Cervical lymph node metastasis prediction of postoperative papillary thyroid carcinoma before 131I therapy based on clinical and ultrasound characteristics.

Background: The status of lymph nodes is crucial to determine the dose of radioiodine-131(131I) for postoperative papillary thyroid carcinoma (PTC). We aimed to develop a nomogram for predicting residual and recurrent cervical lymph node metastasis (CLNM) in postoperative PTC before 131I therapy. Method: Data from 612 postoperative PTC patients who underwent 131I therapy from May 2019 to December 2020 were retrospectively analyzed. Clinical and ultrasound features were collected. Univariate and multivariate logistic regression analyses were performed to determine the risk factors of CLNM. Receiver operating characteristic (ROC) analysis was used to weigh the discrimination of prediction models. To generate nomograms, models with high area under the curves (AUC) were selected. Bootstrap internal validation, calibration curves and decision curves were used to assess the prediction model's discrimination, calibration, and clinical usefulness. Results: A total of 18.79% (115/612) of postoperative PTC patients had CLNM. Univariate logistic regression analysis found serum thyroglobulin (Tg), serum thyroglobulin antibodies (TgAb), overall ultrasound diagnosis and seven ultrasound features (aspect transverse ratio, cystic change, microcalcification, mass hyperecho, echogenicity, lymphatic hilum structure and vascularity) were significantly associated with CLNM. Multivariate analysis revealed higher Tg, higher TgAb, positive overall ultrasound and ultrasound features such as aspect transverse ratio ≥ 2, microcalcification, heterogeneous echogenicity, absence of lymphatic hilum structure and abundant vascularity were independent risk factors for CLNM. ROC analysis showed the use of Tg and TgAb combined with ultrasound (AUC = 0.903 for "Tg+TgAb+Overall ultrasound" model, AUC = 0.921 for "Tg+TgAb+Seven ultrasound features" model) was superior to any single variant. Nomograms constructed for the above two models were validated internally and the C-index were 0.899 and 0.914, respectively. Calibration curves showed satisfied discrimination and calibration of the two nomograms. DCA also proved that the two nomograms were clinically useful. Conclusion: Through the two accurate and easy-to-use nomograms, the possibility of CLNM can be objectively quantified before 131I therapy. Clinicians can use the nomograms to evaluate the status of lymph nodes in postoperative PTC patients and consider a higher dose of 131I for those with high scores.

Evaluation of a respiratory motion-corrected image reconstruction algorithm in 2-[18F]FDG and [68Ga]Ga-DOTA-NOC PET/CT: impacts on image quality and tumor quantification.

Background: Respiratory motions may cause artifacts on positron emission tomography (PET) images that degrade image quality and quantification accuracy. This study aimed to evaluate the effect of a respiratory motion-corrected image reconstruction (MCIR) algorithm on image quality and tumor quantification compared with nongated/nonmotion-corrected reconstruction. Methods: We used a phantom consisting of 5 motion spheres immersed in a chamber driven by a motor. The spheres and the background chamber were filled with 18F solution at a sphere-to-background ratio of 5:1. We enrolled 42 and 16 patients undergoing 2-deoxy-2-[18F]fluoro-D-glucose {2-[18F]FDG} and 68Ga-labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-Nal3-octreotide {[68Ga]Ga-DOTA-NOC} PET/computed tomography (CT) from whom 74 and 30 lesions were segmented, respectively. Three reconstructions were performed: data-driven gating-based motion correction (DDGMC), external vital signal module-based motion correction (VSMMC), and noncorrection reconstruction. The standardized uptake values (SUVs) and the volume of the spheres and the lesions were measured and compared among the 3 reconstruction groups. The image noise in the liver was measured, and the visual image quality of motion artifacts was scored by radiologists in the patient study. Results: In the phantom study, the spheres' SUVs increased by 26-36%, and the volumes decreased by 35-38% in DDGMC and VSMMC compared with the noncorrection group. In the 2-[18F]FDG PET patient study, the lesions' SUVs had a median increase of 10.87-12.65% while the volumes had a median decrease of 14.88-15.18% in DDGMC and VSMMC compared with those of noncorrection. In the [68Ga]Ga-DOTA-NOC PET patient study, the lesions' SUVs increased by 14.23-15.45%, and the volumes decreased by 19.11-20.94% in DDGMC and VSMMC. The image noise in the liver was equal between the DDGMC, VSMMC, and noncorrection groups. Radiologists found improved image quality in more than 45% of the cases in DDGMC and VSMMC compared with the noncorrection group. There was no statistically significant difference in SUVs, volumes, or visual image quality scores between DDGMC and VSMMC. Conclusions: MCIR improves tumor quantification accuracy and visual image quality by reducing respiratory motion artifacts without compromised image noise performance or elongated acquisition time in 2-[18F]FDG and [68Ga]Ga-DOTA-NOC PET/CT tumor imaging. The performance of DDG-driven MCIR is as good as that of the external device-driven solution.

