Clinical value of PET/CT with carbon-11 4DST in the evaluation of malignant and benign lung tumors.

OBJECTIVES: The aim of this study was to assess the clinical value of [11C]4DST uptake in patients with lung nodules, including benign and malignant tumors, and to assess the correlation between [11C]4DST uptake and proliferative activity of tumors in comparison with [18F]FDG uptake. METHODS: Twenty-six patients (22 males and 4 females, mean age of 65.5-year-old) were analyzed in this prospective study. Patients underwent [11C]4DST and [18F]FDG PET/CT imaging on the same day. Diagnosis of each lung nodule was confirmed by histopathological examination of tissue specimens at surgery, or during clinical follow-up after the PET/CT studies. To assess the utility of the semi-quantitative evaluation method, the SUVmax was calculated of [11C]4DST and [18F]FDG uptake by the lesion. Proliferative activities of each tumor as indicated by the immunohistochemical Ki-67 index was also estimated using surgical specimens of patients. Then the relationship between the SUVmax of both PET/CT and the Ki-67 index was examined. Furthermore, the relationship between the uptake of [11C]4DST or [18F]FDG and the histopathological findings, the clinical stage, and the clinical outcome of patients were also assessed. RESULTS: There was a positive linear relationship between the SUVmax of [11C]4DST images and the Ki-67 index (Correlation coefficients = 0.68). The SUVmax of [11C]4DST in the 26 lung nodules were 1.65 ± 0.40 for benign lesions, 3.09 ± 0.83 for adenocarcinomas (P < 0.001 between benign and adenocarcinoma), and 2.92 ± 0.58 for SqCCs (P < 0.001 between benign and SqCC). Whereas, the SUVmax of [18F]FDG were 2.38 ± 2.27 for benign lesions, 6.63 ± 4.24 for adenocarcinomas (n.s.), and 7.52 ± 2.84 for SqCCs (n.s.). The relationship between TNM tumor stage and the SUVmax of [11C]4DST were 2.54 ± 0.37 for T1, 3.48 ± 0.57 for T2, and 4.17 ± 0.72 for T3 (P < 0.005 between T1 and T2, and P < 0.001 between T1 and T3). In comparison with the TNM pathological stage, SUVmax of [11C]4DST were 2.63 ± 0.49 for stage I, 3.36 ± 0.23 for stage II, 3.40 ± 1.12 for stage III, and 4.65 for stage IV (P < 0.05 between stages I and II). In comparison of the clinical outcome, the SUVmax of [11C]4DST were 2.72 ± 0.56 for the no recurrence (No Rec.) group, 3.10 ± 0.33 for the recurrence-free with adjuvant chemotherapy after the surgery (the No Rec. Adjv. CTx. group) and 4.66 ± 0.02 for the recurrence group (Rec. group) (P < 0.001 between the No Rec and Rec. groups, and P < 0.005 between the No Rec. Adjv. CTx. and Rec. groups). CONCLUSIONS: PET/CT with [11C]4DST is as feasible for imaging of lung tumors as [18F]FDG PET/CT. For diagnosing lung tumors, [11C]4DST PET is useful in distinguishing benign nodules from malignancies. [11C]4DST uptake in lung carcinomas is correlated with the proliferative activity of tumors, indicating a promising noninvasive PET imaging of DNA synthesis in malignant lung tumors.

Diagnostic performance of a computer-assisted diagnostic system: sensitivity of BONENAVI for bone scintigraphy in patients with disseminated skeletal metastasis is not so high.

