Brain tumour imaging with carbon-11 choline: comparison with FDG PET and gadolinium-enhanced MR imaging.

The purpose of this study was to assess the clinical potential of methyl-11C-choline (11C-choline) in the diagnosis of brain tumours. To this end, the results of 11C-choline positron emission tomography (PET) in 22 patients suspected of having brain tumours were compared with the findings of contrast-enhanced magnetic resonance (MR) imaging and fluorine-18 fluorodeoxyglucose PET. A histopathological diagnosis was made for each patient during open surgery. The standardised uptake values of brain tumours and the tumour-to-white matter count (T/W) ratios were determined. The degree of 11C-choline accumulation noted in PET images was compared with the gadolinium-enhanced areas of MR images. The mean T/W ratio of 11C-choline in high-grade gliomas was found to be higher than that in low-grade gliomas. This difference was statistically significant (mean+/-SD: 8.7+/-6.2, n=9 versus 1.5+/-0.7, n=5, P<0.03) when data pertaining to the prominent uptake of 11C-choline in a patient with a pilocytic astrocytoma were excluded. 11C-choline PET failed to detect non-neoplastic lesions in two patients. Areas of 11C-choline accumulation in PET scans were larger than areas enhanced on MR images in five cases involving high-grade gliomas. 11C-choline PET differentiated between low-grade gliomas and high-grade gliomas, but did not differentiate between low-grade gliomas and non-neoplastic lesions. The combination of 11C-choline PET and MR imaging may provide investigators with an accurate means by which to identify high-grade gliomas.     

Uptake of iodine-123-α-methyl tyrosine by gliomas and non-neoplastic brain lesions

Using single-photon emission tomography (SPET), the radiopharmaceuticall,-3-iodine-123--methyl tyrosine (IMT) has been applied to the imaging of amino acid transport into brain tumours. It was the aim of this study to investigate whether IMT SPET is capable of differentiating between high-grade gliomas, low-grade gliomas and non-neoplastic brain lesions. To this end, IMT uptake was determined in 53 patients using the triple-headed SPET camera MULTISPECT 3. Twenty-eight of these subjects suffered from high-grade gliomas (WHO grade III or IV), 12 from low-grade gliomas (WHO grade II), and 13 from non-neoplastic brain lesions, including lesions after effective therapy of a glioma (five cases), infarctions (four cases), inflammatory lesions (three cases) and traumatic haematoma (one case). IMT uptake was significantly higher in high-grade gliomas than in low-grade gliomas and non-neoplastic lesions. IMT uptake by low-grade gliomas was not significantly different from that by non-neoplastic lesions. Diagnostic sensitivity and specificity were 71% and 83% for differentiating high-grade from low-grade gliomas, 82% and 100% for distinguishing high-grade gliomas from non-neoplastic lesions, and 50% and 100% for discriminating low-grade gliomas from non-neoplastic lesions. Analogously to positron emission tomography with radioactively labelled amino acids and fluorine-18 deoxyglucose, IMT SPET may aid in differentiating high-grade gliomas from histologically benign brain tumours and non-neoplastic brain lesions; it is of only limited value in differentiating between non-neoplastic lesions and histologically benign brain tumours.     

Validation of brain tumour imaging with p-[123I]iodo-l-phenylalanine and SPECT

Purpose The aims of this prospective study were to validate single-photon emission computed tomography (SPECT) with p-[¹²³I]iodo-l-phenylalanine (IPA) in brain tumours and to evaluate its potential for the characterisation of indeterminate brain lesions.Methods In 45 patients with indeterminate brain lesions or suspected progression of glioma, amino acid uptake was studied using IPA-SPECT and compared with the final diagnosis established by biopsy or serial imaging. After image fusion of IPA-SPECT and magnetic resonance imaging, the presence of tumour was visually determined by two independent observers. IPA uptake was quantified as the ratio between maximum uptake in the suspicious lesion and mean uptake in unaffected brain.Results Primary brain tumours were present in 35 cases (12 low-grade and 23 high-grade gliomas). Non-neoplastic brain lesions were confirmed in seven cases (three dysplasias, three inflammatory lesions, one lesion after effective therapy). Visual analysis showed a high concordance between the two observers (kappa=0.90, p<0.001), with sensitivity and specificity of 86% and 100% for the discrimination of primary brain tumours and non-neoplastic lesions. At 30 min p.i., IPA uptake in primary brain tumours was higher than that in non-neoplastic lesions (1.70±0.36 vs 1.14±0.18, p<0.05). Brain metastases showed no increased uptake (1.13±0.22, n=3). The persistent retention of IPA in low-grade gliomas without disruption of the blood–brain barrier was visualised up to 24 h p.i. Low-grade and high-grade gliomas showed equivalent IPA uptake (1.72±0.37 vs 1.67±0.36 at 30 min, p=0.745).Conclusion IPA shows long and specific retention in gliomas. IPA is a promising and safe radiopharmaceutical for the visualisation of gliomas and the characterisation of indeterminate brain lesions.     

