<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.     

Brown adipose tissue: Evaluation with<Superscript>201</Superscript>Tl and<Superscript>99m</Superscript>Tc-sestamibi dual-tracer SPECT

Brown adipose tissue is one kind of adipose tissue and regulates body temperature and balance of energy via non-shivering thermogenesis. The authors present a case that strongly suggested the presence of activated brown adipose tissue in the neck, shoulders and axillary space by increased 18F-FDG uptake. 99mTc-sestamibi and 201Tl dual-tracer SPECT study showed increased 99mTc-sestamibi uptake and non-increased 201Tl uptake in the corresponding 18F-FDG uptake sites. Brown adipose tissue has dense mitochondria in the cells, which play an important role in thermogenesis. 99mTc-sestamibi uptake and retention depend on the mitochondrial activity but 201Tl uptake does not. Therefore, the activity of mitochondria in activated brown adipose tissue may explain the discrepant uptake between 99mTc-sestamibi and 201Tl.     

Pre-operative localisation of hyperfunctional parathyroid tissue with <Superscript>11</Superscript>C-methionine PET

Purpose Previous studies have shown high sensitivity of positron emission tomography (PET) with ¹¹C-methionine in the pre-operative localisation of parathyroid adenoma and hyperplasia. Nonetheless, in secondary and tertiary hyperparathyroidism (HPT) and in patients with recurrent disease, pre-operative localisation of adenomatous (PTA) or hyperplastic tissue is still a problem with all available methods. The aim of this study was to define the optimal imaging protocol and to compare the diagnostic value of ¹¹C-methionine PET and ^99mTc-methoxyisobutylisonitrile (MIBI) single-photon emission computed tomography (SPECT): in particular, we wished to define the benefit of ¹¹C-methionine in those patients with inconclusive or negative conventional imaging.Methods Thirty highly pre-selected patients with HPT were enrolled. Sixteen patients had primary HPT, 12 patients had secondary HPT, and two patients had recurrences of parathyroid carcinomas. All patients had ultrasound of the neck, dual-phase scintigraphy with ^99mTc-MIBI and PET with ¹¹C-methionine. SUV_parathyroid/SUV_{cervical soft tissue} (target-to-background) and SUV_{parathyroid tissue}/SUV_{thyroid tissue} (target-to-non-target) ratios were calculated. After surgery, histology of specimens was obtained in all patients but one.Results In 12 patients with secondary or tertiary HPT, 36 hyperplastic parathyroid glands were histologically verified. Twenty-five of 36 lesions (69%) were detected with ¹¹C-methionine PET and 17 (47%) with ^99mTc-MIBI scintigraphy. PET studies were positive in 17/18 (94%) cases in which HPT was related to adenomas or carcinomas. ^99mTc-MIBI scintigraphy/SPECT yielded pathological lesions in 9/18 cases (50%). All eight atypical localisations of parathyroid glands were detected with PET but only six of the eight were detected with ^99mTc-MIBI scintigraphy/SPECT. In 10/11 patients with recurrent HPT and non-diagnostic scintigraphy/SPECT, hyperfunctional parathyroid tissue was identified with ¹¹C-methionine PET. The highest SUV_parathyroid/SUV_{cervical soft tissue} ratio was found 10 min, and the highest SUV_{parathyroid tissue}/SUV_{thyroid tissue} ratio 40 min post injection. In three patients clear delineation of hyperfunctional tissue was only achieved after 40 min post injection.Conclusion ¹¹C-methionine PET is a clinically useful method in highly pre-selected patients with recurrent primary HPT as well as in secondary and tertiary HPT if ultrasound and ^99mTc-MIBI SPECT are inconclusive or negative. PET imaging of atypical PTA localisations is more accurate than conventional scintigraphy. In order to achieve optimal contrast of parathyroid glands versus thyroid tissue and adjacent soft tissue, imaging at both 10 min and 40 min is recommended.     

