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One of the hallmarks of cancer is increased cell proliferation. Measurements of cell proliferation by estimation of DNA synthesis with several radiolabeled nucleosides have been tested to assess tumor growth. Deoxycytidine can be phosphorylated by deoxycytidine kinase (dCK) and is incorporated into DNA. This study evaluated a radiofluorinated deoxycytidine analog, 5-[ 18 F]fluoro-2'-deoxycytidine ([ 18 F]FdCyd), as a proliferation probe and compared it with 5-[ 18 F]fluoro-2'-deoxyuridine ([ 18 F]FdUrd), 3'-deoxy-3'-[ 18 F]fluorothymidine ([ 18 F]FLT), and [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) in a tumor-bearing mouse model. [ 18 F]FdCyd was synthesized from two precursors by direct electrophilic substitution. The serum stability and partition coefficient of [ 18 F]FdCyd were evaluated in vitro. Positron emission topography (PET) imaging of Lewis lung carcinoma (LLC)-bearing mice with [ 18 F]FdCyd, [ 18 F]FdUrd, [ 18 F]FLT, and [ 18 F]FDG were evaluated. [ 18 F]FdCyd was stable in mouse serum and normal saline for up to 4 h. With all radiotracers except [ 18 F]FLT, PET can clearly delineate the tumor lesion. [ 18 F]FdCyd and [ 18 F]FdUrd showed high accumulation in the liver and kidney. The SUV and tumor-to-muscle (T/M) ratios derived from PET imaging of the radiotracers were [ 18 F]FDG > [ 18 F]FdCyd > [ 18 F]FdUrd > [ 18 F]FLT. Selective retention in tumors with a favorable tumor/muscle ratio makes [ 18 F]FdCyd a protential candidate for further investigation as a proliferation imaging agent., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Radiolabeled Arg-Gly-Asp (RGD) peptide analogs have been extensively studied for αvβ3 integrin-targeted angiogenesis imaging. According to recently presented evidence, the dodecapeptide GE11 has high affinity to the epidermal growth factor receptor (EGFR), which is overexpressed in many types of cancer. Dual-receptor molecular imaging probes with two different heterodimeric peptides exhibit improved cancer targeting efficacy. In the present study, the design and synthesis of a new RGD-GE11 peptide heterodimer for dual αvβ3 integrin/EGFR-targeted cancer imaging are described. The RGD-GE11 heterodimer was linked with 6-aminohexanoic acid (6-Ahx) and cysteine and conjugated with 1,4,7-triazacyclononane-N,N',N″-triacetic acid (NOTA) to form NOTA-RGD-cys-6-Ahx-GE11. The monomeric peptides, NOTA-cys-6-Ahx-GE11 and c(RGDyK), were formed by a peptide synthesizer. The peptide heterodimer NOTA-RGD-GE11 was obtained by NOTA-cys-6-Ahx-GE11 and maleimidopropyl-c(RGDyK) conjugation with a thioether linkage. The NOTA peptide conjugate was labeled with freshly eluted (68)Ga and purified using reversed-phase high-performance liquid chromatography. The (68)Ga-NOTA-RGD-cys-6-Ahx-GE11 was successfully prepared, in this study, with a radiochemical yield of 85% and a radiochemical purity of >98%. These results warrant further investigation of this heterodimeric peptide's binding affinity to the receptors., (Copyright © 2015 John Wiley & Sons, Ltd.)

Introduction: Benzamide can specifically bind to melanoma cells. A 18F-labeled benzamide derivative, [18F]N-(2-diethylaminoethyl)-4-[2-(2-(2-fluoroethoxy) ethoxy)ethoxy]benzamide ([18F]FPBZA), was developed as a promising PET probe for primary and metastatic melanoma., Methods: [18F]FPBZA was synthesized via a one-step radiofluorination in this study. The specific uptake of [18F]FPBZA was studied in B16F0 melanoma cells, A375 amelanotic melanoma cells, and NB-DNJ-pretreated B16F0 melanoma cells. The biological characterization of [18F]FPBZA was performed on mice bearing B16F0 melanoma, A375 amelanotic melanoma, or inflammation lesion., Results: [18F]FPBZA can be prepared efficiently with a yield of 40-50%. The uptake of [18F]FPBZA by B16F0 melanoma cells was significantly higher than those by A375 tumor cells and NB-DNJ-pretreated B16F0 melanoma cells. B16F0 melanoma displayed prominent uptake of [18F]FPBZA at 2 h (7.81±0.82%ID/g), compared with A375 tumor and inflammation lesion (3.00±0.71 and 1.67±0.56%ID/g, resp.). [18F]FPBZA microPET scan clearly delineated B16F0 melanoma but not A375 tumor and inflammation lesion. In mice bearing pulmonary metastases, the lung radioactivity reached 4.77±0.36%ID/g at 2 h (versus 1.16±0.23%ID/g in normal mice)., Conclusions: Our results suggested that [18F]FPBZA PET would provide a promising and specific approach for the detection of primary and metastatic melanoma lesions.

