Novel synthesis and preclinical evaluation of folic acid derivatives labeled with (18)F-[FDG] for PET imaging of folate receptor-positive tumors

There is a need to develop more potent radiofluorinated folic acid conjugates for a better visualization of folate receptors that overexpress on many human cancers. Due to the clinical importance of [¹⁸F]-fluoro-2-deoxy-d-glucose ([¹⁸F]-FDG) and its availability in almost every positron-emission tomography center, new radiofluorinated [¹⁸F]-FDG-folate and methotrexate conjugates ([¹⁸F]-5 and [¹⁸F]-8) were synthesized using [¹⁸F]-FDG as a prosthetic group. In a convenient and simple one-step radiosynthesis, [¹⁸F]-5 and [¹⁸F]-8 conjugates were prepared in high radiochemical yields (> 80%) with total synthesis time of almost 20 min, and radiochemical purities were found to be greater than 98% without high-performance liquid chromatography purification, which make these approaches amenable for automation. In vitro tests on KB cell line showed that a significant amount of the radioconjugates were associated with the cell fractions. In vivo characterization in normal Balb/c mice revealed rapid blood clearance of these radioconjugates with excretion predominantly by the urinary and hepatobiliary systems for [¹⁸F]-5 and [¹⁸F]-8 conjugates, respectively. Biodistribution studies in nude mice-bearing human KB cell line xenografts demonstrated significant tumor uptake and favorable kinetics profile for [¹⁸F]-5 over the other conjugate. The uptake in the tumors was blocked by the excess coinjection of cold folic acid, suggesting the receptor-mediated process. These results demonstrate that [¹⁸F]-5 may be useful as a molecular probe for detecting and staging of folate receptor-positive cancers, such as ovarian cancer and their metastasis, as well as monitoring tumor response to the treatment.     

Synthesis and preclinical evaluation of a folic acid derivative labeled with 18F for PET imaging of folate receptor-positive tumors.

Folic acid was linked regioselectively through its alpha- and gamma-carboxyl groups to 4-fluorobenzylamine (FBA), and the alpha- and gamma-FBA-folate regioisomers were evaluated for their ability to bind to folate receptor-positive cells. The 18F-labeled alpha/gamma-FBA-folate counterpart was examined for in vivo tumor targeting efficiency in nude mice bearing folate receptor-positive tumor cells. METHODS: 18F-alpha/gamma-FBA-folate was prepared in a 4-step reaction sequence starting from folic acid. The relative binding affinities of the alpha- and gamma-FBA-folates to the folate receptor with respect to parent folic acid were determined in cultured KB-31 cells (nasopharyngeal epidermal carcinoma cell line) overexpressing the folate receptor using 3H-folic acid. Tumor accumulation of the 18F-labeled alpha/gamma-FBA-folate and 18F-FDG was analyzed in vivo by high-resolution PET. Biodistribution and PET studies were performed under baseline and blockage conditions. RESULTS: The radiochemical yield of the coupling step ranged from 15% to 44%, and the maximum specific radioactivity was 24 GBq/micromol. The in vitro binding affinities of the alpha- and gamma-isomers and folic acid were 71, 62, and 41 nmol/L, respectively. PET revealed heterogeneous uptake of the radioligand, with the highest activity concentrations found in the tumor rim. In contrast, 18F-FDG uptake in a nude mouse bearing KB-31 folate receptor-positive tumors was negligible. Radioligand uptake in tumors at 125 min after injection amounted to 6.56% of the injected dose per gram of tissue (%ID/g) in control animals, whereas radioactivity accumulation in the tumors of folic acid-treated animals was significantly reduced by more than 80%-to 1.07 %ID/g (P = 0.001). CONCLUSION: This new 18F-labeled folic acid derivative is a promising tool for PET imaging of folate receptor-positive tumors.     