Regional differences between <Superscript>99m</Superscript>Tc-ECD and <Superscript>99m</Superscript>Tc-HMPAO SPET in perfusion changes with age and gender in healthy adults

A number of studies using single-photon emission tomography (SPET) have shown perfusion changes with age in several cortical and subcortical areas, which might distort the results of perfusion imaging studies of neuropsychiatric disorders. Technetium-99m labelled ethyl cysteinate dimer (ECD) and hexamethylpropylene amine oxime (HMPAO) are both used as markers of cerebral perfusion, but have different pharmacokinetics and retention patterns. The aim of this study was to determine whether age and gender effects on perfusion SPET differ depending on whether ^99mTc-HMPAO or ^99mTc-ECD is used. Forty-five subjects (20 male and 25 female, mean age 52.8±6.6 years) were assigned to ^99mTc-HMPAO SPET (HMPAO group), and 39 subjects (24 male and 15 female, mean age 52.6±6.7 years) to ^99mTc-ECD SPET (ECD group). SPET images were obtained about 10 min after intravenous injection of approximately 800 MBq ^99mTc-HMPAO or ^99mTc-ECD using the same SPET scanner. Three-dimensional volumetric magnetic resonance imaging was performed to as7sess morphological changes in the grey matter. All image processing and statistical analyses were performed using SPM99 software. An area in the right anterior frontal lobe showed an increase in perfusion with age only in the HMPAO group, whereas areas in the bilateral retrosplenial cortex showed decreases in perfusion with age only in the ECD group; neither group showed corresponding changes in the grey matter. The present study shows that different effects of age on perfusion are observed depending on whether ^99mTc-HMPAO and ^99mTc-ECD is used. This suggests that the results of perfusion SPET are differently confounded depending on the tracer used, and that perfusion SPET with these tracers has limitations when used in research on subtle perfusion changes.     

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.     

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.     

Single-photon agents for tumor imaging:<Superscript>201</Superscript>TI,<Superscript>99m</Superscript>Tc-MIBI,and<Superscript>99m</Superscript>Tc-tetrofosmin

This review aims at fostering comprehension and knowledge not only for expert physicians who can skillfully handle various techniques for tumor imaging but also for young practitioners in the field of nuclear medicine. As image processing software and hardware become smaller, faster and better, SPECT will adapt and incorporate these advances. A principal advantage of SPECT over PET is the more widespread availability of the equipment and lower cost for the introduction of the system in community-based facilities. Moreover, SPECT has become less dependent on a limited number of acknowledged experts for its interpretation owing to a variety of handy computer tools for imaging analyses. The increasing use of PET in tumor imaging is not necessarily proportional to the decline of SPECT. General physicians' attention to SPECT technology would also increase more by evoking their interest in "tracer imaging."     

Correlation of <Superscript>18</Superscript>F-FLT and <Superscript>18</Superscript>F-FDG uptake on PET with Ki-67 immunohistochemistry in non-small cell lung cancer

Purpose The nucleoside analogue 3′-deoxy-3′-¹⁸F-fluorothymidine (FLT) has recently been introduced for imaging cell proliferation with positron emission tomography (PET). We prospectively evaluated whether FLT uptake reflects proliferative activity as indicated by the Ki-67 index in non-small cell lung cancer (NSCLC), in comparison with 2-deoxy-2-¹⁸F-fluoro-D-glucose (FDG). Methods A total of 18 patients with newly diagnosed NSCLC were examined with both FLT PET and FDG PET. PET imaging was performed at 60 min after each radiotracer injection. Tumour lesions were identified as areas of focally increased uptake, exceeding background uptake in the lungs. For semi-quantitative analysis, the maximum standardised uptake value (SUV) was calculated. Proliferative activity as indicated by the Ki-67 index was estimated in tissue specimens. Immunohistochemical findings were correlated with SUVs. Results The sensitivity of FLT and FDG PET for the detection of lung cancer was 72% and 89%, respectively. Four of the five false-negative FLT PET findings occurred in bronchiolo-alveolar carcinoma. The mean FLT SUV was significantly lower than the mean FDG SUV. A significant correlation was observed between FLT SUV and Ki-67 index (r = 0.77; p < 0.0002) and for FDG SUV (r = 0.81; p < 0.0001). Conclusion The results of this preliminary study suggest that, compared with FDG, FLT may be less sensitive for primary staging in patients with NSCLC. Although FLT uptake correlated significantly with proliferative activity in NSCLC, the correlation was not better than that for FDG uptake.     