Quantification of the expression of asialoglycoprotein receptor (ASGPR), which is located on the hepatocyte membrane with high-affinity for galactose residues, can help assess ASGPR-related liver diseases. A hepatic fibrosis mouse model with lower asialoglycoprotein receptor expression was established by dimethylnitrosamine (DMN) administration. This study developed and demonstrated that 4-(18)F-fluoro-N-(6-((3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)hexyl)benzamide ((18)F-FBHGal), a new (18)F-labeled monovalent galactose derivative, is an asialoglycoprotein receptor (ASGPR)-specific PET probe in a normal and a hepatic fibrosis mouse models. Immunoassay exhibited a linear correlation between the accumulation of GalH-FITC, a fluorescent surrogate of FBHGal, and the amount of ASGPR. A significant reduction in HepG2 cellular uptake (P <0.0001) was observed using confocal microscopy when co-incubated with 0.5μM of asialofetuin, a well known ASGPR blocking agent. Animal studies showed the accumulation of (18)F-FBHGal in fibrosis liver (14.84±1.10 %ID/g) was appreciably decreased compared with that in normal liver (20.50±1.51 %ID/g, P <0.01) at 30min post-injection. The receptor indexes (liver/liver-plus-heart ratio at 30min post-injection) of hepatic fibrosis mice derived from both microPET imaging and biodistribution study were significantly lower (P <0.01) than those of normal mice. The pharmacokinetic parameters (T(1/2)α, T(1/2)β, AUC and Cl) derived from microPET images revealed prolonged systemic circulation of (18)F-FBHGal in hepatic fibrosis mice compared to that in normal mice. The findings in biological characterizations suggest that (18)F-FBHGal is a feasible agent for PET imaging of hepatic fibrosis in mice and may provide new insights into ASGPR-related liver dysfunction., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

[(18)F]Flurobutyl ethacrynic amide ([(18)F]FBuEA) was prepared from the precursor tosylate N-Boc-N-[4-(toluenesulfonyloxy)butyl]ethacrynic amide with a radiochemical yield of 3%, a specific activity of 48 GBq/μmol and radiochemical purity of 98%. Chemical conjugation of [(18)F]FBuEA with glutathione (GSH) via a self-coupling reaction and enzymatic conjugation under catalysis of glutathiontransferase alpha (GST-α) and π provided about 41% yields of radiochemical conjugated product [(18)F]FBuEA-GSH, 85% and 5-16%, respectively. The catalytic selectivity of this tracer toward GST-alpha was addressed. Positron emission tomography (PET) imaging of [(18)F]FBuEA in normal rats showed that a homogeneous pattern of radioactivity was distributed in the liver, suggesting a catalytic role of GST. By contrast, PET images of [(18)F]FBuEA in rats with thioacetamide-induced cholangiocarcinoma displayed a heterogeneous pattern of radioactive accumulation with cold spots in tumor lesions. PET imaging with [(18)F]FBuEA could be used for early diagnosis of hepatic tumor with a low GST activity as well as liver function., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