PURPOSE: Bone scintigraphy (BS) of disseminated skeletal metastasis is sometimes misinterpreted as normal. The use of computer-assisted diagnosis (CAD) may resolve this problem. We investigated the performance of a CAD system, BONENAVI, in the diagnosis of disseminated skeletal metastasis. METHODS: Cases of disseminated skeletal metastasis were selected from a BS log. These patients' BSs were analyzed by BONENAVI to obtain an artificial neural network (ANN) and bone scan index (BSI). Clinical features (type of primary cancer, CT type, and BS type) were compared with the BONENAVI (ANN and BSI) results. The BS findings (diffuse increased axial skeleton uptake, inhomogeneity of uptake, proximal extremity contrast, and degree of renal uptake) and ANN or BSI were evaluated. Then, negative ANN patients were presented. RESULTS: Fifty-four patients were diagnosed as having disseminated skeletal metastasis. Regarding the primary cancers, 12 had prostate cancer, 16 gastric cancers, 16 breast cancers, and 10 miscellaneous cancers. Total sensitivity of ANN (≥ 0.5) was 76% (41/54). ANN values correlated with the BS type among clinical features. Diffuse increased axial skeleton uptake was mostly correlated with ANN of the BS findings. CONCLUSION: The BONENAVI CAD system was partially helpful in diagnosing disseminated skeletal metastasis, but the sensitivity of BONENAVI was not sufficient and underestimated the disseminated skeletal metastasis. Further improvement of this CAD system is necessary to improve the detectability of disseminated skeletal metastasis.

Comparison of vascularized supraclavicular lymph node transfer and lymphaticovenular anastomosis for advanced stage lower extremity lymphedema.

BACKGROUND: Vascularized lymph node transfer has become a popular surgical option to improve lower extremity lymphedema (LEL), although potential donor sites are limited. The free supraclavicular flap with deep cervical lymph nodes has been recently associated with a minimal risk of secondary lymphedema caused by donor site dissection. However, the effectiveness of this procedure has not yet been evaluated. METHODS: Vascularized supraclavicular lymph node transfer (VSLNT) was performed for patients with International Society of Lymphology late stage II or more severe LEL. The results were compared with lymphaticovenular anastomosis (LVA) performed for patients with the same stages of severity. To evaluate improvement in lymphatic function, indocyanine green lymphography and lymphoscintigraphy were performed. RESULTS: Vascularized supraclavicular lymph node transfer was performed in 13 limbs of 13 patients. The results were compared with 43 limbs of 33 patients who underwent multiple LVA. No severe complications were observed in either group. Improvement in lymphatic function, as measured by the LEL index, was 26.5 ± 4.4 and 21.2 ± 2.0 in the VSLNT and LVA groups, respectively. Lymphatic function was improved in 7 cases in the VSLNT group and 10 cases in the LVA group. CONCLUSIONS: Vascularized supraclavicular lymph node transfer is an effective technique for the treatment of advanced stage LEL. Lymphaticovenular anastomosis is also effective, but to a lesser degree than VSLNT. However, LVA is less invasive and requires a shorter hospital stay.

The relationship between skeletal-related events and bone scan index for the treatment of bone metastasis with breast cancer patients.

The aim of the present study was to investigate the relationships between the automated bone scan index (aBSI) and skeletal-related events (SRE) in breast cancer patients with bone metastasis. A computer-aided software (BONENAVI™) that was developed using an Artificial Neural Network (Artificial Neural Network) was used for the present analysis. Forty-five patients diagnosed with bone metastasis due to breast cancer from April 2005 through March 2013 were retrospectively analyzed. Before and after the time of initial treatment, aBSI, Artificial Neural Network score, and hotspot number were calculated, and the relationships between these scores and SRE were analyzed. Twenty cases showed decreased (improved) aBSI values after initial treatment (Group A), and 25 cases showed unchanged/increased (worsened) aBSI values (Group B). Chi-square analysis revealed a significant difference in incident numbers of SRE between the two groups--one case in Group A and 12 in Group B (P<0.001). Event-free survival was significantly shorter in Group B (hazard ratio: 8.31, 95% CI: 1.33-12.14, log-rank test; P<0.05). The groups were also divided by the results of 2 radiologists' visual scan interpretations, and no significant differences were shown in the number of SRE (P=0.82, P=0.10). When correlation analyses were performed between aBSI and bone metabolic or tumor markers, alkaline phosphatase was significantly correlated with aBSI at the time of initial treatment (R=0.69, P<0.05). In conclusion, aBSI is proposed as a useful and objective imaging biomarker in the detection of breast-cancer patients with bone metastasis at high risk of SRE.

