Usefulness of 18F-fluoride PET/CT in Breast Cancer Patients with Osteosclerotic Bone Metastases

Purpose

Bone metastasis is an important factor for the treatment and prognosis of breast cancer patients. Whole-body bone scintigraphy (WBBS) can evaluate skeletal metastases, and ¹⁸F-FDG PET/CT seems to exhibit high specificity and accuracy in detecting bone metastases. However, there is a limitation of ¹⁸F-FDG PET in assessing sclerotic bone metastases because some lesions may be undetectable. Recent studies showed that ¹⁸F-fluoride PET/CT is more sensitive than WBBS in detecting bone metastases. This study aims to evaluate the usefulness of ¹⁸F-fluoride PET/CT by comparing it with WBBS and ¹⁸F-FDG PET/CT in breast cancer patients with osteosclerotic skeletal metastases.

Materials and Methods

Nine breast cancer patients with suspected bone metastases (9 females; mean age ± SD, 55.6 ± 10.0 years) underwent ^99mTc-MDP WBBS, ¹⁸F-FDG PET/CT and ¹⁸F-fluoride PET/CT. Lesion-based analysis of five regions of the skeletons (skull, vertebral column, thoracic cage, pelvic bones and long bones of extremities) and patient-based analysis were performed.

Results

¹⁸F-fluoride PET/CT, ¹⁸F-FDG PET/CT and WBBS detected 49, 20 and 25 true metastases, respectively. Sensitivity, specificity, positive predictive value and negative predictive value of ¹⁸F-fluoride PET/CT were 94.2 %, 46.3 %, 57.7 % and 91.2 %, respectively. Most true metastatic lesions on ¹⁸F-fluoride PET/CT had osteosclerotic change (45/49, 91.8 %), and only four lesions showed osteolytic change. Most lesions on ¹⁸F-FDG PET/CT also demonstrated osteosclerotic change (17/20, 85.0 %) with three osteolytic lesions. All true metastatic lesions detected on WBBS and ¹⁸F-FDG PET/CT were identified on ¹⁸F-fluoride PET/CT.

Conclusion

¹⁸F-fluoride PET/CT is superior to WBBS or ¹⁸F-FDG PET/CT in detecting osteosclerotic metastatic lesions. ¹⁸F-fluoride PET/CT might be useful in evaluating osteosclerotic metastases in breast cancer patients.     

The use of 18F-fluoride and 18F-FDG PET scans to assess fracture healing in a rat femur model

Purpose Currently available diagnostic techniques can be unreliable in the diagnosis of delayed fracture healing in certain clinical situations, which can lead to increased complication rates and costs to the health care system. This study sought to determine the utility of positron emission tomography (PET) scanning with ¹⁸F-fluoride ion, which localizes in regions of high osteoblastic activity, and ¹⁸F-fluorodeoxyglucose (FDG), an indicator of cellular glucose metabolism, in assessing bone healing in a rat femur fracture model. Methods Fractures were created in the femurs of immunocompetent rats. Animals in group I had a fracture produced via a manual three-point bending technique. Group II animals underwent a femoral osteotomy with placement of a 2-mm silastic spacer at the fracture site. Fracture healing was assessed with plain radiographs, ¹⁸F-fluoride, and ¹⁸F-FDG PET scans at 1, 2, 3, and 4-week time points after surgery. Femoral specimens were harvested for histologic analysis and manual testing of torsional and bending strength 4 weeks after surgery. Results All fractures in group I revealed abundant callus formation and bone healing, while none of the nonunion femurs were healed via assessment with manual palpation, radiographic, and histologic evaluation at the 4-week time point. ¹⁸F-fluoride PET images of group I femurs at successive 1-week intervals revealed progressively increased signal uptake at the union site during fracture repair. In contrast, minimal tracer uptake was seen at the fracture sites in group II at all time points after surgery. Data analysis revealed statistically significant differences in mean signal intensity between groups I and II at each weekly interval. No significant differences between the two groups were seen using ¹⁸F-FDG PET imaging at any time point. Conclusion This study suggests that ¹⁸F-fluoride PET imaging, which is an indicator of osteoblastic activity in vivo, can identify fracture nonunions at an early time point and may have a role in the assessment of longitudinal fracture healing. PET scans using ¹⁸F-FDG were not helpful in differentiating metabolic activity between successful and delayed bone healing.     

Combined 18F-FDG and 11C-methionine PET scans in patients with newly progressive metastatic prostate cancer.