Sequential scintigraphic strategy for the differentiation of brain tumours

Both thallium-201 and iodine-123 alpha-methyltyrosine (123I-IMT) have been shown to be useful in the diagnostic evaluation of brain tumours. The aim of this study was to investigate the respective contributions of 201Tl and 123I-IMT single-photon emission tomography (SPET) in the non-invasive evaluation of intracerebral tumours. We analysed 65 patients with the following brain tumours: 8 non-neoplastic lesions, 4 meningiomas, 12 low-grade gliomas, 28 high-grade gliomas, 11 metastases and 2 high-grade lymphomas. 201Tl SPET and 123I-IMT SPET were performed [start of 201Tl SPET: 15 min p.i. (early) and 180 min p.i. (delayed); start of 123I-IMT SPET: 15 min p.i.]. The intensity of uptake was quantified as the ratio between tracer accumulation in the tumour and in the contralateral hemisphere. None of the non-neoplastic lesions or low-grade gliomas expressed marked 201Tl uptake. All malignant tumours except one small metastasis and all meningiomas except one small, cystic and degenerated lesion showed significant 201Tl accumulation [Tl(15')>2.0]; 123I-IMT uptake was either absent or intermediate in non-malignant lesions except in two low-grade gliomas; the highest levels were observed in high-grade gliomas followed by metastases and lymphomas (mean IMT: 2.7 vs. 2.1 vs. 1.8), with metastases showing a high variability in 123I-IMT uptake (range: 0.8-3.6). Using 201Tl to distinguish non-neoplastic lesions from malignant tumours and meningiomas, 63 of 65 patients were characterised correctly. In the latter group, high-grade gliomas were correctly identified in 27 of 28 cases by their amino acid uptake. It is concluded that the combination of 201Tl and 123I-IMT surpasses the accuracy of each single test in the differentiation of space-occupying lesions of the brain. Based on these preliminary results, a sequential strategy is proposed involving an initial 201Tl SPET study and an additional 123I-IMT SPET study in the event of positive 201Tl uptake.     

Correlation between dynamic susceptibility contrast perfusion MRI and methionine metabolism in brain gliomas: preliminary results

PURPOSE: To evaluate in brain gliomas the relationship between tumor vascularity measured by MR-based maximum regional cerebral blood volume (rCBV) and tumor amino-acid metabolism based on maximum carbon-11 methionine (MET) uptake on positron emission tomography (PET). MATERIALS AND METHODS: Eighteen patients with histologically proven primary brain gliomas were included in the study. In addition to conventional MR sequences, dynamic MR images, including a first-pass gadopentetate dimeglumine T2*-weighted echo-planar perfusion sequence and a PET study using MET, were acquired. Eleven patients had low-grade gliomas, and seven had high-grade gliomas. rCBV ratios and MET uptake ratios normalized to the contralateral white matter (WM) corresponding values were measured in each tumor. Both maximum rCBV ratios and maximum MET uptake ratios were correlated to histopathology. The maximum rCBV ratios were correlated to the maximum MET uptake ratios. RESULTS: Both the maximum rCBV ratios and maximum MET uptake ratios of high-grade gliomas were significantly higher than those of low-grade gliomas (P<0.05). There was a significant positive correlation between maximum rCBV ratios and maximum MET uptake ratios (Spearman: r=0.89, P<0.00001). CONCLUSION: The maximum rCBV ratio and maximum MET uptake ratio are significantly correlated in gliomas, reflecting a close link between amino acid uptake and vascularity in these tumors.     