Thyroid remnant ablation using 1,110 MBq of I-131 after total thyroidectomy: regulatory considerations on release of patients after unsealed radioiodine therapy.

OBJECTIVES: This study was undertaken to measure the radiation exposure level of caregivers following outpatient NaI (I-131) 1,110 MBq therapy for remnant thyroid ablation after total thyroidectomy in patients with differentiated thyroid cancer, and to evaluate the influence of activities of daily living on radiation exposure level, with the goal of proposing an optimum method of I-131 therapy. METHODS: The study included 37 patients with differentiated thyroid cancer, who had undergone total thyroidectomy and received outpatient based remnant thyroid ablation using NaI (I-131) 1,110 MBq, who were satisfying the following requirements: (1) patients who have no evidence of distant metastases, (2) whose living environments were appropriate for outpatient I-131 (1,110 MBq) therapy, and (3) patients who gave written informed consent. The dose rate at a distance of 1 m from the body surface of the patient at the moment of release was measured using survey meters of the GM type or ionization chamber type. The dose level for the caregiver was measured with a personal dosimeter in all cases. RESULTS: The dose rate at a distance of 1 m from the patient's body surface 1 h after I-131 administration was in the range of 29-115 µSv/h (mean 63.8 µSv/h). The 7-day cumulative effective dose of caregivers was 0.11 ± 0.08 mSv, on an average, in 34 dosimeters. In 31 of 34 dosimeters, cumulative effective dose of caregivers was below 0.2 mSv. Dose levels exceeding 0.2 mSv were recorded in 3 cases (0.21, 0.35 and 0.43 mSv in one case each). These results suggest that the exposure level of family members (caregiver and others) was minimal and is lower than the radiation levels affecting human environments. CONCLUSION: Outpatient-based remnant thyroid ablation with I-131 (1,110 MBq) performed after total thyroidectomy in patients with differentiated thyroid cancer is safe if applied in accordance with the appropriate supervision and guidance by experts with certain qualifications.

[Guidelines for radio-iodine (131I) therapy in Graves' disease and thyroid cancer].

Radio-iodine (131I) therapy has been using in Graves' disease and well differentiated thyroid cancer. The rules of control in the discharge from radio-isotope hospital were notified in 1999 in Japan. Guideline of the 131I therapy in Graves' disease and thyroid cancer were prepared by sub-group of Japanese Society of Nuclear Medicine.

Correlation between angiogenesis and reduction ratio measured using 201Tl chloride single photon emission computed tomography in patients with oral cavity squamous cell carcinoma.

OBJECTIVE: The aim of this study is to examine the correlation between tumor angiogenesis and response to preoperative radiotherapy evaluated using 201Tl single photon emission computed tomography (Tl SPECT) in oral cavity squamous cell carcinoma (SCC). METHODS: Tl SPECTs before and after preoperative radiotherapy were obtained from 11 patients diagnosed with SCC in oral cavity. Regions of interest were set around the tumor and scalp respectively, and the ratio of mean counts in the tumor to those in the scalp was calculated (T/N). Immunohistochemical staining for investigating microvessel density of pre-treatment biopsy specimen was performed using CD31 monoclonal antibody. We compared microvessel density with semi-quantitative parameters obtained using Tl SPECT (T/N at pre- an post-treatment, reduction ratio) and prognosis. RESULTS: The subgroup with higher microvessel density showed a significantly higher reduction ratio than the one with lower microvessel density. Regarding prognosis, the subgroup with locoregional recurrent disease exhibited a significantly higher microvessel density than the one without recurrence. CONCLUSIONS: In SCC of the oral cavity, there was a significant correlation between microvessel density and response to preoperative radiotherapy. Namely, it was revealed that change of 201Tl uptake after preoperative radiotherapy correlated with tumor angiogenesis of oral cavity SCC.

Evaluation of mandibular invasion by head and neck cancers using 99mTc-methylene diphosphonate or 99mTc-hydroxymethylene diphosphonate and 201Tl chloride dual isotope single photon emission computed tomography.