Normal uptake of <Superscript>18</Superscript>F-FDG in the testis: an assessment by PET/CT

Objective The aim of this study was to assess the physiological uptake of ¹⁸F-fluoro-2-deoxyglucose (FDG) by an apparently normal testis with combined positron emission tomography–computed tomography (PET/CT) and its correlation with age, blood glucose level, and testicular volume. Methods The testicular uptake of ¹⁸F-FDG, expressed as the standardized uptake value (SUV), was measured on PET/CT images in 203 men. The correlation between SUV and age, blood glucose level, and testicular volume was assessed. Results The SUV in the total of 406 testes was 2.44 ± 0.45 (range 1.23–3.85). The SUV was 2.81 ± 0.43 (2.28–3.85) for 30–39 years (n = 12), 2.63 ± 0.45 (1.77–3.75) for 40–49 years (n = 64), 2.46 ± 0.35 (1.44–3.15) for 50–59 years (n = 82), 2.51 ± 0.41 (1.50–3.46) for 60–69 years (n = 86), 2.43 ± 0.47 (1.42–3.29) for 70–79 years (n = 86), and 2.18 ± 0.45 (1.23–3.03) for 80–89 years (n = 76). When we calculated the mean SUV of bilateral testes in each patient, there were significant statistical differences between those in the age group of 30–39 years and 80–89 years, 40–49 years and 80–89 years, and 50–60 years and 80–89 years, when using an unpaired test with Bonferroni correction. The laterality index (|L − R|/(L + R) × 2) in 203 men was 0.066 ± 0.067 (0–0.522). There was a mild correlation between the mean SUV and age (r = −0.284, P < 0.001) as well as between the mean SUV and mean volume (r = +0.368, P < 0.001). There was no correlation between the mean SUV and glucose blood level (r = −0.065, P = 0.358). Conclusions Some uptake of FDG is observed in the normal testis and declines slightly with age. Physiological FDG uptake in the testis should not be confused with pathological accumulation.     

Comparison of whole-body <Superscript>18</Superscript>F-FDG PET, <Superscript>99m</Superscript>Tc-MIBI SPET,and post-therapeutic <Superscript>131</Superscript>I-Na scintigraphy in the detection of metastatic thyroid cancer