Guidelines for 18F-FDG PET and PET-CT imaging in paediatric oncology

OBJECTIVE: The purpose of these guidelines is to offer to the nuclear medicine team a framework that could prove helpful in daily practice. These guidelines contain information related to the indications, acquisition, processing and interpretation of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in paediatric oncology. The Oncology Committee of the European Association of Nuclear Medicine (EANM) has published excellent procedure guidelines on tumour imaging with (18)F-FDG PET (Bombardieri et al., Eur J Nucl Med Mol Imaging 30:BP115-24, 2003). These guidelines, published by the EANM Paediatric Committee, do not intend to compete with the existing guidelines, but rather aim at providing additional information on issues particularly relevant to PET imaging of children with cancer. CONCLUSION: The guidelines summarize the views of the Paediatric Committee of the European Association of Nuclear Medicine. They should be taken in the context of "good practice" of nuclear medicine and of any national rules, which may apply to nuclear medicine examinations. The recommendations of these guidelines cannot be applied to all patients in all practice settings. The guidelines should not be deemed inclusive of all proper procedures or exclusive of other procedures reasonably directed to obtaining the same results.     

Differential diagnosis of patients with atypical Parkinsonian syndrome using 18F-FDG and 18F-FP CIT PET: A report of five cases

We describe 5 cases of patients who presented atypical parkinsonian syndrome (APS), including gait disturbance, postural instability, decreasing facial expression, dyskinesia, and subjective cognitive impairment. The patients underwent ¹⁸F-FP-CIT PET and ¹⁸F-FDG PET consecutively for differential diagnosis of APS. Through PET imaging examination, it was possible to offer a suggestive diagnosis and determine individual strategic management for patients with APS.     

Tumour hypoxia imaging with [18F]FAZA PET in head and neck cancer patients: a pilot study

Purpose Hypoxia is an important negative prognostic factor for radiation treatment of head and neck cancer. This study was performed to evaluate the feasibility of use of ¹⁸F-labelled fluoroazomycin arabinoside ([¹⁸F]FAZA) for clinical PET imaging of tumour hypoxia. Methods Eleven patients (age 59.6 ± 9 years) with untreated advanced head and neck cancer were included. After injection of approximately 300 MBq of [¹⁸F]FAZA, a dynamic sequence up to 60 min was acquired on an ECAT HR+ PET scanner. In addition, approximately 2 and 4 h p.i., static whole-body PET (n = 5) or PET/CT (n = 6) imaging was performed. PET data were reconstructed iteratively (OSEM) and fused with CT images (either an external CT or the CT of integrated PET/CT). Standardised uptake values (SUVs) and tumour-to-muscle (T/M) ratios were calculated in tumour and normal tissues. Also, the tumour volume displaying a T/M ratio >1.5 was determined. Results Within the first 60 min of the dynamic sequence, the T/M ratio generally decreased, while generally increasing at later time points. At 2 h p.i., the tumour SUV_max and SUV_mean were found to be 2.3 ± 0.5 (range 1.5–3.4) and 1.4 ± 0.3 (range 1.0–2.1), respectively. The mean T/M ratio at 2 h p.i. was 2.0 ± 0.3 (range 1.6–2.4). The tumour volume displaying a T/M ratio above 1.5 was highly variable. At 2 h p.i., [¹⁸F]FAZA organ distribution was determined as follows: kidney > gallbladder > liver > tumour > muscle > bone > brain > lung. Conclusion [¹⁸F]FAZA PET imaging appears feasible in head and neck cancer patients, and the achieved image quality is adequate for clinical purposes. Based on our initial results, [¹⁸F]FAZA warrants further evaluation as a hypoxia PET tracer for imaging of cancer.     

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.     