Whether a patient with head and neck cancer has mandibular invasion or not is important in determining the method of resection surgery. But, no modality is adequately reliable when used alone in the evaluation of mandibular invasion. Therefore, to more accurately diagnose mandibular invasion in head and neck cancer, we used a new modality, namely, 99mTc methylene diphosphonate (MDP) or 99mTc hydroxymethylene diphosphonate (HMDP) and 201Tl chloride dual isotope single photon emission computed tomography (Tc/Tl SPECT). The aim of this study is to disclose the usefulness of Tc/Tl SPECT in the assessment of mandibular invasion by head and neck cancers. 99mTc-MDP or -HMDP SPECT (Tc SPECT)s and 201Tl chloride SPECT (Tl SPECT)s were performed in 34 patients with suspected mandibular involvement of head and neck cancer. Thirty of 34 cases underwent both TcMTl SPECT and CT examination. Tc/Tl SPECT fusion images were obtained using the Automatic Registration Tool (ART, TOSHIBA, Japan) system. In the diagnosis of mandibular invasion on Tc/Tl SPECT fusion images, a problem was that the range of Tc and Tl uptake was changed by the condition of display used in the reconstruction and expression of the images. Then, prior to clinical evaluation, to reveal the most appropriate upper window level for display, a phantom study was performed. In a clinical study, the upper window level was set at 40 or 50%, which were verified to be the proper values in the preliminary study. The diagnostic accuracy obtained using Tc SPECT, TcMTl SPECT and CT was compared with the histopathological findings. Tc/Tl SPECT at 40 and 50% upper window level had higher specificity, accuracy, and positive predictive value (73.3%, 85.3%, 81.8%) than Tc SPECT alone (21.4%, 67.6%, 64.5%) and higher sensitivity and negative predictive value (94.7%, 91.7%) than CT (70.6%, 72.2%) for detecting mandibular invasion. Tc/Tl SPECT was a useful diagnostic procedure for the assessment of mandibular invasion by head and neck cancers.

Semi-quantitative assessment of oral cavity squamous cell carcinoma using 201Tl SPECT for evaluating effectiveness of preoperative radiotherapy.

The aim of this study is to reveal the usefulness of semi-quantitative assessment using 201Tl chloride (Tl) single photon emission computed tomography (SPECT) (Tl SPECT) to evaluate the effectiveness of radiotherapy in 15 patients with oral cavity squamous cell carcinma (SCC). Fifteen patients were diagnosed with SCC by biopsy. All 15 patients enrolled in this study were planned to undergo preoperative radiotherapy with or without chemotherapy using carboplatin (CBDCA) and received reduction operation. Tl SPECTs were performed 15 minutes after intravenous administration of 111 MBq 201Tl chloride. Regions of Interest (ROI) were set up around tumor (T), and non-lesion (N) at the part of contralateral scalp at the height of the cerebellum. The ratios of mean counts in ROI of the tumor to those in non-lesion were measured as pre- and post-treatment T/N ratios (pre T/N, post T/N). Furthermore, reduction rate (RR) was obtained by calculating [(pre T/N - post T/N)/(pre T/ N)] x 100%. Each parameter (pre T/N, post T/N, and RR) was compared to histopathological grade of surgical specimen based on the Oboshi and Shimosato classification (grade I-IV). RR showed significantly higher values in grade III and IV than in grade I and II (p = 0.0008). In conclusion, semi-quantitative assessment using Tl SPECT, especially calculating RR, is useful to evaluate the effectiveness of preoperative radiotherapy.

Comparison of barium swallow, CT and thallium-201 SPECT in evaluating responses of patients with esophageal squamous cell carcinoma to preoperative chemoradiotherapy.