The usefulness of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in differentiated thyroid cancer (DTC) has been demonstrated by many investigators, but in only a small number of studies have FDG-PET images been compared with those obtained using other non-iodine tumour-seeking radiopharmaceuticals. In most of the studies, planar imaging was performed for comparison using thallium-201 chloride or technetium-99m 2-methoxyisobutylisonitrile (^99mTc-MIBI). Furthermore, FDG-PET studies were not always performed in the hypothyroid state with increased levels of thyroid stimulating hormone (TSH), which are known to increase FDG uptake by DTC. The aim of this study was to compare the ability of FDG-PET to detect metastatic DTC with that of ^99mTc-MIBI whole-body single-photon emission tomography (SPET) and post-therapeutic iodine-131 scintigraphy, evaluated under TSH stimulation. Nineteen patients (8 men, 11 women; age range, 38–72 years, mean 60 years; 17 thyroidectomised and 2 inoperable patients following ¹³¹I ablation of the remaining thyroid tissue; 16 papillary and 3 follicular carcinomas) with metastatic DTC underwent FDG-PET whole-body scan (WBS) and ^99mTc-MIBI SPET WBS at an interval of less than 1 week, followed by ¹³¹I therapy. The SPET images were reconstructed using the maximum likelihood expectation maximisation (ML-EM) method. All patients were hypothyroid at the time of each scan. ¹³¹I WBS was performed 3–5 days after oral administration of the therapeutic dose. A total of 32 lesions [10 lymph node (LN), 15 lung, 6 bone, 1 muscle] were diagnosed as metastases, as confirmed by histopathology and/or other imaging modalities (X-ray, US, CT, MRI, bone, ²⁰¹Tl and ¹³¹I scans). FDG-PET, ^99mTc-MIBI SPET and post-therapeutic ¹³¹I scintigraphy respectively revealed a total of 26 (81.3%), 20 (62.5%) and 22 (68.8%) lesions. These techniques respectively demonstrated nine (90.0%), eight (80.0%) and six (60.0%) LN metastases, and eleven (73.3%), seven (46.7%) and ten (66.7%) lung metastases. They each demonstrated five of the six bone metastases (83.3%). FDG-PET and ^99mTc-MIBI SPET were positive in 17 (78.3%) and 14 (63.6%) of the 22 ¹³¹I-positive lesions, respectively, and also in nine (90.0%) and six (60.0%) of the ten ¹³¹I-negative lesions, respectively. Three of the five ¹³¹I-positive and FDG-PET-negative lesions were miliary type lung metastases with a maximal nodular diameter of less than 10 mm. Comparison of FDG-PET with ^99mTc-MIBI SPET revealed concordant results in 24 lesions, and discordant results in eight lesions (seven with positive FDG-PET alone and one with positive ^99mTc-MIBI SPET alone). In conclusion: (a) even using whole-body SPET, FDG PET is superior to ^99mTc-MIBI in terms of ability to detect metastases of DTC; (b) the higher sensitivity of FDG-PET compared with the previous studies could partly be due to increased serum TSH.     

Optimal dose of <Superscript>18</Superscript>F-FDG required for whole-body PET using an LSO PET camera

Reducing the acquisition time of whole-body fluorine-18 fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) (corrected for attenuation) is of major importance in clinical practice. With the introduction of lutetium oxyorthosilicate (LSO), the acquisition time can be dramatically reduced, provided that patients are injected with larger amounts of tracer and/or the system is operated in 3D mode. The aim of this study was to determine the optimal dose of ¹⁸F-FDG required in order to achieve good-to-excellent image quality when a "3-min emission, 2-min transmission/bed position" protocol is used for an LSO PET camera. A total of 218 consecutive whole-body ¹⁸F-FDG PET studies were evaluated retrospectively. After excluding patients with liver metastases, hyperglycaemia and paravenous injections, the final study population consisted of 186 subjects (112 men, 74 women, age 59±15 years). Patients were injected with an activity of ¹⁸F-FDG ranging from 2.23 to 15.21 MBq/kg. Whole-body images corrected for attenuation (3 min emission, 2 min transmission/bed position) were acquired with an LSO PET camera (Ecat Accel,Siemens) 60 min after tracer administration. Patients were positioned with their arms along the body. Image reconstruction was done iteratively and a post-reconstruction filter was applied. Image quality was scored visually by two independent observers using a five-point scoring scale (poor, reasonable, good, very good, excellent). In addition, the coefficient of variability (COV) was measured in a region of interest over the liver in order to quantify noise. Of the images obtained in 118 patients injected with 8 MBq/kg ¹⁸F-FDG, 92% and 90% were classified as good, very good or excellent by observer 1 and observer 2, respectively. The COV averaged 10.63%±3.19% for doses 8 MBq/kg and 16.46%±5.14% for doses <8 MBq/kg. Administration of an ¹⁸F-FDG dose of 8 MBq/kg results in images of good to excellent quality in the vast majority of patients when using an LSO PET camera and applying a 3-min emission, 2-min transmission/bed position acquisition protocol. At lower doses, a rapid decline in image quality and increasing noise are observed. Alternative protocols should be adopted in order to compensate for the loss in image quality when doses <8 MBq/kg are used.     