Metastatic prostate cancer may respond initially to hormone suppression, with involution of tumor sites, but ultimate tumor progression is inevitable. Our aim was to detect the proportion of bone and soft-tissue lesions that represent metabolically active tumor sites in patients with progressive metastatic prostate cancer. METHODS: In a prospective study, we compared 18F-FDG and L-methyl-11C-methionine (11C-methionine) PET with conventional imaging modalities (CIM), which included the combination of 99mTc-methylene diphosphonate scintigraphy, CT, or MRI. Twelve patients with prostate cancer, increasing levels of prostate-specific antigen (PSA), and at least 1 site (index lesion) with new or increasing disease on CIM were studied. The total numbers of soft-tissue and bone-tissue lesions, in a site-by-site comparison, were calculated for all imaging modalities. RESULTS: The sensitivities of 18F-FDG PET and 11C-methionine PET were 48% (167/348 lesions) and 72.1% (251/348 lesions), respectively, with CIM being used as the 100% reference (348/348). 11C-Methionine PET identified significantly more lesions than 18F-FDG PET (P < 0.01). All 12 patients with progressive metastatic prostate cancer had at least 1 lesion site of active metabolism for 18F-FDG or 11C-methionine, which could be used as an index lesion to monitor the metabolic response to therapy. A significant proportion of lesions (26%) had no detectable metabolism of 18F-FDG or 11C-methionine. Although technical factors cannot be totally excluded, we believe that metabolically inactive sites may be necrotic or dormant. More than 95% (251/258) of metabolically active sites (72% of the total number of lesions detected by CIM) metabolize 11C-methionine. 18F-FDG uptake is more variable, with 65% of metabolically active sites (48% of the total number of lesions detected by CIM). CONCLUSION: These findings reflect the different biologic characteristics of the lesions in a heterogeneous tumor such as prostate cancer and suggest that a time-dependent metabolic cascade may occur in advanced prostate cancer, with initial uptake of 11C-methionine in dormant sites followed by increased uptake of 18F-FDG during progression of disease.     

18F-Fluoride positron emission tomography and positron emission tomography/computed tomography

(18)F-Fluoride is a positron-emitting bone-seeking agent, the uptake of which reflects blood flow and remodeling of bone. Assessment of (18)F-fluoride kinetics using quantitative positron emission tomography (PET) methods allows the regional characterization of lesions of metabolic bone diseases and the monitoring of their response to therapy. It also enables the assessment of bone viability and discrimination of uneventful and impaired healing processes of fractures, bone grafts and osteonecrosis. Taking advantage of the favorable pharmacokinetic properties of the tracer combined with the high performance of PET technology, static (18)F-fluoride PET is a highly sensitive imaging modality for detection of benign and malignant osseous abnormalities. Although (18)F-fluoride uptake mechanism corresponds to osteoblastic activity, it is also sensitive for detection of lytic and early marrow-based metastases, by identifying their accompanying reactive osteoblastic changes, even when minimal. The instant fusion of increased (18)F-fluoride uptake with morphological data of computed tomography (CT) using hybrid PET/CT systems improves the specificity of (18)F-fluoride PET in cancer patients by accurately differentiating between benign and malignant sites of uptake. The results of a few recent publications suggest that (18)F-fluoride PET/CT is a valuable modality in the diagnosis of pathological osseous conditions in patients also referred for nononcologic indications. (18)F-fluoride PET and PET/CT are, however, not widely used in clinical practice. The limited availability of (18)F-fluoride and of PET and PET/CT systems is a major factor. At present, there are not enough data on the cost-effectiveness of (18)F-fluoride PET/CT. However, it has been stated by some experts that (18)F-fluoride PET/CT is expected to replace (99m)Tc-MDP bone scintigraphy in the future.     

骨转移瘤18F—FDGPET／CT影像学表现分析

目的分析骨转移瘤的18F-脱氧葡萄糖（FDG）PET／CT影像学表现。方法140例18F—FDGPET／CT检查病例,按病灶的4种CT形态（成骨改变、溶骨改变、混合改变及无改变）分组,探讨肿瘤骨转移灶代谢表现与形态表现之间的关系,进一步治疗情况与转移灶代谢表现的关系。采用SPSS10．0软件,行Mann—Whitney检验及x2检验。结果140例患者分未治疗组78例（55．7％）,治疗（化疗及内分泌）组62例（44．3％）。共检出病灶1658个,CT示成骨病灶415个（25．0％）,溶骨病灶567个（34．2％）,混合病灶177个（10．7％）,无改变病灶499个（30．1％）。对未治疗组1045个病灶平均标准摄取值（SUVmax。）行Mann—Whitney检验,混合病灶、溶骨病灶SUVmax高于成骨病灶、无改变病灶（SUVmax。中位值分别为5．7,5．2,4．8及4．6,Z=-4．680,-6．067,-2．237,-4．635,P均〈0．05）;治疗组与未治疗组行,检验,未治疗组以溶骨性改变（39．6％）为多,治疗组以成骨性改变（35．9％）为多,组间病灶组成明显不同（x2=67．8,P〈0．05）,治疗组代谢水平明显低于未治疗组（SUVmax中位值分别为4．9及4．6,Z=-4．315,P〈0．05）。结论骨转移病灶形态表现不同,其代谢表现差异明显,溶骨病灶的SUVmax。明显大于无溶骨病灶;化疗及内分泌治疗能通过对病灶转归的改变影响病灶形态及相应代谢表现。     

Malignant involvement of the spine: assessment by 18F-FDG PET/CT.