The aims of this study were to compare the results of thallium-201 (Tl-201) SPECT, barium swallow and CT in the assessment of the effect of preoperative chemoradiotherapy. This study consisted of 28 patients with advanced esophageal squamous cell carcinoma (AESCC) who underwent the three imaging modalities before and after preoperative chemoradiotherapy. The results were quantified using the bidimensional method for barium swallow and contrast-enhanced CT and the tumor-to-lung ratio for SPECT. The percent decrease in these quantitative values after therapy was defined as %Dba, %Dct and %Dtl respectively. The histological effect of the chemoradiotherapy was determined from the resected surgical specimen of the esophagus: grade 0, 100% viable tumor cells; grade 1a, 99-67%; grade 1b, 66-34%; grade 2, 33-1%; grade 3, no viable cells. A statistically significant difference of %Dtl between the subgroups of each grade was evident (p = 0.0433), whereas no significant differences were evident for %Dba (p = 0.1778) or %Dct (p = 0.7377). However, the overlap of %Dtl between these groups was marked. Although thallium-201 SPECT cannot be used to evaluate the therapeutic effect with acceptable accuracy, SPECT may be of additional value to barium swallow and CT in assessing the response of AESCC to preoperative chemoradiotherapy.

Extraosseous accumulation of bone scanning agents in malignant brain tumors: comparison to semi-quantitative evaluation with 99mTc SPECT/201Tl SPECT and histological findings.

Although 201Tl chloride (Tl) SPECT has been used in the differential diagnosis between recurrence of malignant brain tumor and necrosis after treatment, it is not generally recognized as a definite modality to distinguish them. We conducted a preliminary study using Tl SPECT and 99mTc-MDP or 99mTc-HMDP (Tc) SPECT because it has been said that extraosseous accumulation was caused by calcium deposits in necrotic tissues. In our study, for the purposes of clarifying the mechanism of extraosseous uptake and the correlation between extraosseous accumulation of bone-scanning agent and tumor viability in malignant brain tumors, we compared whether Tc uptake was correlated with the histopathological findings and further performed semi-quantitative evaluation between Tc SPECT and Tl SPECT. The correlation coefficients between the ratio of tumor to normal skull count obtained from Tc SPECT (Tc-T/N) and those of tumor to normal brain count (T/N) and to normal scalp count (T/S) both obtained from Tl SPECT were calculated. Using contrast enhanced CT (CE-CT) or contrast enhanced MRI (CE-MRI), 8 of 10 cases showed intensely ring-enhanced tumor with necrotic lesion. Histopathologically, 7 of 8 cases whose tumor had been resected before treatment had necrosis with increased vascularity or bleeding. Of the remaining 2 cases one case, malignant lymphoma had only hypervascularity by biopsy, while the other one was excluded for resection after treatment. Three of these 8 cases whose CE-CT or CE-MRI showed necrotic lesions exhibited Tc and Tl accumulations in the area corresponding to necrosis. In contrast, 2 showed no Tc nor Tl uptake. Tc-T/N had no significant correlation with any of early-, delayed-T/N or T/S. In conclusion, there was no significant correlation between Tc and Tl uptakes by malignant brain tumors in semi-quantitative evaluation.

False-positive CT and thallium-201 SPECT results in a patient with suspected lung cancer and mediastinal lymph node metastasis.

We describe a patient with a final diagnosis of inflammatory change in which combined imaging results were strongly suggestive of lung cancer with mediastinal lymph node metastases. The patient, who was suspected of having a pulmonary lesion on chest radiography performed at a local hospital, was referred to our hospital. Contrast-enhanced computed tomography (CT) of the chest showed a small-sized opacity in the left upper lung and multiple mediastinal nodules. The largest mediastinal nodule, depicted at a pretracheal region, was 22 mm in size. Thallium-201 single photon emission computed tomography (SPECT) showed increased uptake in these lesions, which exhibited no remarkable washout of the tracer, supportive of the diagnosis of lung cancer with mediastinal lymph node metastasis. However, bronchoscopic and mediastinoscopic biopsy revealed no malignant cells or reactive lymph nodes, respectively. Therefore, no surgical procedure was performed after the biopsy. The patient has done well without evidence of malignancy for 21 months. Radiologists should be careful in the differential diagnosis of benign and malignant lesions even with combined imaging modalities.

Will subareolar injection be a standard technique for sentinel lymph node biopsy?