<Superscript>11</Superscript>C-methionine (MET) and <Superscript>18</Superscript>F-fluorothymidine (FLT) PET in patients with newly diagnosed glioma

Purpose  The purpose of this prospective study was to clarify the individual and combined role of l-methyl-¹¹C-methionine-positron emission tomography (MET-PET) and 3′-deoxy-3′-[¹⁸F]fluorothymidine (FLT)-PET in tumor detection, noninvasive grading, and assessment of the cellular proliferation rate in newly diagnosed histologically verified gliomas of different grades. Materials and methods  Forty-one patients with newly diagnosed gliomas were investigated with MET-PET before surgery. Eighteen patients were also examined with FLT-PET. MET and FLT uptakes were assessed by standardized uptake value of the tumor showing the maximum uptake (SUV_max), and the ratio to uptake in the normal brain parenchyma (T/N ratio). All tumors were graded by the WHO grading system using surgical specimens, and the proliferation activity of the tumors were determined by measuring the Ki-67 index obtained by immunohistochemical staining. Results  On semiquantitative analysis, MET exhibited a slightly higher sensitivity (87.8%) in tumor detection than FLT (83.3%), and both tracers were 100% sensitive for malignant gliomas. Low-grade gliomas that were false negative on MET-PET also were false negative on FLT-PET. Although the difference of MET SUV_max and T/N ratio between grades II and IV gliomas was statistically significant (P < 0.001), there was a significant overlap of MET uptake in the tumors. The difference of MET SUV_max and T/N ratio between grades II and III gliomas was not statistically significant. Low-grade gliomas with oligodendroglial components had relatively high MET uptake. The difference of FLT SUV_max and T/N ratio between grades III and IV gliomas was statistically significant (P < 0.01). Again, the difference of FLT SUV_max and T/N ratio between grades II and III gliomas was not statistically significant. Grade III gliomas with non-contrast enhancement on MR images had very low FLT uptake. In 18 patients who underwent PET examination with both tracers, a significant but relatively weak correlation was observed between the individual SUV_max of MET and FLT (r = 0.54, P < 0.05) and T/N ratio of MET and FLT (r = 0.56, P < 0.05). Total FLT uptake in the tumor had a higher correlation (r = 0.89, P < 0.001) with Ki-67 proliferation index than MET uptake (r = 0.49, P < 0.01). Conclusions  PET studies using MET and FLT are useful for tumor detection in newly diagnosed gliomas. However, there is no complimentary information in tumor detection with simultaneous measurements of MET- and FLT-PET in low grade gliomas. FLT-PET seems to be superior than MET-PET in noninvasive tumor grading and assessment of proliferation activity in gliomas of different grades.     

The role of <Superscript>18</Superscript>F-FDG PET in characterising disease activity in Takayasu arteritis

Takayasu arteritis (TA) is a rare, sporadic and chronic inflammatory arteritis, which predominantly affects the aorta and its branches. Diagnosis can be difficult and there are limitations to the current diagnostic work-up. By detecting areas of active glucose metabolism present in active vasculitis, imaging with fluorine-18 fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) could potentially have a role in the management of TA. Our aim was to assess this role by reviewing 28 ¹⁸F-FDG PET scans performed on 18 patients suspected of having TA. All patients had full clinical and laboratory assessment, cross-sectional imaging and angiography, and 16/18 satisfied the American College of Rheumatologists criteria for TA. ¹⁸F-FDG PET achieved a sensitivity of 92%, a specificity of 100%, and negative and positive predictive values of 85% and 100% respectively in the initial assessment of active vasculitis in TA. We conclude that ¹⁸F-FDG PET can be used to diagnose early disease, to detect active disease (even within chronic changes) and to monitor the effectiveness of treatment.     