Detection of gastric cancer using <Superscript>18</Superscript>F-FLT PET: comparison with <Superscript>18</Superscript>F-FDG PET

Purpose  We prospectively investigated the feasibility of 3′-deoxy-3′-¹⁸F-fluorothymidine (FLT) positron emission tomography (PET) for the detection of gastric cancer, in comparison with 2-deoxy-2-¹⁸F-fluoro-d-glucose (FDG) PET, and determined the degree of correlation between the two radiotracers and proliferative activity as indicated by Ki-67 index. Methods  A total of 21 patients with newly diagnosed advanced gastric cancer were examined with FLT PET and FDG PET. Tumour lesions were identified as areas of focally increased uptake, exceeding that of surrounding normal tissue. For semiquantitative analysis, the maximal standardized uptake value (SUV) was calculated. Results  For detection of advanced gastric cancer, the sensitivities of FLT PET and FDG PET were 95.2% and 95.0%, respectively. The mean (±SD) SUV for FLT (7.0 ± 3.3) was significantly lower than that for FDG (9.4 ± 6.3 p < 0.05). The mean FLT SUV and FDG SUV in nonintestinal tumours were higher than in intestinal tumours, although the difference was not statistically significant. The mean (±SD) FLT SUV in poorly differentiated tumours (8.5 ± 3.5) was significantly higher than that in well and moderately differentiated tumours (5.3 ± 2.1; p < 0.04). The mean FDG SUV in poorly differentiated tumours was higher than in well and moderately differentiated tumours, although the difference was not statistically significant. There was no significant correlation between Ki-67 index and either FLT SUV or FDG SUV. Conclusion  FLT PET showed as high a sensitivity as FDG PET for the detection of gastric cancer, although uptake of FLT in gastric cancer was significantly lower than that of FDG.     

(18)F-FDG PET versus (18)F-FDG PET/CT for adrenal gland lesion characterization: a comparison of diagnostic efficacy in lung cancer patients.

OBJECTIVE: The aim of this study was to assess the diagnostic efficacy of integrated PET/CT using fluorodeoxyglucose (FDG) for the differentiation of benign and metastatic adrenal gland lesions in patients with lung cancer and to compare the diagnostic efficacy with the use of PET alone. MATERIALS AND METHODS: Sixty-one adrenal lesions (size range, 5-104 mm; mean size, 16 mm) were evaluated retrospectively in 42 lung cancer patients. Both PET images alone and integrated PET/CT images were assessed, respectively, at two-month intervals. PET findings were interpreted as positive if the FDG uptake of adrenal lesions was greater than or equal to that of the liver, and the PET/CT findings were interpreted as positive if an adrenal lesion show attenuation > 10 HU and showed increased FDG uptake. Final diagnoses of adrenal gland lesions were made at clinical follow-up (n = 52) or by a biopsy (n = 9) when available. The diagnostic accuracies of PET and PET/CT for the characterization of adrenal lesions were compared using the McNemar test. RESULTS: Thirty-five (57%) of the 61 adrenal lesions were metastatic and the remaining 26 lesions were benign. For the depiction of adrenal gland metastasis, the sensitivity, specificity, and accuracy of PET were 74%, 73%, and 74%, respectively, whereas those of integrated PET/CT were 80%, 89%, and 84%, respectively (p values; 0.5, 0.125, and 0.031, respectively). CONCLUSION: The use of integrated PET/CT is more accurate than the use of PET alone for differentiating benign and metastatic adrenal gland lesions in lung cancer patients.     

Assessment of lymph node metastases using 18F-FDG PET in patients with advanced gastric cancer

Purpose The aim of this study was to assess the diagnostic accuracy of ¹⁸F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) with respect to lymph node (LN) metastasis in patients with advanced gastric cancer, and to ascertain the factors that affect this accuracy.Methods Seventy-three patients with advanced gastric cancer, verified in all cases by endoscopic biopsy, were enrolled in this prospective study. We conducted FDG PET and other routine preoperative studies, including abdominal computed tomography (CT). Patients underwent either curative-intent gastrectomy and lymphadenectomy (n=67) or exploratory laparotomy. The Japanese system for the classification of gastric cancer was used for LN assessment.Results FDG PET was able to detect primary lesions in 70 of the 73 cases. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value of FDG PET for LN metastasis were 40%, 95%, 91% and 56%, respectively. Signet-ring cell carcinoma was associated with the lowest sensitivity (15%), whereas other cell types could be detected with moderate sensitivity (30–71%) and high specificity (93–100%). According to multiple logistic regression, the standardised uptake value for primary tumours was the only independent variable to be significantly related to sensitivity for LN metastasis (p=0.02, odds ratio=1.14). CT was superior to PET in terms of sensitivity (p<0.0001), and PET was superior to CT in terms of specificity (p<0.0001) and PPV (p=0.05).Conclusion FDG PET exhibits good specificity for LN staging of gastric cancer, and FDG uptake in the primary tumour is significantly related to the accuracy of FDG PET. Despite some clear limitations, FDG PET proved useful in the LN staging of FDG-avid gastric cancer.Seok-Ki Kim and Keon Wook Kang contributed equally to this paper.     