(18)F-labeled sodium fluoride ([(18)F]NaF) is a useful bone imaging agent that has been demonstrated to be significantly more accurate than (99m)Tc-labeled methylene diphosphonate for the detection of both sclerotic and lytic lesions in various malignancies. A reliable anion-exchange HPLC method equipped with suppressed conductivity and radioactive detectors has been developed in order to analyze the content of NaF and radiochemical purity in [(18)F]NaF radiopharmaceuticals. The method described for fluoride analysis uses an isocratic elution of NaF in a Hamilton anion-exchange column using a mobile phase that consists of 7.5 mM sodium carbonate and 0.018 mM potassium thiocyanate. The flow rate was 1.0 ml/min. The method was validated in accordance with several parameters, including system suitability, specificity, precision, accuracy, linearity, robustness, limit of detection and limit of quantification. The results are described as follows: (1) The system suitability includes the tailing factor, theoretical plate number and resolution, which are 1.192534, 2729.6594 and 16.7415, respectively. (2) For specificity, the solvent peak and chloride ion did not interfere with the retention time of the fluoride. (3) The percentage coefficient of variation for analysis of precision, including repeatability and intermediate precision, is less than 2.0%. (4) Accuracy of method is within the range of 98%-102%. (5) The range of linearity is from 10 to 400 μg/ml, with the correlation coefficient (R(2)) always being above 0.9985. (6) The data of method robustness are within acceptance criteria. (7) The limit of detection and limit of quantification are 0.0678 and 0.20 μg/ml, respectively. All of the analysis results demonstrate that this method is highly sensitive, convenient, specific and suitable for quantification of NaF over a wide linear range. Therefore, the method can be successfully performed for routine analysis of fluoride content in [(18)F]NaF radiopharmaceuticals and reduce the time required for analysis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background/objectives: Intratumoral injection of a radiopharmaceutical is a potential modality to treat liver tumors. Rhenium-188 ((188)Re) was used to chelate with ethyl cysteinate dimer (ECD) in lipiodol solution to form (188)Re-ECD/lipiodol, which was then evaluated for its therapeutic potential in a rodent hepatoma model., Materials and Methods: Male Sprague-Dawley rats were implanted with N1-S1 hepatoma cells orthotopically and randomly divided into two groups. Group 1 (n = 29) and group 2 (n = 10) received (188)Re-ECD/lipiodol (30.4 +/- 21.8 MBq/0.1 mL) and 0.1 mL of normal saline by intratumoral injection, respectively. Three rats in group 1 were imaged by micro-single-photon emission computed tomography/computed tomography scan to evaluate the biodistribution pattern. All rats were monitored for change of tumor size and survival rate after 2 months., Results: The in vitro stability test showed that (188)Re-ECD was well-retained in the lipiodol phase for 48 hours. The biodistribution image revealed that radioactivity was retained well in hepatomas 24 hours postinjection. Long-term studies demonstrated that rats treated with (188)Re-ECD/Lipiodol had smaller tumor volumes and a better survival rate, compared to the control group. At the end of observation, the survival rates in groups 1 and 2 were 62% and 20%, respectively (p < 0.05)., Conclusions: (188)Re-ECD/lipiodol via direct intratumoral injection shows potential for treating hepatoma and warrants further clinical trials.

Gastrin-releasing peptide receptors (GRPRs) are overexpressed on a variety of human tumors, such as prostate, breast, and lung cancer. Bombesin (BN) is a 14-amino-acid peptide with high affinity for these GRPRs. We synthesized DTPA-Q-K-Y-G-N-Q-W-A-V-G-H-L-M, a 13-amino-acid peptide chelated with diethylenetriaminepentaacetic acid (DTPA), and radiolabeled this BN analog with 111InCl(3). Biologic activity of 111In-[DTPA(1), Lys(3), Tyr(4)]-BN was evaluated in PC-3 prostate tumor-bearing severely compromised immunodeficient (SCID) mice. The purity of synthesized [DTPA(1), Lys(3), Tyr(4)]-BN was greater than 95%. The radiolabeling efficiency of 111In-[DTPA(1), Lys(3), Tyr(4)]-BN was 96.9% +/- 2.46%. The IC(50) and K(i) of [DTPA(1), Lys(3), Tyr(4)]-BN in the human bombesin 2 receptor were 1.05 +/- 0.46 and 0.83 +/- 0.36 nM, respectively. The K(d) of 111In-[DTPA(1), Lys(3), Tyr(4)]-BN in GRPR-expressing PC-3 tumor cells was 22.9 +/- 6.81 nM. Both biodistribution and micro-SPECT/CT (single-photon emission computed tomography/computed tomography) imaging studies with 111In-[DTPA(1), Lys(3), Tyr(4)]-BN demonstrated the highest uptake at 8 hours postinjection. The Pearson correlation analysis showed a positive correlation of tumor uptake between biodistribution and micro-SPECT/CT semiquantification imaging analysis (r = 0.832). Our results revealed 111In-[DTPA(1), Lys(3), Tyr(4)]-BN has high affinity with BN type 2 receptor. The results demonstrated a good uptake in the GRPR-overexpression of PC-3 tumor-bearing SCID mice. 111In-[DTPA(1), Lys(3), Tyr(4)]-BN is a potential agent for imaging GRPR-positive tumors in humans.