Reduction of <Superscript>99m</Superscript>Tc-sestamibi and <Superscript>99m</Superscript>Tc-tetrofosmin uptake in MRP-expressing breast cancer cells under hypoxic conditions is independent of MRP function

Hypoxia reduces the uptake of technetium-99m sestamibi (MIBI) in human cancer cell lines. In the current investigation, we attempted to identify the relationship between hypoxia-induced alteration of ^99mTc-MIBI accumulation and expression of multi-drug resistance-associated protein (MRP) in the MCF7/WT breast cancer cell line and its subclonal cell line, MCF7/VP, which expresses high levels of MRP1. A second cationic compound, ^99mTc-tetrofosmin (TF), was also examined. Cellular uptake of ^99mTc-MIBI and ^99mTc-TF was significantly higher in parental MCF7/WT cells than in MCF7/VP cells. Hypoxic conditions generated with a mixture of 95% N₂ and 5% CO₂ reduced cellular uptake of the two tracers in both parental MCF7/WT cells and MRP1-expressing MCF7/VP cells. Cell binding assay with iodine-125-labelled anti-MRP1 antibody demonstrated its specific binding to MCF7/VP cells. Hypoxia did not affect the amount of antibody bound to MCF7/VP cells. These results indicate that hypoxia-induced reduction of tracer uptake in tumour cells is a phenomenon independent of MRP function.     

High and typical <Superscript>18</Superscript>F-FDG bowel uptake in patients treated with metformin

Purpose This prospective and bi-centric study was conducted in order to determine the impact of antidiabetic treatments (AD) on ¹⁸F-FDG bowel uptake in type 2 diabetic patients. Methods Fifty-five patients with previously diagnosed and treated type 2 diabetes mellitus (group 1) were divided in two subgroups: AD treatment including metformin (n=32; group 1a) and AD treatment excluding metformin (n=23; group 1b). The 95 patients without diabetes mellitus made up controls (group 2). ¹⁸F-FDG uptake in small intestine and colon was visually graded and semi-quantitatively measured using the maximum standardized uptake value. Results ¹⁸F-FDG bowel uptake was significantly increased in AD patients (group 1) as compared to controls (group 2) (p<0.001). Bowel uptake was significantly higher in AD patients including metformin (group 1a) as compared to AD patients excluding metformin (group 1b) (p<0.01), whose bowel uptake was not significantly different from controls (group 2). A metformin treatment was predictive of an increased bowel uptake in the small intestine (odds ratio OR=16.9, p<0.0001) and in the colon (OR=95.3, p<0.0001), independently of the other factors considered in the multivariate analysis. Bowel uptake pattern in the patients treated with metformin was typically intense, diffuse and continuous along the bowel, strongly predominant in the colon, in both the digestive wall and lumen. Conclusion This study emphasizes that metformin significantly increases ¹⁸F-FDG uptake in colon and, to a lesser extent, in small intestine. It raises the question of stopping metformin treatment before an ¹⁸F-FDG PET/CT scan is performed for intra-abdominal neoplasic lesion assessment.     

The effects of <Superscript>99m</Superscript>Tc-HMPAO-labelled leucocyte scan on human karyotype