Cutaneous metastatic lung cancer detected with18F-FDG PET

A 48-year-old male smoker presented with a chief complaint of persistent cough for three months. A CT scan revealed only a large right paratracheal mass. The plan was to obtain histological confirmation of suspected lung cancer via bronchoscopy and mediastinoscopy. A whole body 18F-FDG (2-deoxy-2-[18F]fluoro-D-glucose) PET Scan was ordered for staging and localization of the most accessible biopsy site. There was a large, intense hypermetabolic focus corresponding to the paratracheal lesion seen on CT, as well as a lesion in the right adrenal gland. There was also a superficial, subcutaneous hypermetabolic lesion in the mid-back. The subcutaneous lesion, which previously had not been noted, was biopsied and proved to be metastatic adenocarcinoma consistent with the lung primary. This case illustrates the clinical utility of reporting soft tissue abnormalities, which may provide an alternative, more readily accessible location for biopsy that is both safer and less expensive than bronchoscopy or mediastinoscopy.     

Direct comparison of [18F]FDG PET/CT with PET alone and with side-by-side PET and CT in patients with malignant melanoma

Purpose

The purpose of this retrospective, blinded study was to evaluate the additional value of [¹⁸F]FDG PET/CT in comparison with PET alone and with side-by-side PET and CT in patients with malignant melanoma (MM).

Methods

A total of 127 consecutive studies of patients with known MM referred for a whole-body PET/CT examination were included in this study. PET alone, side-by-side PET and CT and integrated PET/CT study were independently and separately interpreted without awareness of the clinical information. One score each was applied for certainty of lesion localisation and for certainty of lesion characterisation. Verification of the findings was subsequently performed using all available clinical, pathological (n?=?30) and follow-up information.

Results

The number of lesions with an uncertain localisation was significantly (p?p?p?=?0.057) compared versus PET alone. Respectively, PET, side-by-side PET and CT and PET/CT showed a sensitivity of 86%, 89% and 91%, a specificity of 94%, 94% and 94%, a positive predictive value of 96%, 96% and 96% and a negative predictive value of 80%, 83% and 87%.

Conclusion

Integrated PET/CT offers a significant benefit in lesion localisation and an improvement in lesion characterisation compared with PET alone or with side-by-side PET and CT. The benefit is not as great as that reported for other tumour entities, which may be due to the high avidity of MM for [¹⁸F]FDG.     

Comparisons of [18F]-1-deoxy-1-fluoro-scyllo-inositol with [18F]-FDG for PET imaging of inflammation, breast and brain cancer xenografts in athymic mice

Introduction

The aim of the study was to evaluate the uptake of [¹⁸F]-1-deoxy-1-fluoro-scyllo-inositol ([¹⁸F]-scyllo-inositol) in human breast cancer (BC) and glioma xenografts, as well as in inflammatory tissue, in immunocompromised mice. Studies of [¹⁸F]-2-fluoro-2-deoxy-d-glucose ([¹⁸F]-FDG) under the same conditions were also performed.