A suitable three potential-time waveforms for the electrochemical detection of 2-deoxy-2-chloro-d-glucose (ClDG) by gold working electrode and palladium reference electrode have been developed and method validation was performed on Waters 2796 Bioalliance HPLC system coupled with pulsed amperometric detection (HPLC/PAD). FDG and ClDG could be completely separated by 50 mM NaOH mobile phase at a flow rate of 1.0 ml/min; 30 degrees C analytical column temperature; and E1 of 200 mV, T1 of 900 mS; E2 of -770 mV, T2 of 10 mS; E3 of 1400 mV, T3 of 10 mS; acquisition delay (AD) of 300 mS. The validation results were shown as follows: (1) in specificity study, mannose, FDG and ClDG could be completely separated and the retention times of these were 6.2, 11.1 and 13.5 min, respectively, with a total run time of 20 min; (2) the intraday repeatable precision expressed with the CV% in six successive analysis was 0.52% (for FDG) and 0.83% (for ClDG); (3) the interday variability precision expressed with the CV% value of the repeatable precision of 3 days was 0.99%, 0.52% and 0.58% for FDG and 0.71%, 0.83% and 1.24% for ClDG; both the CV% of intraday and interday reproducibilities of FDG and ClDG were better than 1.5%; (4) the accuracy and recovery of FDG and ClDG expressed with the percentage of mean value of three successive analysis were 99.75% (for FDG) and 100.68% (for ClDG) which were all greater than 95%; (5) under optimum conditions, the limit of detection of FDG and ClDG was 0.41 and 0.68 microg/ml, and the limit of quantization of FDG and ClDG was 1.24 and 2.04 microg/ml; (6) the correlation coefficient (r) value of linearity is over 0.999 by 5-50 microg/ml ranges of both compounds, respectively; (7) no interference peak effects by composition of mobile phase or increasing/decreasing flow rate or change of temperature was observed.

Purpose: This article evaluates [18F] fluorodeoxyglucose positron emission tomography (18F-FDG-PET) findings as a predictor for local responders (R) vs. nonresponders (NR) in nasopharyngeal carcinoma (NPC) patients with Stage T4 lesions, before and at 3 months after completion of concurrent chemotherapy and radiation therapy (CCRT)., Methods and Materials: From January 2002 to November 2003, 39 T4 NPC patients were enrolled. All had magnetic resonance imaging and 18F-FDG-PET, both before and 3 months after CCRT. Any residual/recurrent lesions were confirmed histopathologically., Results: Of the 39 eligible patients, after a follow-up of 24.2 +/- 9.5 months, 35 became disease-free and 4 had residual or recurrent disease. Marginal differences in standard uptake values (SUV) were observed (10.9 +/- 5.3 vs. 15.6 +/- 3.4, p = 0.058) between R and NR before treatment, and value changes of SUV before and after CCRT were not significantly different. However, highly significantly lower values of SUV were noted for R than for NR 3 months after completion of CCRT (2.1 +/- 0.8 vs. 5.5 +/- 3.2, p = 0.001). One hundred percent positive and negative predictive values were observed for SUV values of 4.0, set 3 months after completion of CCRT., Conclusions: Neither the pretreatment SUV nor the changes of SUV between pretreatment and posttreatment were significant predictors for local response. SUV at 3 months after completion of CCRT was a significant determinator for local response. The cutoff of 4.0 for SUV at 3 months after completion of CCRT was useful to be offered as a diagnostic reference for recurrent or residual tumor for NPC treatment.

Purpose: The role of positron emission tomography (PET) with fluorine-18-labeled fluoro-2-deoxy-d-glucose (FDG) in cervical cancer has not yet been well defined. We conducted a prospective study to investigate its efficacy in comparison with magnetic resonance imaging and/or computed tomography (MRI-CT)., Materials and Methods: Patients with untreated locally advanced (35%) or recurrent (65%) cervical cancer were enrolled onto this study. In the first part of this study, 41 patients had a conventional FDG-PET (40 minutes after injection), and in the second part, 94 patients received dual-phase PET (at both 40 minutes and 3 hours after injection). The overall results of PET scans were compared with MRI-CT, and the two protocols of PET were also compared with each other. Lesion status was determined by pathology results or clinical follow-up. The receiver operating characteristic curve method with area under the curve (AUC) calculation was used to evaluate the discriminative power., Results: Overall (N = 135), FDG-PET was significantly superior to MRI-CT in identifying metastatic lesions (AUC, 0.971 v 0.879; P =.039), although the diagnostic accuracy was similar for local tumors. Dual-phase PET was also significantly better than the 40-minute PET (n = 94). The latter accurately recognized 70% of metastatic lesions and the former detected 90% (AUC, 0.943 v 0.951; P =.007). Dual-phase FDG-PET changed treatment of 29 patients (31%; upstaging 27% and downstaging 4%)., Conclusion: This study shows that dual-phase FDG-PET is superior to conventional FDG-PET or MRI-CT in the evaluation of metastatic lesions in locally advanced or recurrent cervical cancer.