The purpose of the study was to assess the role of (18)F-FDG PET/CT in the assessment of secondary malignant involvement of the spinal column. METHODS: In 51 patients, 242 lesions at the spinal region detected on (18)F-FDG PET/CT were interpreted separately on PET, CT, and fused PET/CT images, including differentiation between benign and malignant lesions and the level in the vertebral column. CT evaluation also included the type of bony lesion (osteolytic, osteoblastic, or mixed) and accompanying soft-tissue abnormalities; for example, epidural masses and tumor involvement of the neural foramina. RESULTS: Of the 242 lesions detected on PET/CT, PET alone identified 220 lesions and CT alone identified 159; 217 (90%) were malignant and 25 benign. (18)F-FDG PET alone detected significantly more malignant lesions than did CT alone (96% vs. 68%, respectively, P < 0.001). The specificity was 56% for both PET alone and CT alone. PET alone was incorrect in determining the level of abnormality within the vertebral column in 33 (15%) lesions and in determining the part of the vertebra involved in 40 (18%) lesions. In 17 (33%) patients, either epidural extension of tumor (n = 7 lesions), neural foramen involvement of tumor (n = 7 lesions), or a combination of both (n = 11 lesions) was detected. On a patient-based analysis, the sensitivity of PET and of PET/CT for the detection of spinal metastasis was 98% and 74%, respectively (P < 0.01). CONCLUSION: (18)F-FDG PET/CT has better specificity for detection of malignant involvement of the spine than does (18)F-FDG PET. It allows for precise localization of lesions and identifies accompanying soft-tissue involvement, which is of potential neurologic significance.     

The role of 18F-fluoride PET-CT in the detection of bone metastases in patients with breast, lung and prostate carcinoma: a comparison with FDG PET/CT and 99mTc-MDP bone scan

Objectives

We aimed to compare the role of ¹⁸F-fluoride PET/CT, FDG PET/CT and ^99mTc-MDP bone scans in the detection of bone metastases in patients with lung, breast and prostate carcinoma.

Methods

This was a prospective study including patients for staging (S) and restaging (R). Seventy-two patients (23S, 49R) with infiltrating ductal breast carcinoma, 49 patients (25S, 24R) with prostate adenocarcinoma and 30 patients (17S, 13R) with non-small-cell lung carcinoma (NSCLC), without known bone metastases but with high risk/clinical suspicion for the same, underwent a ^99mTc-MDP bone scan, FDG PET/CT and ¹⁸F-fluoride PET/CT within 2 weeks. All scans were reviewed by two experienced nuclear medicine physicians, and the findings were correlated with MRI/thin-slice CT/skeletal survey. Histological verification was done wherever feasible.

Results

Sensitivity and negative predictive value (NPV) of ¹⁸F-fluoride PET/CT was 100 % in all three malignancies, while that of FDG PET/CT was 79 % and 73 % in NSCLC, 73 % and 80 % in breast cancer and 72 and 65 % in prostate cancer. Specificity and positive predictive value (PPV) of FDG PET/CT were 100 % in NSCLC and prostate and 97 % and 96 % in breast cancer. As compared to the ^99mTc-MDP bone scan, all parameters were superior for ¹⁸F-fluoride PET/CT in prostate and breast cancer, but sensitivity and NPV were equal in NSCLC. The MDP bone scan had superior sensitivity and NPV compared to FDG PET/CT but had low specificity and PPV.

Conclusion

To rule out bone metastases in cases where there is a high index of suspicion, ¹⁸F-fluoride PET/CT is the most reliable investigation. ¹⁸F-fluoride PET/CT has the potential to replace the ^99mTc-MDP bone scan for the detection of bone metastases.     

Reproducibility of 18F-FDG microPET studies in mouse tumor xenografts.

(18)F-FDG has been used to image mouse xenograft models with small-animal PET for therapy response. However, the reproducibility of serial scans has not been determined. The purpose of this study was to determine the reproducibility of (18)F-FDG small-animal PET studies. METHODS: Mouse tumor xenografts were formed with B16F10 murine melanoma cells. A 7-min small-animal PET scan was performed 1 h after a 3.7- to 7.4-MBq (18)F-FDG injection via the tail vein. A second small-animal PET scan was performed 6 h later after reinjection of (18)F-FDG. Twenty-five sets of studies were performed. Mean injected dose per gram (%ID/g) values were calculated from tumor regions of interest. The coefficient of variation (COV) from studies performed on the same day was calculated to determine the reproducibility. Activity from the second scans performed after 6 h were adjusted by subtracting the estimated residual activity from the first (18)F-FDG injection. For 7 datasets, an additional scan immediately before the second injection was performed, and residual activity from this additional delayed scan was subtracted from the activity of the second injection. COVs of both subtraction methods were compared. Blood glucose values were measured at the time of injection and used to correct the %ID/g values. RESULTS: The COV for the mean %ID/g between (18)F-FDG small-animal PET scans performed on the same day 6 h apart was 15.4% +/- 12.6%. The delayed scan subtraction method did not produce any significant change in the COV. Blood glucose correction increased the COV. The injected dose, tumor size, and body weight did not appear to contribute to the variability of the scans. CONCLUSION: (18)F-FDG small-animal PET mouse xenograft studies were reproducible with moderately low variability. Therefore, serial small-animal PET studies may be performed with reasonable accuracy to measure tumor response to therapy.     