Deep learning based on 68Ga-PSMA-11 PET/CT for predicting pathological upgrading in patients with prostate cancer.

Objectives: To explore the feasibility and importance of deep learning (DL) based on 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT in predicting pathological upgrading from biopsy to radical prostatectomy (RP) in patients with prostate cancer (PCa). Methods: In this retrospective study, all patients underwent 68Ga-PSMA-11 PET/CT, transrectal ultrasound (TRUS)-guided systematic biopsy, and RP for PCa sequentially between January 2017 and December 2022. Two DL models (three-dimensional [3D] ResNet-18 and 3D DenseNet-121) based on 68Ga-PSMA-11 PET and support vector machine (SVM) models integrating clinical data with DL signature were constructed. The model performance was evaluated using area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. Results: Of 109 patients, 87 (44 upgrading, 43 non-upgrading) were included in the training set and 22 (11 upgrading, 11 non-upgrading) in the test set. The combined SVM model, incorporating clinical features and signature of 3D ResNet-18 model, demonstrated satisfactory prediction in the test set with an AUC value of 0.628 (95% confidence interval [CI]: 0.365, 0.891) and accuracy of 0.727 (95% CI: 0.498, 0.893). Conclusion: A DL method based on 68Ga-PSMA-11 PET may have a role in predicting pathological upgrading from biopsy to RP in patients with PCa.

Phantom and clinical evaluation of the effect of a new Bayesian penalized likelihood reconstruction algorithm (HYPER Iterative) on 68Ga-DOTA-NOC PET/CT image quality.

BACKGROUND: Bayesian penalized likelihood (BPL) algorithm is an effective way to suppress noise in the process of positron emission tomography (PET) image reconstruction by incorporating a smooth penalty. The strength of the smooth penalty is controlled by the penalization factor. The aim was to investigate the impact of different penalization factors and acquisition times in a new BPL algorithm, HYPER Iterative, on the quality of 68Ga-DOTA-NOC PET/CT images. A phantom and 25 patients with neuroendocrine neoplasms who underwent 68Ga-DOTA-NOC PET/CT were included. The PET data were acquired in a list-mode with a digital PET/CT scanner and reconstructed by ordered subset expectation maximization (OSEM) and the HYPER Iterative algorithm with seven penalization factors between 0.03 and 0.5 for acquisitions of 2 and 3 min per bed position (m/b), both including time-of-flight and point of spread function recovery. The contrast recovery (CR), background variability (BV) and radioactivity concentration ratio (RCR) of the phantom; The SUVmean and coefficient of variation (CV) of the liver; and the SUVmax of the lesions were measured. Image quality was rated by two radiologists using a five-point Likert scale. RESULTS: The CR, BV, and RCR decreased with increasing penalization factors for four "hot" spheres, and the HYPER Iterative 2 m/b groups with penalization factors of 0.07 to 0.2 had equivalent CR and superior BV performance compared to the OSEM 3 m/b group. The liver SUVmean values were approximately equal in all reconstruction groups (range 5.95-5.97), and the liver CVs of the HYPER Iterative 2 m/b and 3 m/b groups with the penalization factors of 0.1 to 0.2 were equivalent to those of the OSEM 3 m/b group (p = 0.113-0.711 and p = 0.079-0.287, respectively), while the lesion SUVmax significantly increased by 19-22% and 25%, respectively (all p < 0.001). The highest qualitative score was attained at a penalization factor of 0.2 for the HYPER Iterative 2 m/b group (3.20 ± 0.52) and 3 m/b group (3.70 ± 0.36); those scores were comparable to or greater than that of the OSEM 3 m/b group (3.09 ± 0.36, p = 0.388 and p < 0.001, respectively). CONCLUSIONS: The HYPER Iterative algorithm with a penalization factor of 0.2 resulted in higher lesion contrast and lower image noise than OSEM for 68Ga-DOTA-NOC PET/CT, allowing the same image quality to be achieved with less injected radioactivity and a shorter acquisition time.