Abstract: Introduction: 99mTc-labeled macroaggregated albumin (99mTc-MAA) scintigraphy scan is routinely performed for lung perfusion imaging and for the assessment of in vivo distribution of 90Y-labeled SIR-Spheres prior to selective internal radiation treatment for hepatocellular carcinoma. Positron emission tomography (PET) imaging is superior to gamma scintigraphy in terms of sensitivity, spatial resolution and accuracy of quantification. This study reported that 18 F-labeled macroaggregated albumin (18 F-MAA) is an ideal PET imaging surrogate for 99mTc-MAA. Methods: 18 F-MAA was prepared from the commercial MAA kit via a one-step conjugation with N-succinimidyl 4-18 F-fluorobenzoate (18 F-SFB). The biodistribution study and microPET/microSPECT imaging were conducted in normal SD rats after intravenous injection of 18 F-MAA/99mTc-MAA. A comparison study of these two radiotracers was performed after co-injection via the intrahepatic arterial in a N1S1 hepatoma-bearing SD rat model. Results: The optimal condition for 18 F-MAA preparation is coupling MAA (0.5mg) with 18 F-SFB at 45°C for 5min in a phosphate buffer of pH 8.5. 18 F-MAA was prepared in 60min with high radiochemical yield (30%–35%) and high radiochemical purity (>95%). The in vivo distribution of 18 F-MAA after intravenous injection meets the specifications of MAA depicted in European Pharmacopeia. Our study demonstrated excellent correlation between 18 F-MAA and 99mTc-MAA in the regional distribution of tumor, liver and lungs (R2 =0.965, 0.886 and 0.991, respectively), and also in the tumor-to-liver and tumor-to-lungs ratio (R2 =0.965 and 0.987, respectively) in a N1S1 hepatoma-bearing SD rat model. The organ uptakes derived from animal PET/CT and SPECT/CT imaging after administration of these two tracers were in accordance with those obtained in the distribution studies. Conclusions: Starting from commercial MAA kit, an efficient preparation of 18 F-MAA was successfully established. Highly correlated, almost parallel, regional distribution of 18 F-MAA and 99mTc-MAA in both normal rats and hepatoma-bearing rats was observed. The findings, taken together, demonstrate that 18 F-MAA is an ideal surrogate for 99mTc-MAA for clinical PET applications. [Copyright &y& Elsevier]

Abstract: Introduction: Hepatocellular carcinoma is the most common form of primary hepatic carcinoma. A new N2S2 tetradentate ligand, N-[2-(triphenylmethyl)thioethyl]-3-aza-19-ethyloxycarbonyl-3-[2-(triphenylmethyl)thioethyl]octadecanoate (H3MN-16ET), was introduced and labeled with 188Re to create 188Re-MN-16ET in the Lipiodol phase. The potential of 188Re-MN-16ET/Lipiodol for hepatoma therapy was evaluated in a hepatocellular carcinoma animal model of Sprague–Dawley rats implanted with the N1S1 cell line. Methods: Synthesis of H3MN-16ET was described, and characterization was identified by infrared, nuclear magnetic resonance and mass spectra. We compared the effects of transchelating agents (glucoheptonate or tartaric acid) and a reducing agent (stannous chloride) on the complexing of 188Re-perrhenate and H3MN-16ET. Twenty-four rats implanted with hepatoma were injected with 3.7 MBq/0.1 ml of 188Re-MN-16ET/Lipiodol or 188Re-MN-16ET via transcatheter arterial embolization. Biodistribution experiments and single-photon emission computed tomography imaging were performed to investigate tumor accumulation. Results: H3MN-16ET was proved to easily conjugate with the Re isotope and showed good solubility in Lipiodol. The radiochemical purity of 188Re-MN-16ET/Lipiodol with 10 mg tartaric acid and stannous chloride was shown to be more than 90%. The major distribution sites of 188Re-MN-16ET in Sprague–Dawley rats were hepatoma and the liver. However, the radioactivity at the tumor site postadministered with 188Re-MN-16ET was quickly decreased from 9.15±0.23 (at 1 h) to 2.71%±0.18% of injected dose/g (at 48 h). The biodistribution and micro-single-photon emission computed tomography/computed tomography image data showed that 188Re-MN-16ET/Lipiodol was selectively retained at the tumor site, with 11.55±1.44, 13.16±1.46 and 10.67%±0.95% of injected dose/g at 1, 24 and 48 h postinjection, respectively. The radioactivity in normal liver tissue was high but significantly lower than that of the tumors. Conclusion: H3MN-16ET is a suitable tetradentate ligand for 188Re labeling. From the animal data, we suggest that 188Re-MN-16ET/Lipiodol has the potential to be a therapeutic radiopharmaceutical for hepatoma treatment. [Copyright &y& Elsevier]