Assessment of malignant skeletal disease: initial experience with 18F-fluoride PET/CT and comparison between 18F-fluoride PET and 18F-fluoride PET/CT.

18F-fluoride PET/CT was performed on 44 oncologic patients to evaluate its diagnostic accuracy in assessing malignant osseous involvement and in differentiating malignant from benign bone lesions. METHODS: (18)F-fluoride PET and (18)F-fluoride PET/CT were interpreted separately. Lesions showing increased (18)F-fluoride uptake were categorized as malignant, benign, or inconclusive. The final diagnosis of lesions was based on histopathology, correlation with contemporaneous diagnostic CT or MRI, or clinical follow-up of at least 6 mo (mean, 10 +/- 3 mo). RESULTS: Increased (18)F-fluoride uptake was detected at 212 sites, including 111 malignant lesions, 89 benign lesions, and 12 lesions for which the final diagnosis could not be determined. In a lesion-based analysis, the sensitivity of PET alone in differentiating benign from malignant bone lesions was 72% when inconclusive lesions were considered false negative and 90% when inconclusive lesions were considered true positive. On PET/CT, 94 of 111 (85%) metastases presented as sites of increased uptake with corresponding lytic or sclerotic changes, and 16 of the 17 remaining metastases showed normal-appearing bone on CT, for an overall sensitivity of 99% for tumor detection. For only 1 metastasis was PET/CT misleading, suggesting the false diagnosis of a benign lesion. The specificity of PET/CT was significantly higher than that of PET alone (97% vs. 72%, P < 0.001). PET/CT identified benign abnormalities at the location exactly corresponding to the scintigraphic increased uptake for 85 of 89 (96%) benign lesions. In a patient-based analysis, the sensitivity of PET and PET/CT was 88% and 100%, respectively (P < 0.05) and the specificity was 56% and 88%, respectively (not statistically significant). Among the 12 patients referred for (18)F-fluoride assessment because of bone pain despite negative findings on (99m)Tc-methylene diphosphonate bone scintigraphy, (18)F-fluoride PET/CT suggested malignant bone involvement in all 4 patients with proven skeletal metastases, a potential benign cause in 4 of 7 patients who had no evidence of metastatic disease, and a soft-tissue tumor mass invading a sacral foramen in 1 patient. CONCLUSION: The results indicate that (18)F-fluoride PET/CT is both sensitive and specific for the detection of lytic and sclerotic malignant lesions. It accurately differentiated malignant from benign bone lesions and possibly assisted in identifying a potential cause for bone pain in oncologic patients. For most lesions, the anatomic data provided by the low-dose CT of the PET/CT study obviates the performance of full-dose diagnostic CT for correlation purposes.     

Sensitivity in detecting osseous lesions depends on anatomic localization: planar bone scintigraphy versus 18F PET.

Radionuclide bone scanning (RNB) is considered to be the most practical screening technique for assessing the entire skeleton for skeletal metastases. However, RNB has been shown to be of lower sensitivity than MRI and CT in detecting osteolytic metastases. A prospective study was designed to evaluate the accuracy of planar RNB versus tomographic bone imaging with 18F-labeled NaF and PET (18F PET) in detecting osteolytic and osteoblastic metastases and its dependency on their anatomic localization. METHODS: Forty-four patients with known prostate, lung or thyroid carcinoma were examined with both planar RNB and 18F PET. A panel of reference methods including MRI of the spine, 1311 scintigraphy, conventional radiography and spiral CT was used as the gold standard. RNB and 18F PET were compared by a lesion-by-lesion analysis using a five-point score for receiver operating characteristic (ROC) curve analysis. RESULTS: 18F PET showed 96 metastases (67 of prostate carcinoma and 29 of lung or thyroid cancer), whereas RNB revealed 46 metastases (33 of prostate carcinoma and 13 of lung or thyroid cancer). All lesions found with RNB were also detected with 18F PET. Compared with 18F PET and the reference methods, RNB had a sensitivity of 82.8% in detecting malignant and benign osseous lesions in the skull, thorax and extremities and a sensitivity of 40% in the spine and pelvis. The area under the ROC curve was 0.99 for 18F PET and 0.64 for RNB. CONCLUSION: 18F PET is more sensitive than RNB in detecting osseous lesions. With RNB, sensitivity in detecting osseous metastases is highly dependent on anatomic localization of these lesions, whereas detection rates of osteoblastic and osteolytic metastases are similar. Higher detection rates and more accurate differentiation between benign and malignant lesions with 18F PET suggest the use of 18F PET when possible.     