Methods

Radiosynthesis of [¹⁸F]-scyllo-inositol was automated using a commercial synthesis module. Tumour, inflammation and normal tissue uptakes were evaluated by biodistribution studies and positron emission tomography (PET) imaging using [¹⁸F]-scyllo-inositol and [¹⁸F]-FDG in mice bearing subcutaneous MDA-MB-231, MCF-7 and MDA-MB-361 human BC xenografts, intracranial U-87 MG glioma xenografts and turpentine-induced inflammation.

Results

The radiosynthesis of [¹⁸F]-scyllo-inositol was automated with good radiochemical yields (24.6%±3.3%, uncorrected for decay, 65±2 min, n=5) and high specific activities (≥195 GBq/μmol at end of synthesis). Uptake of [¹⁸F]-scyllo-inositol was greatest in MDA-MB-231 BC tumours and was comparable to that of [¹⁸F]-FDG (4.6±0.5 vs. 5.5±2.1 %ID/g, respectively; P=.40), but was marginally lower in MDA-MB-361 and MCF-7 xenografts. Uptake of [¹⁸F]-scyllo-inositol in inflammation was lower than [¹⁸F]-FDG. While uptake of [¹⁸F]-scyllo-inositol in intracranial U-87 MG xenografts was significantly lower than [¹⁸F]-FDG, the tumour-to-brain ratio was significantly higher (10.6±2.5 vs. 2.1±0.6; P=.001).

Conclusions

Consistent with biodistribution studies, uptake of [¹⁸F]-scyllo-inositol was successfully visualized by PET imaging in human BC and glioma xenografts, with lower accumulation in inflammatory tissue than [¹⁸F]-FDG. The tumour-to-brain ratio of [¹⁸F]-scyllo-inositol was also significantly higher than that of [¹⁸F]-FDG for visualizing intracranial glioma xenografts in NOD SCID mice, giving a better contrast.     

18F-FDG PET in the management of endometrial cancer

Purpose Few studies have investigated the clinical impact of whole-body positron emission tomography (PET) with ¹⁸F-fluorodeoxyglucose (FDG) in endometrial cancer. We aimed to assess the value of integrating FDG-PET into the management of endometrial cancer in comparison with conventional imaging alone.Methods All patients with histologically confirmed primary advanced (stage III/IV) or suspicious/documented recurrent endometrial cancer, with poor prognostic features (serum CA-125 >35 U/ml or unfavourable cell types), or surveillance after salvage therapy were eligible. Before FDG-PET scanning, each patient had received magnetic resonance imaging and/or computed tomography (MRI-CT). The receiver operating characteristic curve method with calculation of the area under the curve (AUC) was used to compare the diagnostic efficacy. Clinical impacts were determined on a scan basis.Results Forty-nine eligible patients were accrued and 60 studies were performed (27 primary staging, 33 post-therapy surveillance or restaging on relapse). The clinical impact was positive in 29 (48.3%) of the 60 scans. Mean standardised uptake values (SUVs) of true-positive lesions were 13.2 (range 5.7–37.4) for central pelvic lesions and 11.1 (range 1.5–37.4) for metastases. The sensitivity of FDG-PET alone (P<0.0001) or FDG-PET plus MRI-CT (P<0.0001) was significantly higher than that of MRI-CT alone in overall lesion detection. FDG-PET plus MRI-CT was significantly superior to MRI-CT alone in overall lesion detection (AUC 0.949 vs 0.872; P=0.004), detection of pelvic nodal/soft tissue metastases (P=0.048) and detection of extrapelvic metastases (P=0.010), while FDG-PET alone was only marginally superior by AUC (P=0.063).Conclusion Whole-body FDG-PET coupled with MRI-CT facilitated optimal management of endometrial cancer in well-selected cases.These data were presented in part at the Tenth Biennial Meeting of the International Gynecologic Cancer Society, Edinburgh, Scotland, October 3–7, 2004     

11C-methionine PET as a prognostic marker in patients with glioma: comparison with 18F-FDG PET