Sequential scintigraphic strategy for the differentiation of brain tumours

Both thallium-201 and iodine-123 α-methyltyrosine (¹²³I-IMT) have been shown to be useful in the diagnostic evaluation of brain tumours. The aim of this study was to investigate the respective contributions of ²⁰¹Tl and ¹²³I-IMT single-photon emission tomography (SPET) in the non-invasive evaluation of intracerebral tumours. We analysed 65 patients with the following brain tumours: 8 non-neoplastic lesions, 4 meningiomas, 12 low-grade gliomas, 28 high-grade gliomas, 11 metastases and 2 high-grade lymphomas. ²⁰¹Tl SPET and ¹²³I-IMT SPET were performed [start of ²⁰¹Tl SPET: 15 min p.i. (early) and 180 min p.i. (delayed); start of ¹²³I-IMT SPET: 15 min p.i.]. The intensity of uptake was quantified as the ratio between tracer accumulation in the tumour and in the contralateral hemisphere. None of the non-neoplastic lesions or low-grade gliomas expressed marked ²⁰¹Tl uptake. All malignant tumours except one small metastasis and all meningiomas except one small, cystic and degenerated lesion showed significant ²⁰¹Tl accumulation [Tl(15’)>2.0]; ¹²³I-IMT uptake was either absent or intermediate in non-malignant lesions except in two low-grade gliomas; the highest levels were observed in high-grade gliomas followed by metastases and lymphomas (mean IMT: 2.7 vs 2.1 vs 1.8), with metastases showing a high variability in ¹²³I-IMT uptake (range: 0.8–3.6). Using ²⁰¹Tl to distinguish non-neoplastic lesions from malignant tumours and meningiomas, 63 of 65 patients were characterised correctly. In the latter group, high-grade gliomas were correctly identified in 27 of 28 cases by their amino acid uptake. It is concluded that the combination of ²⁰¹Tl and ¹²³I-IMT surpasses the accuracy of each single test in the differentiation of space-occupying lesions of the brain. Based on these preliminary results, a sequential strategy is proposed involving an initial ²⁰¹Tl SPET study and an additional ¹²³I-IMT SPET study in the event of positive ²⁰¹Tl uptake. Received 1 October 1999 and in revised form 8 January 2000     

Delineation of gliomas with magnetic resonance imaging using Gd-DTPA in comparison with computed tomography and positron emission tomography

Fourteen patients with cerebral gliomas were investigated by MR imaging using Gd-DTPA (Magnevist), CT with the contrast agent iohexol (Omnipaque) and, as a reference, positron emission tomography (PET) using 11C-L-methionine. Tumour areas with disruption of the blood-brain-barrier (BBB) as seen on MR and CT were compared with areas increased accumulation of methionine in PET. There were 6 patients with high-grade astrocytoma (grade III-IV), 5 with low-grade astrocytoma (grade I-II) and 3 with oligodendroglioma. In 4 high-grade tumours, PET showed a larger tumour or tumour tissue in additional areas, compared with enhancement on MR and CT, while in 2 cases the tumour extension was similar in the three modalities. In the low grade tumour group, the findings on PET differed from those on post-contrast MR or CT in 7 cases. In 3 of these cases, no disruption of the BBB was seen either on MR or on CT. In 2 of our 14 patients CT showed larger enhancement extension than MR and in 2 cases MR was superior to CT in this respect. The enhancement intensity was higher on MR in 4 patients and on CT in 2 patients. No definite difference in the delineation of tumour tissue between the T1 weighted SE sequences was found. The gradient echo sequences FLASH and FISP gave limited information that was less than that provided by the T1 weighted SE sequences. A greater increase in signal intensity in T1 weighted images was usually seen 5 min post-contrast in the high-grade tumours than in the low-grade ones.     

123I-IMP SPET in the diagnosis of primary central nervous system lymphoma

We reviewed N-isopropyl-p-[¹²³I]iodoamphetamine (¹²³I-IMP) single-photon emission tomography (SPET) images of brain tumours and assessed the usefulness of ¹²³I-IMP SPET for the diagnosis of primary central nervous system (CNS) lymphoma. We analysed 52 tumours that showed enhancement on magnetic resonance imaging: 11 malignant lymphomas, 3 anaplastic astrocytomas, 17 glioblastomas, 12 meningiomas, 4 metastatic brain tumours and 5 other brain tumours. ¹²³I-IMP uptake in the tumours on early (15-min) and delayed (4-h) scans was visually classified as high, moderate or low as compared with the contralateral brain cortex. Early and delayed ¹²³I-IMP uptake ratios comparing tumours with contralateral brain cortex (T/N ratio) were also calculated. In malignant lymphomas, the visual uptake of ¹²³I-IMP was moderate to high on the delayed scans. The delayed T/N ratios were significantly higher than the early ratios (P<0.05) and all lymphomas, with the exception of one small one, had delayed ratios greater than 0.9. In non-lymphomatous tumours, the visual uptake of ¹²³I-IMP was low on the delayed scans. The delayed T/N ratios were significantly lower than the early ratios (P<0.01) and all non-lymphomatous tumours had delayed ratios of less than 0.8. The T/N ratios of lymphomas were significantly higher than those of non-lymphomatous tumours on both early and delayed scans (P<0.0001). These results suggest that ¹²³I-IMP SPET may be a useful tool in the differential diagnosis of primary CNS lymphoma.     