18F-氟乙基胆碱对前列腺癌PET/CT诊断的价值及其非前列腺癌相关摄取的研究

目的 探讨18F-氟乙基胆碱(FECH) PET/CT在前列腺癌诊断中的价值,并分析前列腺癌患者的18F-FECH生理性摄取和其他非前列腺癌相关的摄取.方法 回顾性分析2009年10月至2011年12月共30例行18F-FECH和18F-FDG PET/CT的前列腺癌患者[年龄56～83(平均61)岁],比较两者对前列腺癌原发灶诊断的灵敏度及准确性.测量并分析器官18F-FECH生理性摄取及非前列腺癌病灶摄取的SUVmax.对数据行x2检验和t检验.结果 30例患者中PET/CT共发现41个前列腺异常摄取灶.18F-FECH和18F-FDG显像对前列腺癌原发灶诊断灵敏度分别为87.9％(29/33)和36.4％(12/33;x2=8.1,P＜0.05),准确性分别为82.9％(34/41)和36.6％(15/41;x2=11.1,P＜0.05).肝脏、胰腺、脾脏、唾液腺可见18F-FECH生理性摄取,其中肝脏、胰腺生理性摄取最高,SUVmax分别为10.1±1.6和6.1±1.1.18F-FECH主要经肾脏排泄,泌尿系统可见放射性分布.18F-FECH PET/CT显像前列腺癌与前列腺良性病灶的SUVmax分别为6.0±2.2和2.6±1.3,差异有统计学意义(t=2.9,P＜0.05).30例患者中,发现10例有前列腺以外组织器官的非前列腺癌相关的PET异常表现,占33.3％,其中6例为炎性反应,1例为淋巴瘤,1例为结核,1例为肺癌,1例为松果体生殖细胞瘤.结论 18F-FECH显像在前列腺癌的诊断中有较高价值.准确分析患者生理性摄取及非前列腺癌相关病灶的摄取对前列腺癌的诊断至关重要,造成18F-FECH假阳性的良性病变主要是炎性反应.     

Noninvasive assessment of Crohn's disease intestinal lesions with (18)F-FDG PET/CT.

Pilot studies have shown good sensitivity and specificity for (18)F-FDG PET in detecting gastrointestinal lesions of Crohn's disease. The combination of (18)F-FDG PET with CT may further improve the localization and characterization of lesions with increased (18)F-FDG uptake. Our aim was to assess the use of (18)F-FDG PET/CT in evaluating the activity and location of Crohn's disease along the gastrointestinal tract. METHODS: After giving informed consent, 22 patients with Crohn's disease were prospectively studied. They underwent (18)F-FDG PET/CT, followed by ileocolonoscopy within 1 wk (mean, 2 d). The Crohn's disease activity index (CDAI) was calculated, and serum C-reactive protein (CRP) and fecal calprotectin were measured before endoscopy. The Crohn's disease endoscopy index of severity (CDEIS) was calculated during endoscopy. The global CDEIS score and endoscopic subscores for various ileocolonic segments were used for analysis. RESULTS: Globally, 95 intestinal and colonic segments in 22 patients were analyzed. (18)F-FDG PET/CT detected 35 of 48 endoscopically affected segments (sensitivity for the detection of endoscopic lesions, 72.9%). The sensitivity of (18)F-FDG PET/CT for the detection of severe endoscopic lesions (deep ulcers and strictures) was 100% (14/14). The global PET/CT score significantly correlated with CDEIS (r = 0.51; 95% confidence interval [CI], 0.09-0.77; P = 0.017), CDAI (r = 0.58; 95% CI, 0.17-0.80; P = 0.005), and CRP (r = 0.56; 95% CI, 0.19-0.81; P = 0.007). CONCLUSION: (18)F-FDG PET/CT was globally well correlated to the clinical, endoscopic, and biologic activity of Crohn's disease. Above all, this technique had a good sensitivity for the detection of intestinal and colonic segments with moderate to severe mucosal lesions. The potential impact of this promising tool on the global management of patients with Crohn's disease should be further evaluated in prospective studies.     

18F-FDG PET/CT delayed images after diuretic for restaging invasive bladder cancer.

PET with (18)F-FDG has been considered of limited value for detection of bladder cancer because of the urinary excretion of the tracer. The purpose of this study was to investigate the role of PET/CT in the detection and restaging of bladder cancer using furosemide and oral hydration to remove the excreted (18)F-FDG from the bladder. METHODS: Seventeen patients with bladder cancer (11 without cystectomy, 6 with total cystectomy and urinary diversion) underwent (18)F-FDG PET/CT from head to the upper thighs 60 min after the intravenous injection of 370 MBq of (18)F-FDG. Additional pelvic images were acquired 1 h after the intravenous injection of furosemide and oral hydration. PET/CT findings were confirmed by MRI, cystoscopy, or biopsy. RESULTS: PET/CT was able to detect bladder lesions in 6 of 11 patients who had not undergone cystectomy. These images changed the PET/CT final reading in 7 patients: Recurrent bladder lesions were detected in 6 patients, pelvic lymph node metastases in 2 patients, and prostate metastasis in 1. This technique overcame the difficulties posed by the urinary excretion of (18)F-FDG. Hypermetabolic lesions could be easily detected by PET and precisely localized in the bladder wall, pelvic lymph nodes, or prostate by CT. Seven of 17 patients (41%) were upstaged only after delayed pelvic images. CONCLUSION: Detection of locally recurrent or residual bladder tumors can be dramatically improved using (18)F-FDG PET/CT with delayed images after a diuretic and oral hydration.     