Purpose The purpose of this study was to compare the prognostic value of ¹¹C-methionine (MET) and ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in glioma patients.Methods The study population comprised 47 patients with gliomas (19 glioblastoma, 28 others). Pretreatment magnetic resonance imaging, MET PET and FDG PET were performed within a time interval of 2 weeks in all patients. The uptake ratio and standard uptake values were calculated. Univariate and multivariate analyses were done to determine significant prognostic factors. Ki-67 index was measured by immunohistochemical staining, and compared with FDG and MET uptake in glioma.Results Among the several clinicopathological prognostic factors, tumour pathology (glioblastoma or not), age (60 or <60 years), Karnofsky performance status (KPS) (70 or <70) and MET PET (higher uptake or not compared with normal cortex) were found to be significant predictors by univariate analysis. In multivariate analysis, tumour pathology, KPS and MET PET were identified as significant independent predictors. The Ki-67 proliferation index was significantly correlated with MET uptake (r=0.64), but not with FDG uptake.Conclusion Compared with FDG PET in glioma, MET PET was an independent significant prognostic factor and MET uptake was correlated with cellular proliferation. MET PET may be a useful biological prognostic marker in glioma patients.     

<Superscript>11</Superscript>C-acetate PET imaging of lung cancer: comparison with <Superscript>18</Superscript>F-FDG PET and <Superscript>99m</Superscript>Tc-MIBI SPET

Recently carbon-11 acetate (AC) positron emission tomography (PET) has been reported to be of clinical value for the diagnosis of cancer that is negative on fluorine-18 fluorodeoxyglucoce (FDG) PET. We investigated the uptake of AC in lung cancer to determine whether this tracer is of potential value for tumour detection and characterisation, and to compare AC PET imaging with FDG PET and technetium-99m sestamibi (MIBI) single-photon emission tomography (SPET). Twenty-three patients with 25 lung cancers underwent AC and FDG PET. Twenty of 23 patients were also investigated with MIBI SPET. Dynamic images were acquired for 26 min after the injection of 555 MBq of AC. Standardised uptake values (SUVs) and/or tumour to non-tumour activity ratios (T/N) for each tumour were investigated at 10–20 min after AC administration, 40–60 min after administration of 185 MBq FDG and 15–45 min after administration of 555 MBq MIBI. Twenty lung cancers were resected surgically, and the degree of tracer uptake in the primary lesion was correlated with histopathological features (cell dedifferentiation and aggressiveness) and prognosis. Rapid uptake of AC followed by extremely slow clearance was observed. For the purpose of tumour identification, AC PET was inferior to FDG PET in 8 of 25 (32%) lung cancers, and the T/N of AC was lower than that of FDG. However, AC PET was superior to FDG PET in the identification of a slow-growing tumour (bronchiolo-alveolar carcinoma). There was a positive correlation between AC uptake (T/N) and MIBI uptake (T/N) (r=0.799, P<0.0001). A positive correlation was not observed between either AC or MIBI uptake and the degree of cell dedifferentiation in lung adenocarcinomas, whereas FDG uptake did correlate with the degree of cell dedifferentiation. In lung adenocarcinoma, there was a weak correlation between aggressiveness and FDG uptake, but no correlation was evident for AC and MIBI. In addition, a positive correlation was not observed between AC or MIBI uptake and postoperative recurrence in lung adenocarcinoma, whereas FDG uptake did correlate with postoperative recurrence. Thus, the greater the FDG uptake, the higher the malignant grade. In conclusion, for the purpose of tumour identification, AC PET was inferior to FDG PET but superior to MIBI SPET. Neither AC nor MIBI uptake reflects the malignant grade in lung adenocarcinoma, whereas FDG uptake does. AC PET is less diagnostically informative than FDG PET in patients with lung cancer. However, AC PET may play a complementary role in the identification of low-grade malignancies that are not FDG avid.     