177Lu-PSMA-I&T Radioligand Therapy for Treating Metastatic Castration-Resistant Prostate Cancer: A Single-Centre Study in East Asians.

Purpose: There is increasing evidence for convincing efficacy and safety of 177Lu-labled prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (PRLT) for metastatic castration-resistant prostate cancer (mCRPC). However, data are not available regarding the feasibility of 177Lu-labled PSMA-targeted RLT in East Asians. The present study summarized the first experience with 177Lu-PSMA-I&T therapy for mCRPC in China. Methods: Forty consecutive patients with mCRPC were enrolled from December 2019 to September 2021. Eligible patients received 177Lu-PSMA-I&T RLT at intervals of 8-12 weeks. Toxicity was assessed based on standardized physicians' reports and the Common Toxicity Criteria for Adverse Events criteria. Response to PRLT was evaluated according to the changes of prostate specific antigen (PSA) response and imaging response. Quality of life (QOL), Karnofsky performance status (KPS) and pain (visual analogue scale, VAS) were also evaluated. The impacts of baseline parameters on the therapeutic effects were explored by univariate and multivariate logistic regression analyses. Results: All patients underwent a total of 86 cycles of 177Lu-PSMA-I&T (range: 1-5 cycles) with dosages of 3.70-14.43GBq per cycle, with a median of 8 months followed up. Six patients (15%) developed mild reversible xerostomia during follow-up, and 28 patients (70%) experienced grade 1-4 bone marrow dysfunction. Changes in PSA were assessed after therapy, accompanied by the partial response (PR) in 25 patients (62.5%), the stable disease (SD) in 5 patients (12.5%), and the progressive disease (PD) in 10 patients (25%), respectively. QOL, KPS (%) and VAS scores were improved significantly due to treatment (P<0.05). Overweight and elevated AST, ALP, and LDH were associated with poor outcomes. Conclusions: 177Lu-PSMA-I&T achieves the favourable response and well tolerance in mCRPC, which associates with not only PSA decline but also with tumor remission including lymphadenopathy and bone metastasis. We also find that patients with overweight and high AST, ALP, and LDH should be cautious to undergo the PRLT. Large-cohort studies are warranted to confirm the initial findings and elucidate the survival benefit of the treatment.

Small lesion depiction and quantification accuracy of oncological 18F-FDG PET/CT with small voxel and Bayesian penalized likelihood reconstruction.