Improvement of semi-quantitative small-animal PET data with recovery coefficients: a phantom and rat study

AIM: To evaluate the accuracy of semi-quantitative small-animal PET data, uncorrected for attenuation, and then of the same semi-quantitative data corrected by means of recovery coefficients (RCs) based on phantom studies. MATERIALS AND METHODS: A phantom containing six fillable spheres (diameter range: 4.4-14 mm) was filled with an 18F-FDG solution (spheres/background activity=10.1, 5.1 and 2.5). RCs, defined as measured activity/expected activity, were calculated. Nude rats harbouring tumours (n=50) were imaged after injection of 18F-FDG and sacrificed. The standardized uptake value (SUV) in tumours was determined with small-animal PET and compared to ex-vivo counting (ex-vivo SUV). Small-animal PET SUVs were corrected with RCs based on the greatest tumour diameter. Tumour proliferation was assessed with cyclin A immunostaining and correlated to the SUV. RESULTS: RCs ranged from 0.33 for the smallest sphere to 0.72 for the largest. A sigmoidal correlation was found between RCs and sphere diameters (r(2)=0.99). Small-animal PET SUVs were well correlated with ex-vivo SUVs (y=0.48x-0.2; r(2)=0.71) and the use of RCs based on the greatest tumour diameter significantly improved regression (y=0.84x-0.81; r(2)=0.77), except for tumours with important necrosis. Similar results were obtained without sacrificing animals, by using PET images to estimate tumour dimensions. RC-based corrections improved correlation between small-animal PET SUVs and tumour proliferation (uncorrected data: Rho=0.79; corrected data: Rho=0.83). CONCLUSION: Recovery correction significantly improves both accuracy of small-animal PET semi-quantitative data in rat studies and their correlation with tumour proliferation, except for largely necrotic tumours.     

Comparison of 18F-FLT PET and 18F-FDG PET in esophageal cancer.

18F-FDG PET has gained acceptance for staging of esophageal cancer. However, FDG is not tumor specific and false-positive results may occur by accumulation of FDG in benign tissue. The tracer 18F-fluoro-3'-deoxy-3'-L-fluorothymidine (18F-FLT) might not have these drawbacks. The aim of this study was to investigate the feasibility of 18F-FLT PET for the detection and staging of esophageal cancer and to compare 18F-FLT PET with 18F-FDG PET. Furthermore, the correlation between 18F-FLT and 18F-FDG uptake and proliferation of the tumor was investigated. METHODS: Ten patients with biopsy-proven cancer of the esophagus or gastroesophageal junction were staged with CT, endoscopic ultrasonography, and ultrasound of the neck. In addition, all patients underwent a whole-body 18F-FLT PET and 18F-FDG PET. Standardized uptake values were compared with proliferation expressed by Ki-67 positivity. RESULTS: 18F-FDG PET was able to detect all esophageal cancers, whereas 18F-FLT PET visualized the tumor in 8 of 10 patients. Both 18F-FDG PET and 18F-FLT PET detected lymph node metastases in 2 of 8 patients. 18F-FDG PET detected 1 cervical lymph node that was missed on 18F-FLT PET, whereas 18F-FDG PET showed uptake in benign lesions in 2 patients. The uptake of 18F-FDG (median standardized uptake value [SUV(mean)], 6.0) was significantly higher than 18F-FLT (median SUV(mean), 3.4). Neither 18F-FDG maximum SUV (SUV(max)) nor 18F-FLT SUV(max) correlated with Ki-67 expression in the linear regression analysis. CONCLUSION: In this study, uptake of 18F-FDG in esophageal cancer is significantly higher compared with 18F-FLT uptake. 18F-FLT scans show more false-negative findings and fewer false-positive findings than do 18F-FDG scans. Uptake of 18F-FDG or 18F-FLT did not correlate with proliferation.     

Positron emission tomography with 11C-acetate and 18F-FDG in prostate cancer patients

Visualisation of primary prostate cancer, its relapse and its metastases is a clinically relevant problem despite the availability of state-of-the-art methods such as CT, MRI, transrectal ultrasound and fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET). The aim of this study was to evaluate the efficacy of carbon-11 acetate and (18)F-FDG PET in the detection of prostate cancer and its metastases. Twenty-five patients were investigated during the follow-up of primary prostate cancer, suspected relapse or metastatic disease using (11)C-acetate PET; 15 of these patients were additionally investigated using (18)F-FDG PET. Fourteen patients were receiving anti-androgen treatment at the time of the investigation. Lesions were detected in 20/24 (83%) patients using (11)C-acetate PET and in 10/15 (75%) patients using (18)F-FDG PET. Based on the results of both PET scans, one patient was diagnosed with recurrent lung cancer. Median (18)F-FDG uptake exceeded that of (11)C-acetate in distant metastases (SUV =3.2 vs 2.3). However, in local recurrence and in regional lymph node metastases, (11)C-acetate uptake (median SUVs =2.9 and 3.8, respectively) was higher than that of (18)F-FDG (median SUVs =1.0 and 1.1, respectively). A positive correlation was observed between serum PSA level and both (11)C-acetate uptake and (18)F-FDG uptake. (11)C-acetate seems more useful than (18)F-FDG in the detection of local recurrences and regional lymph node metastases. (18)F-FDG, however, appears to be more accurate in visualising distant metastases. There may be a role for combined (11)C-acetate/(18)F-FDG PET in the follow-up of patients with prostate cancer and persisting or increasing PSA.     

