18F-FET) PET for the Differential Diagnosis of Primary Brain Tumor: A Systematic Review and Metaanalysis

For the past decade, PET with (18)F-fluoro-ethyl-tyrosine ((18)F-FET) has been used in the evaluation of patients with primary brain tumors (PBTs), but so far series have reported only a limited number of patients. The purpose of this systematic review and metaanalysis was to assess the diagnostic performance of (18)F-FET PET in patients with suspicion of PBT. We examined studies published in the literature using MEDLINE and EMBASE databases. Inclusion criteria were use of (18)F-FET PET for initial assessment of patients with a newly diagnosed brain lesion; patients who had no radiotherapy, surgery, or chemotherapy before (18)F-FET PET; and use of histology as a gold standard. Metaanalysis was performed on a per-patient basis. We secondarily performed receiver-operating-characteristic analysis of pooled patients to determine tumor-to-background ratio (TBR) of (18)F-FET uptake and best diagnostic value. Thirteen studies totaling 462 patients were included. For the diagnosis of PBT, (18)F-FET PET demonstrated a pooled sensitivity of 0.82 (95% confidence interval [CI], 0.74-0.88), specificity of 0.76 (95% CI, 0.44-0.92), area under the curve of 0.84 (95% CI, 0.80-0.87), positive likelihood ratio of 3.4 (95% CI, 1.2-9.5), and negative likelihood ratio of 0.24 (95% CI, 0.14-0.39). Receiver-operating-characteristic analysis indicated that a mean TBR threshold of at least 1.6 and a maximum TBR of at least 2.1 had the best diagnostic value for differentiating PBTs from nontumoral lesions. (18)F-FET PET demonstrated excellent performance for diagnosing PBTs. Strict standardization of PET acquisition protocols and prospective, multicenter studies investigating the added value over current MRI are now needed to establish (18)F-FET PET as a highly relevant tool for patient management.

Thallium-201 Scintigraphy Is an Effective Diagnostic Modality to Distinguish Malignant From Benign Soft-Tissue Tumors

The aim of this study is to evaluate whether thallium-201 (201-Tl) scintigraphy can differentiate malignant from benign soft-tissue tumors. Between April 1995 and December 2005, 192 patients with soft-tissue tumors (85 malignant and 107 benign) underwent 201-Tl scintigraphy before treatment. Isotope uptake was used as a proxy for tumor-to-background ratio (TBR). The accuracy of TBR on early and delayed imaging was evaluated using the Mann-Whitney U and χ(2) tests. There was a statistically significant difference in mean TBR on early and delayed imaging of malignant and benign soft-tissue tumors (124% ± 109% vs. 22% ± 42%, and 82% ± 83% vs. 12% ± 25%, P < 0.0001). A TBR cutoff of 20% indicated the probability of malignancy on early and delayed imaging (82% sensitivity and 77% specificity; 82% sensitivity and 84% specificity, P < 0.0001). Well-differentiated liposarcomas showed low isotope accumulation, while pigmented villonodular synovitis and giant cell tumors of the tendon sheath showed high isotope accumulation. Thallium-201 scintigraphy can distinguish malignant from benign tumors with relatively high accuracy. With the exception of low grade liposarcomas and locally aggressive benign tumors, 201-Tl scintigraphy may be an effective diagnostic modality to differentiate malignant from benign soft-tissue tumors.

Detection of Oral Squamous Cell Carcinoma and Cervical Lymph Node Metastasis Using Activatable Near-Infrared Fluorescence Agents

To assess the feasibility of optical imaging using activatable near-infrared fluorescence (NIRF) agents to detect oral cancer and cervical lymph node metastasis in vivo. In vivo study. University medical center. Female nude mice aged 4 to 6 weeks. Luciferase-expressing OSC-19-luc cells were injected into the tongues of nude mice. A control group of nude mice was injected in the tongue with a physiologic saline solution. Tumor growth was followed by bioluminescence imaging. After 3 weeks, animals were randomly allocated to intravenous administration of 1 of 2 activatable NIRF agents: ProSense680 or MMPSense680. Fluorescence imaging of the mice was performed, and the tumor to background ratio (TBR) was determined on histologic sections of the tongue and cervical lymph nodes after resection at necropsy. Fluorescence signals. The fluorescence signals in tongue tumor and cervical lymph node metastases were significantly higher than those in control animals. The mean (SD) TBR of ProSense680 in the tongue was 15.8 (8.1) and in the lymph nodes was 11.8 (3.6). For MMPSense680, the mean (SD) TBR in the tongue was 18.6 (9.4) and in the lymph nodes was 10.5 (4.0). Oral cancer and cervical lymph node metastases can be detected by targeting increased proteolytic activity at the tumor borders using NIRF optical imaging. These NIRF agents could be used for real-time image-guided surgery, which has the potential to improve the complete surgical resection of oral cancer.