BACKGROUND: To investigate the influence of small voxel Bayesian penalized likelihood (SVB) reconstruction on small lesion detection compared to ordered subset expectation maximization (OSEM) reconstruction using a clinical trials network (CTN) chest phantom and the patients with 18F-FDG-avid small lung tumors, and determine the optimal penalty factor for the lesion depiction and quantification. METHODS: The CTN phantom was filled with 18F solution with a sphere-to-background ratio of 3.81:1. Twenty-four patients with 18F-FDG-avid lung lesions (diameter < 2 cm) were enrolled. Six groups of PET images were reconstructed: routine voxel OSEM (RVOSEM), small voxel OSEM (SVOSEM), and SVB reconstructions with four penalty factors: 0.6, 0.8, 0.9, and 1.0 (SVB0.6, SVB0.8, SVB0.9, and SVB1.0). The routine and small voxel sizes are 4 × 4 × 4 and 2 × 2 × 2 mm3. The recovery coefficient (RC) was calculated by dividing the measured activity by the injected activity of the hot spheres in the phantom study. The SUVmax, target-to-liver ratio (TLR), contrast-to-noise ratio (CNR), the volume of the lesions, and the image noise of the liver were measured and calculated in the patient study. Visual image quality of the patient image was scored by two radiologists using a 5-point scale. RESULTS: In the phantom study, SVB0.6, SVB0.8, and SVB0.9 achieved higher RCs than SVOSEM. The RC was higher in SVOSEM than RVOSEM and SVB1.0. In the patient study, the SUVmax, TLR, and visual image quality scores of SVB0.6 to SVB0.9 were higher than those of RVOSEM, while the image noise of SVB0.8 to SVB1.0 was equivalent to or lower than that of RVOSEM. All SVB groups had higher CNRs than RVOSEM, but there was no difference between RVOSEM and SVOSEM. The lesion volumes derived from SVB0.6 to SVB0.9 were accurate, but over-estimated by RVOSEM, SVOSEM, and SVB1.0, using the CT measurement as the standard reference. CONCLUSIONS: The SVB reconstruction improved lesion contrast, TLR, CNR, and volumetric quantification accuracy for small lesions compared to RVOSEM reconstruction without image noise degradation or the need of longer emission time. A penalty factor of 0.8-0.9 was optimal for SVB reconstruction for the small tumor detection with 18F-FDG PET/CT.

Dosimetry of 177Lu-DOTATOC first circle treatment in patients with advanced metastatic neuroendocrine tumors: A pilot study in China.

First cycle dosimetry calculation of 177Lu-DOTATOC (single activity:1.59-3.49 GBq) was carried out in eight patients with advanced neuroendocrine tumors (NETs) who underwent whole-body planar (0.5, 24, 48, 72 h) and SPECT/CT scans (24 h). Focal uptake of 177Lu-DOTATOC was found in primary and metastatic tumors. Organs with the highest absorbed doses per injected activity were tumors (1.293 ± 0.862 mGy/MBq) and spleen (0.461 ± 0.408 mGy/MBq), while low absorbed doses were observed in kidneys (0.384 ± 0.112 mGy/MBq) and bone marrow (0.0297 ± 0.0123 mGy/MBq). 177Lu-DOTATOC is safe, well-tolerated and appropriate in Chinese NETs patients for PRRT.

Use of Chromogranin A for Monitoring Patients With Pancreatic Neuroendocrine Neoplasms.

OBJECTIVE: We aimed to assess the role of serum chromogranin A (CgA) in monitoring disease status and treatment response in patients with pancreatic neuroendocrine neoplasms (pNENs). METHODS: We included posttherapy pNENs patients with measured serum CgA levels who underwent 68Ga-labeled tetraazacyclododecanetetraacetic acid-peptide positron emission tomography (PET) imaging between April 2017 and January 2020. Serum CgA levels were determined by enzyme-linked immunosorbent assay. Tumor response was assessed according to the PET response evaluation criteria in solid tumors. RESULTS: Seventy-seven patients with 101 events were included in this study. Serum CgA levels were significantly higher in patients with active disease and metastasis. The optimal cutoff values for CgA for active and metastatic pNENs diagnosis after treatment were 52.39 (77.8% sensitivity, 80.7% specificity) and 60.18 ng/mL (73.9% sensitivity, 73.1% specificity), respectively. Based on 18 patients with serial CgA measurements and PET imaging, the optimal changes in CgA levels for predicting disease remission and progression were a 28.5% decrease (71.4% sensitivity, 88.2% specificity) and a 21.0% increase (100.0% sensitivity, 75.0% specificity), respectively. CONCLUSIONS: We concluded that serum CgA levels are associated with disease status and treatment response and may thus provide a helpful biomarker for the monitoring and clinical management of patients with pNENs.