Solitary brain lesions enhancing at MR imaging: evaluation with fluorine 18 fluorocholine PET

PURPOSE: To prospectively determine whether differences between benign and malignant brain lesions can be depicted with fluorine 18 ((18)F) fluorocholine positron emission tomography (PET). MATERIALS AND METHODS: Thirty consecutive patients (14 women, 16 men; age range, 26-79 years) with solitary brain lesions that were enhanced at magnetic resonance (MR) imaging underwent whole-brain (18)F-fluorocholine PET after giving informed consent in this institutional review board-approved, HIPAA-compliant study. Histopathologic diagnoses were made in 24 cases (13 high-grade gliomas, eight metastases to the brain, and three benign lesions). In six cases, benign lesions were diagnosed on the basis of longitudinal follow-up MR findings. The maximum standardized uptake value (SUV(max)) for lesion and peritumoral regions was measured on PET images, and a lesion-to-normal tissue uptake ratio (LNR) was calculated. Differences were assessed with one-way analysis of variance, Fisher exact, and Student t tests. RESULTS: Differences in SUV(max) between high-grade gliomas (1.89 +/- 0.78 [mean +/- standard deviation]), metastases (4.11 +/- 1.68), and benign lesions (0.59 +/- 0.31) were significant (P < .0001). LNRs also differed significantly (5.15 +/- 2.51, 10.91 +/- 2.14, and 1.28 +/- 0.32, respectively; P < .0001). These differences were also significant at pairwise analysis. The peritumoral LNR exceeded 2.0 in seven high-grade gliomas and no metastases (P = .02). In 14 radiation-treated patients, the lesions classified as benign demonstrated significantly less uptake compared with the recurrent tumors (SUV(max): 0.72 +/- 0.38 vs 2.27 +/- 1.24, P < .01; LNR: 1.36 +/- 0.43 vs 5.88 +/- 3.66, P < .01). CONCLUSION: High-grade gliomas, metastases, and benign lesions can be distinguished on the basis of measured fluorocholine uptake. Increased peritumoral fluorocholine uptake is a distinguishing characteristic of high-grade gliomas.     

Non-invasive grading of primary brain tumours: Results of a comparative study between SPET with123I-α-methyl tyrosine and PET with18F-deoxyglucose

Use of iodine-123--methyl tyrosine (¹²³I-IMT) allows investigation of the amino acid transport rate in gliomas. It was the aim of this study to compare the value of measurement of glucose metabolism with that of measurement of¹²³I-IMT uptake for the non-invasive grading of brain tumours. The study population comprised 23 patients with histopathologically proven primary brain tumours; 14 had high-grade gliomas, and nine low-grade brain neoplasms. Glucose metabolism was studied using an ECAT EXACT 47 positron emission tomography (PET) camera and fluorine-18 fluorodeoxyglucose (¹⁸F-FDG);¹²³I-IMT uptake was measured with the triple-headed single-photon emission tomography (SPET) camera, MULTISPECT 3.¹⁸F-FDG and¹²³I-IMT uptake was quantified as ratios between the uptake by the tumour and contralateral regions of reference. Glucose metabolism and amino acid uptake of the brain tumours correlated significantly (r=0.71,P <0.001). Assuming discrimination thresholds between high-grade and low-grade tumours of 0.8 for¹⁸F-FDG uptake and 1.8 for¹²³I-IMT uptake, the accuracy values of¹⁸F-FDG PET and¹²³I-IMT SPET for differentiating between high-grade and low-grade tumours were 21/23 (91%) and 19/23 (83%), respectively. The difference in diagnostic performance was not significant on receiver operating characteristic analysis (P >0.4). It is concluded that there is no major difference between the PET investigation of glucose metabolism and the less expensive SPET measurement of amino acid uptake in terms of their accuracy in evaluating the malignancy grade of primary brain tumours. This encourages the performance of further studies to analyse the potential impact of¹²³I-IMT SPET on the therapeutic management of patients with brain tumours.     