BACKGROUND: Controversy surrounds the correct injection site of radioisotope (RI) and blue dye for sentinel node biopsy (SNB) in breast cancer, and there have been some reports on the advantages of subareolar (SA) injection. We carried out a study to assess whether SA injection is useful for all patients undergoing SNB. METHODS: In this prospective study, 20 patients with T1 or T2 tumors clinically node negative, were enrolled. Injection of 99mTc-phytate (0.5 mCi) was performed two times (3 to 5 days before surgery and the day of surgery) for each patient. The first RI injection was SA, and the second RI injection was subdermal (SD). The location and number of hot nodes were assessed by lymphoscintigraphy (LSG) and hand-held gamma probe. RESULTS: There were no patients in whom hot nodes on LSG were visualized in clearly different locations between the SA and SD injection sites. However, there were 2 patients in whom hot nodes were identified at different locations with a gamma probe. Seven patients had more hot nodes on LSG with SD injection than SA injection. Eight patients had a higher RI count of hot nodes by SD injection than SA injection. The mean RI count of hot nodes by SA injection was higher than that after SD injection. CONCLUSION: SA and SD lymphatic flow run into the same node in most patients, however, SD injection is more useful than SA injection in some patients. Though SA injection is a useful technique, it may not identify sentinel lymph nodes correctly in patients with multiple lesions or tumors in the upper outer quadrant.

Detection and chemoradiotherapeutic evaluation of advanced esophageal squamous cell carcinoma using gallium-67 SPET: a preliminary study.

About 20 years ago, gallium-67 planar scintigraphy was introduced for the evaluation of advanced esophageal squamous cell carcinoma (AESCC). Although single-photon emission tomography (SPET) is now available in many institutions, there have been no reports regarding the evaluation of AESCC using (67)Ga SPET. The aims of this preliminary study were to assess the potential of (67)Ga SPET for the detection of AESCC and to further evaluate whether (67)Ga SPET can predict the effect of preoperative chemoradiotherapy on AESCC. Thirty-eight patients with histologically proven AESCC (35 men and 3 women, mean age 62+/-6.9 years) underwent (67)Ga SPET before and after preoperative chemoradiotherapy. The histological response to the chemoradiotherapy was determined from a surgical specimen of the esophagus: grade 0, 100% viable tumor cells; grade 1a, 99%-67%; grade 1b, 66%-34%; grade 2, 33%-1%; grade 3, no viable cells. Thirty-seven out of 38 AESCCs (97.4%) were detected on pre-chemoradiotherapy SPET. In these 37 cancers, the tumor-to-lung ratio (TLRpre) was 3.5+/-2 (range 1.5-9.6). Post-chemoradiotherapy SPET exhibited positive results in 22 cancers, with a TLRpost of 1.8+/-0.4 (range 1.1-2.6). No patient exhibiting a pathologically complete response had a positive post-chemoradiotherapy SPET result, whereas 80% of patients with negative post-chemoradiotherapy SPET (12/15) results had residual tumor. The percent reduction rate was defined as (TLRpre-TLRpost)/TLRpre x100 and did not correlate with histological response grade ( P=0.5169 for Kruskal-Wallis test). These results suggest that (67)Ga SPET is a powerful tool for the detection of AESCC. However, (67)Ga SPET seems to be of little use in predicting the effects of preoperative chemoradiotherapy on AESCC. Further studies are warranted in order to further clarify the clinical usefulness of (67)Ga SPET in patients with AESCC.

Extraosseous accumulation of 99mTc phosphonate complexes in primary brain tumor evaluated with SPECT.

Although extraosseous accumulations of 99mTc phosphate complexes are phenomena which can often be seen, no case showing extraosseous accumulation to brain tumor on SPECT has been reported. We report here two cases of primary brain tumor showing extraosseous accumulation of 99mTc phosphate in bone SPECT. 201Tl SPECT also showed increased 201Tl uptake by the tumor. Comparing bone SPECT with 201Tl SPECT, the regions of abnormality of both SPECTs were very similar in the case of glioblastoma, but in the case of malignant lymphoma the region showing intense uptake of 99mTc-MDP was smaller than that on 201Tl SPECT. It was revealed that bone SPECT is more useful in the assessment of extraosseous accumulation to a primary brain tumor than conventional bone scintigraphy.