[99mTc]Tc-Galacto-RGD2 integrin αvß3-targeted imaging as a surrogate for molecular phenotyping in lung cancer: real-world data.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) are beneficial in patients with lung cancer. We explored the clinical value of [99mTc]Tc-Galacto-RGD2 single-photon emission computed tomography (SPECT/CT) in patients with lung cancer, integrin αvß3 expression, and neovascularization in lung cancer subtypes was also addressed. METHODS: A total of 185 patients with lung cancer and 25 patients with benign lung diseases were enrolled in this prospective study from January 2013 to December 2016. All patients underwent [99mTc]Tc-Galacto-RGD2 imaging. The region of interest was drawn around each primary lesion, and tumour uptake of [99mTc]Tc-Galacto-RGD2 was expressed as the tumour/normal tissue ratio(T/N). The diagnostic efficacy was evaluated by receiver operating characteristic curve analysis. Tumour specimens were obtained from 66 patients with malignant diseases and 7 with benign disease. Tumour expression levels of αvß3, CD31, Ki-67, and CXCR4 were further analysed for the evaluation of biological behaviours. RESULTS: The lung cancer patients included 22 cases of small cell lung cancer (SCLC), 48 squamous cell carcinoma (LSC), 97 adenocarcinoma (LAC), and 18 other types of lung cancer. The sensitivity, specificity, and accuracy of [99mTc]Tc-Galacto-RGD2 SPECT/CT using a cut-off value of T/N ratio at 2.5 were 91.89%, 48.0%, and 86.67%, respectively. Integrin αvß3 expression was higher in non-SCLC compared with SCLC, while LSC showed denser neovascularization and higher integrin αvß3 expression. Integrin αvß3 expression levels were significantly higher in advanced (III, IV) than early stages (I, II). However, there was no significant correlation between tumour uptake and αvß3 expression. CONCLUSIONS: [99mTc]Tc-Galacto-RGD2 SPECT/CT has high sensitivity but limited specificity for detecting primary lung cancer, integrin expression in the tumour vessel and tumour cell membrane contributes to the tumour uptake.

Impact of total variation regularized expectation maximization reconstruction on the image quality of 68Ga-PSMA PET: a phantom and patient study.

OBJECTIVES: To investigate the impact of total variation regularized expectation maximization (TVREM) reconstruction on the image quality of 68Ga-PSMA-11 PET/CT using phantom and patient data. METHODS: Images of a phantom with small hot sphere inserts and 20 prostate cancer patients were acquired with a digital PET/CT using list-mode and reconstructed with ordered subset expectation maximization (OSEM) and TVREM with seven penalisation factors between 0.01 and 0.42 for 2 and 3 minutes-per-bed (m/b) acquisition. The contrast recovery (CR) and background variability (BV) of the phantom, image noise of the liver, and SUVmax of the lesions were measured. Qualitative image quality was scored by two radiologists using a 5-point scale (1-poor, 5-excellent). RESULTS: The performance of CR, BV, and image noise, and the gain of SUVmax was higher for TVREM 2 m/b groups with the penalization of 0.07 to 0.28 compared to OSEM 3 m/b group (all p < 0.05). The image noise of OSEM 3 m/b group was equivalent to TVREM 2 and 3 m/b groups with a penalization of 0.14 and 0.07, while lesions' SUVmax increased 15 and 20%. The highest qualitative score was attained at the penalization of 0.21 (3.30 ± 0.66) for TVREM 2 m/b groups and the penalization 0.14 (3.80 ± 0.41) for 3 m/b group that equal to or greater than OSEM 3 m/b group (2.90 ± 0.45, p = 0.2 and p < 0.001). CONCLUSIONS: TVREM improves lesion contrast and reduces image noise, which allows shorter acquisition with preserved image quality for PSMA PET/CT. ADVANCES IN KNOWLEDGE: TVREM reconstruction with optimized penalization factors can generate higher quality PSMA-PET images for prostate cancer diagnosis.

A preliminary study of imaging paclitaxel-induced tumor apoptosis with (99)Tc(m)-His10-Annexin V.