O-(2-[18F]fluorethyl)-L-tyrosine PET in the clinical evaluation of primary brain tumours

Purpose The aim of this study was to evaluate the differential uptake of O-(2-[¹⁸F]fluorethyl)-L-tyrosine (FET) in suspected primary brain tumours.Methods Positron emission tomography (PET) was performed in 44 patients referred for the evaluation of a suspected brain tumour. Acquisition consisted of four 10-min frames starting upon i.v. injection of FET. Tumour uptake was calculated as the ratio of maximal tumour intensity to mean activity within a reference region (FET_max).Results FET uptake above the cortical level was observed in 35/44 lesions. All histologically confirmed gliomas and many other lesions showed FET uptake to a variable extent. No uptake was observed in nine lesions (one inflammatory lesion, one dysembryoplastic neuroepithelial tumour, one mature teratoma, six lesions without histological confirmation). An analysis of uptake dynamics was done in the patients with increased FET uptake (22 gliomas, three lymphomas, three non-neoplastic lesions, three lesions with unknown histology and four other primaries). Upon classification of tumours into low (i.e. WHO I and II) and high grade (i.e. WHO III and IV), a significant difference in FET_max between the two categories was observed only in the first image frame (0–10 min p.i.), with FET_max=2.0 in low-grade and 3.2 in high-grade tumours (p<0.05); no significant differences were found in frame 4 (30–40 min p.i.), with FET_max=2.4 vs 2.7. Similar results were obtained when the analysis was applied only to astrocytic tumours (2.0 vs 3.1 in the first frame; 2.4 vs 2.6 in the fourth frame).Conclusion These initial results indicate that FET PET is a useful method to identify malignant brain lesions. It appears that high- and low-grade brain tumours exhibit a different uptake kinetics of FET. A kinetic analysis of FET PET may provide additional information in the differentiation of suspected brain lesions.     

High uptake of L-3-[123I]iodo-α-methyl tyrosine in pilocytic astrocytomas

Despite a favourable prognosis, pilocytic astrocytomas may exhibit signs of malignancy on various neuroimaging modalities. This retrospective analysis was conducted to determine whether scintigraphic features of malignancy are also found on single-photon emission tomography (SPET) using L-3-[¹²³I]iodo-!-methyl tyrosine (IMT) as a tracer. Twenty patients with pilocytic astrocytomas were retrospectively selected from a large series of patients referred for the evaluation of primary or recurrent brain tumours. IMT SPET was performed in 16 patients, positron emission tomography (PET) using 2-[¹⁸F]fluoro-2-deoxy-D-glucose (FDG) was available in 10 of the patients and SPET using technetium-99m tetrofosmin or thallium-201 had been performed in 11. Image analysis was performed using standard protocols to determine how many patients exceeded the respective thresholds of malignancy. Features of malignancy were found in 7/16 IMT SPET studies, in 7/10 FDG PET studies and in 7/11 of the residual SPET investigations. A significant correlation of tumour size and IMT uptake in primary pilocytic astrocytomas indicated partial volume effects to partly account for the differential uptake behaviour (n=10, r=0.87, P<0.05). Differences in IMT uptake in primaries (1.7ǂ.6, n=10) and in recurrent tumours (2.3ǂ.7, n=6) did not attain statistical significance. IMT SPET results indicative of malignancy are regularly found in pilocytic astrocytomas, despite their good prognosis. No uptake may be detected in largely cystic or in small tumours.     