Significance of incidental 18F-FDG accumulations in the gastrointestinal tract in PET/CT: correlation with endoscopic and histopathologic results.

This study was undertaken to identify the clinical value of incidentally detected lesions (IDLs) in the gastrointestinal tract (GIT) with (18)F-FDG PET/CT. METHODS: The reported database of 3,281 patients who underwent partial-body (18)F-FDG PET/CT scans from April 2001 to September 2003 was reviewed. Patients with incidental (18)F-FDG accumulations in the GIT that were associated with concomitant abnormal soft-tissue density or wall thickening on the native CT were evaluated. Incidental PET/CT findings were correlated with endoscopic and histopathologic results. RESULTS: According to our selection criteria, 98 (3%) of the 3,281 patients had an IDL of the GIT on (18)F-FDG PET/CT. Correlative endoscopic findings were available in 69 (70%) of 98 patients. Of these, 13 patients (19%) were harboring newly occurring cancers of the GIT in addition to preexisting aerodigestive tract tumors (n = 12) and malignant melanoma (n = 1). Twenty-nine (42%) patients were identified with precancerous lesions, such as advanced colonic adenomas (n = 27), Barrett's esophagus (n = 1), and intestinal metaplasia of the gastric mucosa (n = 1). Inflammatory and other benign GIT lesions were detected in 12 (17%) and 6 (8%) patients, respectively. In 9 (13%) patients, PET/CT was false-positive, showing normal findings in subsequent endoscopic examinations. In 20 (28%) of 69 patients, PET/CT findings had a relevant impact on the clinical management. Twenty-nine (30%) of the 98 patients were not subject to a further endoscopic examination because of the extent and nature of the primary tumor (n = 17), loss to follow-up (n = 7), death shortly after PET (n = 3), and patient unwillingness (n = 2). CONCLUSION: Although IDLs of the GIT on (18)F-FDG PET/CT scans are found only in about 3% of cases, they are associated with a substantial risk of an underlying cancerous or precancerous lesion. Early identification of these occult lesions may have a major impact on the patients' management and outcome.     

Comparisons between glucose analogue 2-deoxy-2-(18F)fluoro-D-glucose and 18F-sodium fluoride positron emission tomography/computed tomography in breast cancer patients with bone lesions

AIM: To compare 2-deoxy-2-(¹⁸F)fluoro-D-glucose(¹⁸F-FDG) and ¹⁸F-sodium (¹⁸F-NaF) positron emission tomography/computed tomography (PET/CT) accuracy in breast cancer patients with clinically/radiologically suspected or known bone metastases.METHODS: A total of 45 consecutive patients with breast cancer and the presence or clinical/biochemical or radiological suspicion of bone metastatic disease underwent ¹⁸F-FDG and ¹⁸F-fluoride PET/CT. Imaging results were compared with histopathology when available, or clinical and radiological follow-up of at least 1 year. For each technique we calculated: Sensitivity (Se), specificity (Sp), overall accuracy, positive and negative predictive values, error rate, and Youden’s index. McNemar’s χ² test was used to test the difference in sensitivity and specificity between the two diagnostic methods. All analyses were computed on a patient basis, and then on a lesion basis, with consideration ofthe density of independent lesions on the co-registered CT (sclerotic, lytic, mixed, no-lesions) and the divergent site of disease (skull, spine, ribs, extremities, pelvis). The impact of adding ¹⁸F-NaF PET/CT to the work-up of patients was also measured in terms of change in their management due to ¹⁸F-NaF PET/CT findings.RESULTS: The two imaging methods of ¹⁸F-FDG and ¹⁸F-fluoride PET/CT were significantly different at the patient-based analysis: Accuracy was 86.7% and 84.4%, respectively (McNemar’s χ² = 6.23, df = 1, P = 0.01). Overall, 244 bone lesions were detected in our analysis. The overall accuracy of the two methods was significantly different at lesion-based analysis (McNemar’s χ² = 93.4, df = 1, P < 0.0001). In the lesion density-based and site-based analysis, ¹⁸F-FDG PET/CT provided more accurate results in the detection of CT-negative metastasis (P < 0.002) and vertebral localizations (P < 0.002); ¹⁸F-NaF PET/CT was more accurate in detecting sclerotic (P < 0.005) and rib lesions (P < 0.04). ¹⁸F-NaF PET/CT led to a change of management in 3 of the 45 patients (6.6%) by revealing findings that were not detected at ¹⁸F-FDG PET/CT.CONCLUSION: ¹⁸F-FDG PET/CT is a reliable imaging tool in the detection of bone metastasis in most cases, with a diagnostic accuracy that is slightly, but significantly, superior to that of ¹⁸F-NaF PET/CT in the general population of breast cancer patients. However, the extremely high sensitivity of ¹⁸F-fluoride PET/CT can exploit its diagnostic potential in specific clinical settings (i.e., small CT-evident sclerotic lesions, high clinical suspicious of relapse, and negative ¹⁸F-FDG PET and conventional imaging).     