BACKGROUND: In tumors the process of apoptosis occurs over an interval of time after chemotherapy. It is important to determine the best time for detecting apoptosis by in vivo imaging. In this study, we evaluated the dynamics and feasibility of imaging non-small cell lung cancer (NSCLC) apoptosis induced by paclitaxel treatment using a (99)Tc(m)-labeled Annexin V recombinant with ten consecutive histidines (His10-Annexin V) in a mouse model. METHODS: (99)Tc(m)-His10-Annexin V was prepared by one step direct labeling; radio-chemical purity (RCP) and radio-stability was tested. The binding of (99)Tc(m)-His10-Annexin V to apoptotic cells was validated in vitro using camptothecin-induced Jurkat cells. In vivo bio-distribution was determined in mice by dissection. The human H460 NSCLC tumor cell line (H460) tumor-bearing mice were treated with intravenous paclitaxel 24, 48 and 72 hours later. (99)Tc(m)-His10-Annexin V was injected intravenously, and planar images were acquired at 2, 4 and 6 hours post-injection on a dual-head gamma camera fitted with a pinhole collimator. Tumor-to-normal tissue ratios (T/NT) were calculated by ROI analysis and they reflected specific binding of (99)Tc(m)-His10-Annexin V. Mice were sacrificed after imaging. Caspase-3, as the apoptosis detector, was determined by flow cytometry, and DNA fragmentation was analyzed by the terminal deoxynucleotidytransferase mediated dUTP nick-end labeling (TUNEL) assay. Nonspecific accumulation of protein was estimated using bovine serum albumin (BSA). The imaging data were correlated with TUNEL-positive nuclei and caspase-3 activity. RESULTS: (99)Tc(m)-His10-Annexin V had a RCP > 98% and high stability 2 hours after radio-labeling, and it could bind to apoptotic cells with high affinity. Bio-distribution of (99)Tc(m)-His10-Annexin V showed predominant uptake in kidney, relatively low uptake in myocardium, liver and gastrointestinal tract, and rapid clearance from blood and kidney was observed. The T/NT was significantly increased after paclitaxel treatment, whereas it was low in untreated tumors (T/NT = 1.43 ± 0.18). The %ID/g activity in Group 2 (24 hours), Group 3 (48 hours) and Group 4 (72 hours) after treatment was 2.55 ± 0.73, 3.35 ± 1.10, and 3.4 ± 0.96, respectively. Whereas in the non-treated group, Group 1, %ID/g was 1.10 ± 0.18. The radiotracer uptake was positively correlated to the apoptotic index (r = 0.852, P < 0.01), as well as caspase-3 activity (r = 0.816, P < 0.01). CONCLUSION: This study addresses the dynamics and feasibility of imaging non-small cell lung tumor apoptosis using (99)Tc(m)- His10-Annexin V.

Study on bone density at various skeletal sites for the diagnosis of primary osteoporosis.

The objective of this study was to evaluate the diagnostic value of bone density changes in lumbar vertebrae and femoral necks in patients with primary osteoporosis (OP) at various ages. Dual-energy X-ray absorptiometry (DXA) scans were performed on patients who had their primary visits between March 2008 and February 2009. The bone mineral density (BMD) of the lumbar vertebrae 1-4 (L1-L4) in anteroposterior projection and the proximal femoral neck in lateral projection were measured. If the BMD values (T score) of any site is -2.5 or less (T ≤ -2.5), the patients were diagnosed as primary OP, and the T scores were statistically analyzed. The 81 patients who had lumbar vertebrae with a T ≤ -2.5 led to a positive rate of 80.1 % in the diagnosis of primary OP; the 47 patients who had femoral neck with a T ≤ -2.5 gave a positive rate of 47.0 %. The patients with type I or type II primary OP were divided into two age groups of ≤70 and ≥71 years old. The comparison of lumbar spine T score values did not show significant statistical difference (P > 0.05) between the age groups, while the result of the femoral necks revealed significant difference between the two groups (P < 0.001). In diagnosis of primary OP, anteroposterior lumbar spine offers a significantly higher detection rate than that of the femoral neck, but to the patients older than 70, the measurement of femoral neck may generate higher detection rate. It is more sensitive to measure lumbar trabecular bone, especially to the patients in early postmenopausal period. BMD in elderly patients may falsely increase with age, attention should be paid to the determination of the hip bone mass.

[Technetium-99m labeled synaptotagmin I C2A detection of paclitaxel-induced apoptosis in non-small cell lung cancer].