Imaging in vivo herpes simplex virus thymidine kinase gene transfer to tumour-bearing rodents using positron emission tomography and [18F]FHPG

Radiolabelled ganciclovir analogues have shown promise as imaging agents to detect herpes simplex virus thymidine kinase (HSVtk) expression. This study evaluated the use of positron emission tomography (PET) imaging with 9-[(3-[¹⁸F]fluoro-1-hydroxy-2-propoxy)methyl]guanine ([¹⁸F]FHPG) to assess gene transfer into tumours. HSVtk-positive and HSVtk-negative cell lines were first treated in vitro with [¹⁸F]FHPG. To assess the efficacy of PET in detecting HSVtk expression following in vivo gene transfer, mice were injected intravenously with an adenovirus encoding HSVtk (Ad.HSVtk), a control vector (Ad.Bgl2) or saline. Subcutaneous human glioma xenografts were grown in mice and treated by direct injection of Ad.HSVtk or Ad.Bgl2. Imaging was performed 48 h after transduction. Similar experiments were performed using Fischer rats implanted with syngeneic tumours. The presence of the HSVtk protein was confirmed by immunohistochemistry. Biodistribution studies were also obtained in 14 naive mice. In vitro studies showed high and specific uptake of [¹⁸F]FHPG in HSVtk-positive cell lines, with an uptake ratio of up to 27:1. PET imaging and direct counting of major organs demonstrated HSVtk-specific tracer retention. In mice, HSVtk-positive tumours retained 3.4% dose/gram as compared to 0.6% for control tumours (P=0.03). They were clearly seen on the PET images as early as 100 min post injection. Similar results were obtained with syngeneic rat tumours. Biodistribution studies demonstrated the rapid distribution and clearance of the tracer in all major organs. Our results demonstrate that PET imaging of HSVtk gene transfer to tumours is feasible and is highly specific for HSVtk expression.     

Comparison of <Superscript>11</Superscript>C-choline PET and FDG PET for the differential diagnosis of malignant tumors

We prospectively assessed and compared the usefulness of ¹¹C-choline positron emission tomography (PET) with that of [¹⁸F]-2-fluoro-2-deoxy-d-glucose (FDG) PET for the differentiation between benign and malignant tumors. A total of 126 patients with 130 lesions were studied (25 brain tumors, 51 head and neck tumors, 15 bone tumors, 16 lung tumors, and 23 soft tissue tumors). ¹¹C-choline PET and FDG PET were performed from 5 and 40 min, respectively, after injection of 275–370 MBq tracer. PET data were evaluated using the standardized uptake value (SUV) and were analyzed in accordance with the pathologic data. The ¹¹C-choline uptake in malignancies was 3.9±2.3 (n=81), which was significantly higher than that in benign lesions (n=49) (2.6±1.7, P<0.005). The FDG uptake in malignancies was 5.9±3.8 (n=81) and was also significantly higher than that in benign lesions (2.8±2.0, P<0.0001). The ¹¹C-choline uptake in the lesions correlated with FDG uptake (r=0.65, P<0.003). According to an ROC analysis, the areas under the ROC curves (AUCs) for ¹¹C-choline PET were more than 0.8 in bone, head and neck, lung, and soft tissue tumors, while the AUC was 0.79 in brain tumors. The AUCs for FDG PET were similarly more than 0.8 in bone, head and neck, lung, and soft tissue tumors, but had a lower value of 0.585 in brain tumors. In brain, head and neck, bone, and soft tissue tumors, ¹¹C-choline showed higher contrast than FDG. In conclusion, it is feasible to use ¹¹C-choline PET for differentiation between malignant and benign tumours, especially of the brain, head and neck, bone, and soft tissue. However, attention needs to be drawn to the high uptake of ¹¹C-choline in some benign tumors and tumour-like lesions, as this will be of significance in clinical practice.     

Prospective study of p-[123I]iodo-L-phenylalanine and SPECT for the evaluation of newly diagnosed cerebral lesions: specific confirmation of glioma

Purpose

The differentiation between gliomas, metastases and gliotic or inflammatory lesions by imaging techniques remains a challenge. Gliomas frequently exhibit increased uptake of radiolabelled amino acids and are thus amenable to PET or SPECT imaging. Recently, p-[¹²³I]iodo-L-phenylalanine (IPA) was validated for the visualization of glioma by SPECT and received orphan drug status. Here we investigated its diagnostic performance for differentiating indeterminate brain lesions.

Methods

This prospective open study included 67 patients with newly diagnosed brain lesions suspicious for glioma (34 without and 33 with contrast enhancement in the MRI scan). Patients received 250 MBq IPA intravenously after overnight fasting. SPECT images at 30 min and 3 h post-injection were iteratively reconstructed and visually interpreted after image fusion with an MRI brain scan (fluid-attenuated inversion recovery sequence or T1-weighted contrast-enhanced image). Findings were correlated with results of stereotactic or open biopsies or serial imaging.