The role of 18F-FDG PET in staging and early prediction of response to therapy of recurrent gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are gaining the interest of researchers because of impressive metabolic response to the targeted molecular therapeutic drug imatinib mesylate. Initial reports suggest an impressive role for (18)F-FDG PET in follow-up of therapy for these tumors. However, the role of (18)F-FDG PET versus that of CT has not been established. Therefore, we compared the roles of (18)F-FDG PET and CT in staging and evaluation of early response to imatinib mesylate therapy in recurrent or metastatic GIST. METHODS: The study included 54 patients who underwent (18)F-FDG PET and CT scans within 3 wk before initiation of imatinib mesylate therapy. Forty-nine of these patients underwent repeat scans 2 mo after therapy. The numbers of sites or organs containing lesions on (18)F-FDG PET and CT scans were compared. Corresponding lesions on (18)F-FDG PET and CT scans or those confirmed to be malignant in appearance by other imaging modalities or on follow-up were considered true positives. Lesions seen on (18)F-FDG PET or CT scans but not seen or confirmed to be of benign appearance with other imaging modalities or on follow-up were considered false positives. Measurements of the maximum standard uptake value (SUV) on (18)F-FDG PET scans and tumor size on CT scans were used for quantitative evaluation of early tumor response to therapy. RESULTS: A total of 122 and 114 sites and/or organs were involved on pretherapy (18)F-FDG PET and CT scans, respectively. The sensitivity and positive predictive values (PPVs) for CT were 93% and 100%; whereas these values for (18)F-FDG PET were 86% and 98%. However, the differences between these values for CT and (18)F-FDG PET were not statistically significant (P = 0.27 for sensitivity and 0.25 for PPV). This suggests comparable performance of (18)F-FDG PET and CT in staging GISTs. Repeat scans at 2 mo after therapy showed agreement between (18)F-FDG PET and CT scans in 71.4% of patients (57.1% having a good response to therapy and 14.3% lacking a response). Discrepant results between (18)F-FDG PET and CT were recorded for 28.6% of the patients. (18)F-FDG PET predicted response to therapy earlier than did CT in 22.5% of patients during a longer follow-up interval (4-16 mo), whereas CT predicted lack of response to therapy earlier than (18)F-FDG PET in 4.1%. One patient did not undergo long-term follow-up. These findings suggest that (18)F-FDG PET is superior to CT in predicting early response to therapy in recurrent or metastatic GIST patients. CONCLUSION: The performances of (18)F-FDG PET and CT are comparable in staging GISTs before initiation of imatinib mesylate therapy. However, (18)F-FDG PET is superior to CT in predicting early response to therapy. Thus, (18)F-FDG PET is a better guide for imatinib mesylate therapy.     

18F-FDG PET in evaluation of adrenal lesions in patients with lung cancer.

The purpose of this study was to assess the role of PET with (18)F-FDG in differentiating benign from metastatic adrenal masses detected on CT or MRI scans of patients with lung cancer. METHODS: This retrospective study analyzed (18)F-FDG PET scans of patients with lung cancer who were found to have an adrenal mass on CT or MRI scans. One hundred thirteen adrenal masses (75 unilateral and 19 bilateral; size range, 0.8-4.7 cm) were evaluated in 94 patients. PET findings were interpreted as positive if the (18)F-FDG uptake of the adrenal mass was greater than or equal to that of the liver. PET findings were interpreted as negative if the (18)F-FDG uptake of the adrenal mass was less than that of the liver. All studies were reviewed independently by 3 nuclear medicine physicians, and the results were then correlated with clinical follow-up or biopsy results when available. RESULTS: PET findings were positive in 71 adrenal masses. Sixty-seven of these were eventually considered to be metastatic adrenal disease. In the remaining 4, no changes in lesion size were noted on follow-up examinations. PET findings were negative in 42 adrenal masses, of which 37 eventually proved to be benign. Among the 5 adrenal masses that were false-negative, one was a large necrotic metastasis; 1 was a 2.4-cm lesion with central hemorrhaging, and the remaining 3 were lesions of less than 11 mm. The sensitivity, specificity, and accuracy for detecting metastatic disease were 93%, 90%, and 92%, respectively. CONCLUSION: (18)F-FDG PET is an accurate, noninvasive technique for differentiating benign from metastatic adrenal lesions detected on CT or MRI in patients with lung cancer. In addition, PET has the advantage of assessing the primary cancer sites and detecting other metastases.