Technetium-99m hexamethylpropylene amine oxime (HMPAO) white blood cell scan (WBCS) requires separation and labelling of mixed leucocytes, which include particularly radiosensitive cells, lymphocytes. Lymphocytes labelled during the mixed leucocyte labelling procedure could represent a problem for patients owing to the possible induction of chromosomal aberrations. Lymphocytes labelled in mixed leucocyte preparations are probably killed by the high-dose radiation. Nevertheless, it has been reported that some of these lymphocytes can proliferate after in vitro stimulation. If these cells were to reproduce themselves in vivo, onset of, or increase over time in, chromosomal aberrations could occur on peripheral blood lymphocytes. The present study was performed on 21 patients who underwent WBCS for suspected infection/inflammation. Blood samples of these patients were submitted to cytogenetic study, comprising karyotype determination, evaluation of sister chromatid exchanges (SCE) and evaluation of induced chromosomal breakages or rearrangement rate (B/R). This study was performed 2 h before and 7 days and 6 months after the WBCS. The results demonstrated no statistically significant differences between SCE and B/R values before and after WBCS. No cause-effect relationship appeared to exist between WBCS and the onset of chromosomal aberrations in peripheral blood lymphocytes, at least during the first 6 months post WBCS and within the limits of this study's approach. The high-dose radiation administered to lymphocytes was almost certainly sufficient to kill these cells.     

<Superscript>99m</Superscript>Tc-HYNIC octreotide in neuroblastoma

Disease status assessment of neuroblastoma patients requires computed tomography (or magnetic resonance imaging), bone scan, metaiodobenzylguanidine (MIBG) scan, bone marrow tests, and urine catecholamine measurements. There is no clinical experience concerning the evaluation of these patients by means of technetium-99m (^99mTc)-somatostatin analog scintigraphy. Furthermore, these radiopharmaceuticals are promising imaging agents owing to their lower cost, availability, dosimetry, and ease of preparation. An 8-year-old boy already diagnosed with stage-IV neuroblastoma received chemotherapy. In the follow-up, after obtaining the parents’ informed consent, iodin 131 (¹³¹I)-MIBG and ^99mTc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-octreotide scans were done on separate days to evaluate tumor extension. Even as the ¹³¹I-IBG scan showed mild diffuse uptake in the projection of both lung hili, the ^99mTc-HYNIC-octreotide scan showed multiple axial and appendicular bone uptakes and paravertebral, abdominal, mediastinal, and supraclavicular ganglionar uptakes. The ^99mTc-HYNIC-octreotide showed much more lesion extension than the ¹³¹I-MIBG. Therefore, ^99mTc-HYNIC-octreotide may be a promising radiopharmaceutical for the evaluation of neuroblastoma patients. This finding justifies the pre liminary evaluation of this tracer in the context of a clinical trial.     

<Superscript>99m</Superscript>Tc-ECD brain perfusion SPECT in hyperalgesic fibromyalgia

Purpose Neuro-imaging studies with ^99mTc-HMPAO SPECT in fibromyalgia (FM) patients have reported only limited subcortical hypoperfusion. ^99mTc-ECD SPECT is known to provide better evaluation of areas of high cerebral blood flow and regional metabolic rate. We evaluated a homogeneous group of hyperalgesic patients with FM using ^99mTc-ECD SPECT. The aim of this study was to investigate brain processing associated with spontaneous pain in FM patients. Methods Eighteen hyperalgesic FM women (mean age 49 years, range 25–63 years; American College of Rheumatology criteria) and ten healthy women matched for age were enrolled in the study. A voxel-by-voxel group analysis was performed using SPM2 (p<0.05, corrected for multiple comparisons). Visual Analogue Scale score for pain was 82±4 at the time of the SPECT study. Results Compared with control subjects, we observed individual brain SPECT abnormalities in FM patients, confirmed by SPM2 analysis, with hyperperfusion of the somatosensory cortex and hypoperfusion of the frontal, cingulate, medial temporal and cerebellar cortices. Conclusion In the present study, performed without noxious stimuli in hyperalgesic FM patients, we found significant hyperperfusion in regions of the brain known to be involved in the sensory dimension of pain processing and significant hypoperfusion in areas assumed to be associated with the affective-attentional dimension. As current pharmacological and non-pharmacological therapies act differently on the two components of pain, we hypothesise that SPECT could be a valuable and readily available tool to guide individual therapeutic strategy and provide objective follow-up of pain processing recovery under treatment.     