Results

Twenty-seven low-grade (2 WHO I, 25 WHO II) and 24 high-grade gliomas (1 WHO III, 23 WHO IV), 3 metastases originating from lung cancer as well as 13 non-neoplastic lesions were proven. All non-neoplastic lesions and all metastases were negative with IPA SPECT. Forty gliomas were true-positive (TP) and 11 false-negative (FN) findings (8 WHO II, 1 WHO III, 2 WHO IV) occurred. There were no false-positive (FP) findings. For the differentiation of primary brain tumours and non-neoplastic lesions, sensitivity and specificity were 78 and 100%. In 34 lesions without contrast enhancement in MRI, IPA SPECT resulted in 17 TP, 8 true-negative, 9 FN and no FP findings (sensitivity 65%, specificity 100%).

Conclusion

In patients with suspected glioma, IPA SPECT shows a high specificity, but especially in low-grade gliomas FN findings may occur. Due to the high positive predictive value a positive finding allows a suspected glioma to be confirmed.     

Imaging the serotonin transporter with positron emission tomography: initial human studies with [11C]DAPP and [11C]DASB

Two novel radioligands, N,N-dimethyl-2-(2-amino-4-methoxyphenylthio)benzylamine (DAPP) and (N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine (DASB), were radiolabeled with carbon-11 and evaluated as in vivo probes of the serotonin transporter (SERT) using positron emission tomography (PET). Both compounds are highly selective, with nanomolar affinity for the serotonin transporter and micromolar affinity for the dopamine and norepinephrine transporters. Six volunteers were imaged twice, once with each of the two radioligands. Both ligands displayed very good brain penetration and selective retention in regions rich in serotonin reuptake sites. Both had similar brain uptake and kinetics, but the cyano analogue, [¹¹C]DASB, had a slightly higher brain penetration in all subjects. Plasma analysis revealed that both radiotracers were rapidly metabolized to give mainly hydrophilic species as determined by reverse-phase high-performance liquid chromatography. Inhibition of specific binding to the SERT was demonstrated in three additional subjects imaged with [¹¹C]DASB following an oral dose of the selective serotonin reuptake blocker citalopram. These preliminary studies indicate that both these substituted phenylthiobenzylamines have highly suitable characteristics for probing the serotonin reuptake system with PET in humans.     

Biodistribution of [11C]methylaminoisobutyric acid, a tracer for PET studies on system A amino acid transport in vivo

[N-methyl-¹¹C]!-Methylaminoisobutyric acid (¹¹C-MeAIB) is a potentially useful tracer for positron emission tomography (PET) studies on hormonally regulated system A amino acid transport. ¹¹C-MeAIB is a metabolically stable amino acid analogue specific for system A amino acid transport. We evaluated the biodistribution of ¹¹C-MeAIB in rats and humans to estimate the usefulness of the tracer for in vivo human PET studies, for example, on regulation of system A amino acid transport and on tumour imaging. Healthy Sprague-Dawley rats (n=14) were killed 5, 20, 40 or 60 min after the injection of ¹¹C-MeAIB, and the tissue samples were weighed and counted for ¹¹C radioactivity. Ten lymphoma patients with relatively limited tumour burden underwent whole-body (WB) PET imaging with ¹¹C-MeAIB. In addition, three other patients had dynamic PET scanning of the head and neck area, and the tracer uptake was quantitated by calculating the kinetic influx constants (K_i values) for the tracer. In animal studies, the highest activity was detected in the kidney, pancreas, adrenal gland and intestines. In humans, the highest activity was found in the salivary glands, and after that in the kidney and pancreas, similar to the results in animal studies. Rapid uptake was also detected in the skeletal muscle. In the graphical analysis, linear plots were obtained, and the mean fractional tracer uptake values (K_i) of the parotid glands (n=3) and cervical muscles (n=3) were 0.039ǂ.008 min^-1 and 0.013ǂ.006 min^-1, respectively. The K_i value of the tumour (n=1) was 0.064 min^-1. Higher uptake of ¹¹C-MeAIB into the tumour tissue was encountered. These results encourage further ¹¹C-MeAIB PET studies in humans on the physiology and pathology of system A amino acid transport and on tumour detection.     