Abstract: 18F-labeled sodium fluoride ([18F]NaF) is a useful bone imaging agent that has been demonstrated to be significantly more accurate than 99mTc-labeled methylene diphosphonate for the detection of both sclerotic and lytic lesions in various malignancies. A reliable anion-exchange HPLC method equipped with suppressed conductivity and radioactive detectors has been developed in order to analyze the content of NaF and radiochemical purity in [18F]NaF radiopharmaceuticals. The method described for fluoride analysis uses an isocratic elution of NaF in a Hamilton anion-exchange column using a mobile phase that consists of 7.5 mM sodium carbonate and 0.018 mM potassium thiocyanate. The flow rate was 1.0 ml/min. The method was validated in accordance with several parameters, including system suitability, specificity, precision, accuracy, linearity, robustness, limit of detection and limit of quantification. The results are described as follows: (1) The system suitability includes the tailing factor, theoretical plate number and resolution, which are 1.192534, 2729.6594 and 16.7415, respectively. (2) For specificity, the solvent peak and chloride ion did not interfere with the retention time of the fluoride. (3) The percentage coefficient of variation for analysis of precision, including repeatability and intermediate precision, is less than 2.0%. (4) Accuracy of method is within the range of 98%–102%. (5) The range of linearity is from 10 to 400 μg/ml, with the correlation coefficient (R 2) always being above 0.9985. (6) The data of method robustness are within acceptance criteria. (7) The limit of detection and limit of quantification are 0.0678 and 0.20 μg/ml, respectively. All of the analysis results demonstrate that this method is highly sensitive, convenient, specific and suitable for quantification of NaF over a wide linear range. Therefore, the method can be successfully performed for routine analysis of fluoride content in [18F]NaF radiopharmaceuticals and reduce the time required for analysis. [Copyright &y& Elsevier]

Purpose: This article evaluates [18F] fluorodeoxyglucose positron emission tomography (18F-FDG-PET) findings as a predictor for local responders (R) vs. nonresponders (NR) in nasopharyngeal carcinoma (NPC) patients with Stage T4 lesions, before and at 3 months after completion of concurrent chemotherapy and radiation therapy (CCRT). Methods and Materials: From January 2002 to November 2003, 39 T4 NPC patients were enrolled. All had magnetic resonance imaging and 18F-FDG-PET, both before and 3 months after CCRT. Any residual/recurrent lesions were confirmed histopathologically. Results: Of the 39 eligible patients, after a follow-up of 24.2 +/- 9.5 months, 35 became disease-free and 4 had residual or recurrent disease. Marginal differences in standard uptake values (SUV) were observed (10.9 +/- 5.3 vs. 15.6 +/- 3.4, p = 0.058) between R and NR before treatment, and value changes of SUV before and after CCRT were not significantly different. However, highly significantly lower values of SUV were noted for R than for NR 3 months after completion of CCRT (2.1 +/- 0.8 vs. 5.5 +/- 3.2, p = 0.001). One hundred percent positive and negative predictive values were observed for SUV values of 4.0, set 3 months after completion of CCRT. Conclusions: Neither the pretreatment SUV nor the changes of SUV between pretreatment and posttreatment were significant predictors for local response. SUV at 3 months after completion of CCRT was a significant determinator for local response. The cutoff of 4.0 for SUV at 3 months after completion of CCRT was useful to be offered as a diagnostic reference for recurrent or residual tumor for NPC treatment. [ABSTRACT FROM AUTHOR]