Comparison of 18F-FDG and 68Ga PET imaging in the assessment of experimental osteomyelitis due to Staphylococcus aureus

Purpose Although positron emission tomography (PET) using 2-[¹⁸F]fluoro-2-deoxy-D-glucose (¹⁸F-FDG) is a promising imaging modality for bone infections, the technique may still give false-positive results due to unspecific uptake in healing bone. This experimental study compared ¹⁸F-FDG and ⁶⁸Ga in PET imaging of osteomyelitis and normal bone healing.Methods A diffuse osteomyelitis model of the tibia was applied in the rat (n=50). Two weeks after operation, PET imaging with ¹⁸F-FDG and ⁶⁸Ga was performed, followed by peripheral quantitative computed tomography (pQCT) and radiography. Osteomyelitis was verified by quantitative bacteriology. In addition to in vivo imaging, ex vivo measurements of tissue radioactivity were performed to verify uptake of the tracers.Results Compared with controls with normal bone healing, the osteomyelitic tibias showed increased SUV ratios (i.e. radioactivity ratios between the operated and non-operated sides) for both ¹⁸F-FDG (1.74±0.37) and ⁶⁸Ga (1.62±0.28) (P<0.001). Ex vivo measurements also showed increased tracer accumulation in the infected bone (P=0.003 for ¹⁸F-FDG and P<0.001 for ⁶⁸Ga). The intensity of ⁶⁸Ga uptake reflected pathological changes of osteomyelitic bones measured by pQCT. The uptake of ¹⁸F-FDG, however, did not show as close a correlation with the anatomical changes. The healing bones without infection exhibited slightly elevated uptake of ¹⁸F-FDG (SUV ratio 1.16±0.06), but ⁶⁸Ga did not accumulate in the healing bone, as judged on the basis of both in vivo imaging (SUV ratio 1.02±0.05) and ex vivo measurements (SUV 0.92±0.21) (P=0.003 and P=0.022 compared with ¹⁸F-FDG uptake, respectively).Conclusion This study suggests the feasibility of ⁶⁸Ga PET imaging of bone infections. However, further studies are needed to clarify the value of ⁶⁸Ga PET for clinical purposes.     

Multifocal Colonic Lesions Detected by 18F-FDG PET/CT: Correlation with Histopathology and Gross Specimen

A 73-year-old man underwent ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) for the staging of colon cancer. The ¹⁸F-FDG PET/CT revealed three colonic lesions. The histopathologic examination of the postoperative gross specimen revealed a tubular adenoma, a tubulovillous adenoma and an adenocarinoma. The maximal standardized uptake value (SUVmax) of a tubulovillous adenoma was much higher than that of adenocarcinoma. This patient could be considered as a representative case highlighting that SUVmax is not a reliable indicator for discriminating colon cancer from colonic adenomas.     

Impact of Nonosseous Findings on 18F-NaF PET/CT in a Patient with Ductal Breast Carcinoma

¹⁸F-NaF was used as a bone-seeking PET tracer for skeletal imaging until the introduction of the widely available ^99mTc-labeled bone agents. However, there is renewed clinical interest in ¹⁸F-NaF since prior technical and logistic limitations to its routine use are no longer present, and, as a consequence, it is likely that uptake unrelated to bone and non-osseous findings will be encountered more frequently. As a result of tumoral necrosis, soft tissue metastases may demonstrate ¹⁸F-NaF avidity due to dystrophic calcification. On the other hand, all non-osseous findings, whether ¹⁸F-NaF avid or not, may provide important diagnostic information that may alter the course of the disease, including treatment options. Herein we present a patient with ductal carcinoma of the breast in whom findings unrelated to the skeletal system in ¹⁸F-NaF PET/CT altered the treatment strategy.     

18F-Fluorodeoxyglucose PET/CT in a Patient with Esophageal and Genital Leiomyomatosis

Diffuse esophageal leiomyomatosis is a rare benign tumor, which can be associated with leiomyoma in female genital tracts involving the uterus, vagina, and vulva. Alport syndrome, an inherited disorder that includes the kidneys, eyes, and sensorineural hearing loss, is also rarely associated with these multiple leiomyomatosis. In our case, ¹⁸F-fluoroseoxyglucose positron emission tomography/computed tomography was used to distinguish esophageal and genital leiomyomatosis from malignant masses.