UNLABELLED: Objective To evaluate the efficacy of 99mTc-labeled C2A probe in detection of apoptosis of non-small cell lung cancer (NSCLC) cells after chemotherapy. METHODS: Imaging studies were performed in NSCLC H460-bearing mice. The mice were divided into 2 groups: the paclitaxel-treated group and control group. 99mTc-C2A was injected intravenously at 12, 24, 48 and 72 h after chemotherapy. Images were acquired at 3 h and 6 h after injection using a pinhole collimator. The regions of interest (ROI) were drawn in tumor area and contralateral nomal tissue, and the ratio of T/NT were caculated. The tumor sections were stained by HE and TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-nick-end labeling) staining to confirm the presence of apoptosis. Activated caspase-3 was also analyzed with flow cytometry. RESULTS: Little uptake of 99mTc-C2A was found in baseline images, but tumor uptake increased very much after chemotherapy, the T/NT ratio was 1.79 +/- 0.34, 2.23 +/- 0.33 and 2.78 +/- 0.34, respectively. The T/NT ratio of control was 1.48 +/- 0.23. Tumor uptake (% ID/g) of 99mTc-C2A in chemotherapy groups were 2.82 +/- 0.90, 3.13 +/- 0.48 and 3.52 +/- 1.18, respectively. Tumor uptake (% ID/g) in the control group was 1.21 +/- 0.51. It in paclitaxel-treatment groups were 2.82 +/- 0.90, 3.13 +/- 0.48 and 3.51 +/- 1.18, respectively, significantly higher than that in untreated mice. Furthermore, the uptake of 99mTc-C2A correlated well with apoptotic index (r = 0.56, P < 0.01), and activated caspase-3 (r = 0.59, P < 0.01). CONCLUSION: Our preliminary results demonstrated that 99mTc-C2A imaging in vivo for detection of cell death in solid tumors is feasible and well correlated with TUNEL staining and activated caspase-3. The C2A holds promise and warrants further development as a molecular probe to early predict cancer treatment efficacy.

[Application of technetium-99m labelled sandostatin Somatostatin receptor imaging in the detection of lung cancer].

OBJECTIVE: To evaluate the clinical value of (99)Tc(m)-sandostatin receptors imaging ((99)Tc(m)-sandostatin) in detection of lung tumors in comparison with fludeoxyglucose F18 dual head coincidence imaging ((18)F-FDG DHC). METHODS: Fifty-six consecutive patients (40 men, 16 women; mean age: 62 years, range 35 - 80 years) with pulmonary neoplasm were referred for evaluation. All underwent sandostatin scintigraphy using hybrid SPECT/CT. (18)F-FDG DHC imaging was also performed in 23 patients using the same camera. The tumor uptake of (99)Tc(m)-sandostatin and (18)F-FDG DHC were measured respectively and expressed as the ratio of T/Nr and T/Nm. Final clinical diagnosis was confirmed by histopathological study. RESULTS: Out of 56 cases, 46 were confirmed to be malignant and 10 benign. The sensitivity, specificity and accuracy of (99)Tc(m)-sandostatin in diagnosis of lung cancer were 95.7%, 90.0%, 94.6%, respectively. The positive predictive value (PPR) was 97.8%, and the negative predictive value (NPR) was 81.8%. In the 23 patients underwent both methods, the sensitivity, specificity and accuracy of (18)F-FDG DHC were 100%, 60.0%, 82.6%, respectively; the PPR was 76.5%, and the NPR 100%. Out of 13 patients with malignant neoplasms, 6 patients had regional lymph node metastasis, and all of 10 abnormal lymph nodules showed high uptake of FDG, while (99)Tc(m)-sandostatin imaging only 2 regional metastasized lymph nodes in one patient. T/N(r) and T/N(m) were 3.15 +/- 1.30, and 10.61 +/- 4.35 respectively. There was no relationship between sandostatin uptake and glucose metabolism. CONCLUSION: (99)Tc(m)-sandostatin scintigraphy is a promising noninvasive imaging technique for detection of the primary tumor of lung cancer but of limited value in the detection of lymph node metastasis.