Prostate cancer: a comparative study of 11C-choline PET and MR imaging combined with proton MR spectroscopy

Purpose Prostate cancer is difficult to visualise in its early stages using current imaging technology. The present study aimed to clarify the utility of ¹¹C-choline PET for localising and evaluating cancer lesions in patients with prostate cancer by conducting a prospective comparison with magnetic resonance (MR) imaging combined with proton MR spectroscopy.Methods PET and MR imaging combined with proton MR spectroscopy were performed in 20 patients with prostate cancer. Correlations among the metabolite ratio of choline + creatine to citrate (Cho+Cr/Ci) on MR spectroscopy, serum PSA and maximum standardised uptake value (SUV_max) of ¹¹C-choline were assessed. The location of the primary lesion was assessed by the site of SUV_max and the laterality of the highest Cho+Cr/Ci ratio and confirmed by examination of surgical pathology specimens (n=16).Results PET exhibited a diagnostic sensitivity of 100% (20/20) for primary lesions, while the sensitivities of MR imaging and MR spectroscopy were 60% (12/20) and 65% (13/20), respectively. Weak linear correlations were observed between SUV_max and serum PSA (r=0.52, p<0.05), and between SUV_max and Cho+Cr/Ci ratio (r=0.49, p<0.05). Regarding the localisation of main primary lesions, PET results agreed with pathological findings in 13 patients (81%) (=0.59), while MR spectroscopy results were in accordance with pathological findings in eight patients (50%) (=0.11).Conclusion This preliminary study suggests that ¹¹C-choline PET may provide more accurate information regarding the localisation of main primary prostate cancer lesions than MR imaging/MR spectroscopy. A further clinical study of ¹¹C-choline PET in a large number of patients suspected of prostate cancer will be necessary to determine the clinical utility of ¹¹C-choline PET in patients who clinically require biopsy.     

Role of diffusion- and perfusion-weighted MR imaging for brain tumour characterisation

Purpose  This study was undertaken to correlate apparent diffusion coefficient (ADC) and relative regional cerebral blood volume (rrCBV) to histological findings in a large series of patients with primary or secondary brain tumours to evaluate diffusion-weighted (DWI) and perfusionweighted (PWI) imaging in the characterisation of cerebral tumors. Materials and methods  Ninety-eight patients with cerebral tumours, 46 of which were primary (seven grade 0-I, nine low-grade gliomas, two gliomatosis cerebri, nine lymphomas and 19 high-grade gliomas) and 52 secondary, underwent conventional magnetic resonance (MR) imaging completed with DWI and dynamic contrast susceptibility PWI. Both ADC and rrCBV were calculated on a workstation by using Functool 2 software. Student’s t test was used to determine any statistically significant differences in the ADC and rrCBV values. Results  Seventeen of 98 tumours were cystic or necrotic (12/17 hypointense and 5/17 hyperintense on DWI); the ADC value of hyperintense cystic areas was 0.97±0.23×10⁻³ mm²/s. The ADC value of solid tumours varied between 0.64 and 3.5×10⁻³ mm²/s. The rrCBV value was 1.4 (σ 0.66) in low-grade gliomas; 1.22 (σ 0.25) in lymphomas; 4.5 (σ 0.85) in grade III gliomas; 3.18 (σ 1.26) in grade IV gliomas and 2.53 (σ 1.6) in metastases. Conclusions  DWI has an important role in the differential diagnosis of cystic cerebral masses but not in tumour characterisation. PWI is helpful in differentiating high-from low-grade gliomas and lymphomas from high-grade gliomas.      

Dynamic study of supratentorial gliomas with L-methyl-11C-methionine and positron emission tomography

The regional kinetics of intravenously injected L-methyl-11C-methionine (11C-L-methionine) in the brain was investigated by positron emission tomography (PET) in 14 patients with gliomas. In both tumor and unaffected brain the tracer uptake reached a nearly constant level in 5 min or less. The ratio between the uptake of 11C-L-methionine by high-grade tumors and the uptake by unaffected brain was 1.9-4.8. In two cases of low-grade astrocytoma the ratio was 0.8-1.0. High uptakes of 11C-L-methionine occurred in gliomas even in the absence of blood-brain barrier defects as observed by other methods. This indicates that besides active transport of amino acid, a larger extracellular space in tumor as compared with unaffected brain tissue may also contribute to the increased uptake of 11C-L-methionine--derived radioactivity. In some patients delineation of the tumors was improved by use of PET with 11C-L-methionine as compared with computed tomography, angiography, and, in some instances, PET with 68Ga-EDTA. PET with 11C-L-methionine permits better evaluation of the tumor extent and may affect preoperative grading.