Abnormal retention of<Superscript>99m</Superscript>Tc-TF in a hamster model of cardiomyopathy analyzed by<Superscript>99m</Superscript>Tc-TF and<Superscript>125</Superscript>I-BMIPP autoradiography

OBJECTIVE: Enhanced washout of 99mTc-tetrofosmin (TF) has been reported in patients with hypertrophic cardiomyopathy (HCM). Here, using quantitative dual-autoradiography, the relationship between TF retention abnormality and metabolism depicted by 125I-BMIPP uptake was investigated quantitatively in a hamster model of cardiomyopathy. METHODS AND RESULTS: Early and delayed TF images were obtained at 5 min (7 cardiomyopathic and 5 normal hamsters) and 60 min (8 cardiomyopathic and 5 normal hamsters) after injection, respectively. BMIPP image was obtained 5 min after injection. Five cardiomyopathic and 5 normal hamsters were evaluated histologically. Percent uptake of TF and BMIPP in the heart was measured by an auto-well counter. The left ventricular wall was divided into 12 segments, and the relative regional uptake of TF and BMIPP was measured for each segment. Heterogeneity of radioactive distribution was determined by the standard deviation (SD) of radioactive counts in the left ventricular wall on autoradiogram. The uptake of early TF, delayed TF, and BMIPP in cardiomyopathic hamsters was 8.8%, 20.3%, and 25.3% lower than that in normal hamsters, p < 0.05, p < 0.01, and p < 0.001, respectively. In normal hamsters, distribution of radioactivity in all images was homogeneous, and the SD values were about 13. In cardiomyopathic hamsters, heterogeneous distribution was observed on all images, and the degree of heterogeneity was marked on delayed TF and BMIPP images. The SD was 19.7 +/- 1.2 for early TF image, 25.5 +/- 1.4 for delayed TF image, and 31.7 +/- 2.4 for BMIPP image, respectively. A weak linear correlation was observed between the relative regional uptake of the delayed TF and BMIPP in cardiomyopathic hamsters (r = 0.57). Electron microscopy demonstrated ultra-structural changes in mitochondria of cardiomyopathic hamsters. CONCLUSION: Degree of retention abnormality on delayed TF image corresponded to the metabolic abnormality, probably due to mitochondrial dysfunction, depicted on BMIPP imaging.     

<Superscript>18</Superscript>F-FDG PET,genotype-corrected ACE and sIL-2R in newly diagnosed sarcoidosis

Purpose  Angiotensin-converting enzyme (ACE) and soluble interleukin-2 receptor (sIL-2R) are serological markers, widely used for determining sarcoidosis activity. ¹⁸F-FDG PET has proven to be a sensitive technique in the imaging of sarcoidosis. The aim of this study was to determine sensitivity of ¹⁸F-FDG PET, genotype-corrected ACE and sIL-2R in active sarcoidosis as well as their correlation. Methods  This retrospective study included 36 newly diagnosed, symptomatic sarcoidosis patients. ACE and sIL-2R levels were simultaneously obtained within 4 weeks of ¹⁸F-FDG PET. ACE was corrected for genotype and expressed as Z-score. ¹⁸F-FDG PET was visually evaluated and scored as positive or negative. Maximum and average standardized uptake values (SUV_max and SUV_avg) were compared with ACE and sIL-2R. Results   ¹⁸F-FDG PET was found positive in 34 of 36 patients (94%). Thirteen patients (36%) showed an increased ACE with the highest sensitivity found in patients with the I/I genotype (67%). Seventeen patients (47%) showed an increased sIL-2R. No correlation was found between SUV and ACE or sIL-2R. Increased ACE and sIL-2R correlated with a positive ¹⁸F-FDG PET in 12 patients (92%) and 16 patients (94%), respectively. Conclusion   ¹⁸F-FDG PET is a very sensitive technique to assess active sarcoidosis, in contrast with ACE and sIL-2R, suggesting a pivotal role for ¹⁸F-FDG PET in future sarcoidosis assessment.