Comparison of 111In-DOTA-DPhe1-Tyr3-octreotide and 111In-DOTA-lanreotide scintigraphy and dosimetry in patients with neuroendocrine tumours

Purpose Somatostatin receptor scintigraphy with ¹¹¹In-DOTA-DPhe¹-Tyr³-octreotide (¹¹¹In-DOTA-TOC) and ¹¹¹In-DOTA-lanreotide (¹¹¹In-DOTA-LAN) has been used for staging of neuroendocrine tumours (NETs). However, the comparative diagnostic value of these radioligands on a lesion basis has not yet been established. The aim of this study was to compare the diagnostic capacity of ¹¹¹In-DOTA-TOC and ¹¹¹In-DOTA-LAN scintigraphy in patients with NETs, evaluating whether significant differences exist in lesion imaging with these radioligands. Furthermore, dosimetric data were compared. Methods Forty-five patients with NETs were investigated with ¹¹¹In-DOTA-TOC and ¹¹¹In-DOTA-LAN scintigraphy. Scintigraphic results were compared with those of conventional imaging and/or surgery in each patient, and also ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) in 20 patients. Results ¹¹¹In-DOTA-TOC and ¹¹¹In-DOTA-LAN scintigraphy were true positive in 42/45 (93%) and 39/45 (87%) patients, and imaged 74/91 (81%) and 73/91 (80%) tumour lesions, respectively. ¹¹¹In-DOTA-TOC and ¹¹¹In-DOTA-LAN detected liver metastases in 21 and 14 patients, mediastinal metastases in seven and 11 patients, and bone metastases in two and seven patients, respectively. These radioligands revealed lesions not seen by conventional imaging in seven and eight patients, respectively, or by ¹⁸F-FDG-PET in eight and seven patients, respectively. The estimated tumour absorbed doses for ⁹⁰Y-DOTA-TOC were higher than those for ⁹⁰Y-DOTA-LAN in 14 patients, whereas the opposite was true in 12 patients. Conclusion Both ¹¹¹In-DOTA-TOC and ¹¹¹In-DOTA-LAN are suitable for imaging tumour lesions in patients with NETs and can detect lesions that may not be seen by conventional imaging and ¹⁸F-FDG-PET. Compared with ¹¹¹In-DOTA-LAN, ¹¹¹In-DOTA-TOC has a superior diagnostic capacity for liver metastases, but a lower diagnostic capacity for metastatic lesions in mediastinum and bone.     

DOTATOC: A powerful new tool for receptor-mediated radionuclide therapy

This study presents the first successful use of a peptidic vector, DOTATOC, labelled with the -emitting radioisotope yttrium-90, for the treatment of a patient with somatostatin receptor-positive abdominal metastases of a neuroendocrine carcinoma of unknown localization. Tumour response and symptomatic relief were achieved. In addition, the new substance DOTA-TOC was labelled with the diagnostic chemical analogue indium-111 and studied in three patients with histopathologically verified neuroendocrine abdominal tumours for its diagnostic sensitivity and compared with the commercially available OctreoScan. In all patients the kidney-to-tumour uptake ratio (in counts per pixel) was on average 1.9-fold lower with¹¹¹In-DOTATOC than with OctreoScan. DOTATOC could be a potential new diagnostic and therapeutic agent in the management of neuroendocrine tumours.     

Selective hepatic arterial infusion of In-111-DTPA-Phe<Superscript>1</Superscript>-octreotide in neuroendocrine liver metastases

Purpose  The aim of this study is to evaluate the effectiveness of ¹¹¹In-DTPA-Phe¹-octreotide infusions after selective catheterization of the hepatic artery in inoperable metastasised liver, sst₂ receptor-positive neuroendocrine tumours due to the effect of ¹¹¹In Auger electron emission, minimising in parallel the toxicity of non-target tissue. Methods  The average dose per session administered monthly to each patient (17 cases in total) was 6.3 ± 2.3 GBq. Repetitions did not exceed 12-fold, except in one case (15 sessions). Response assessment was classified according to the Response Evaluating Criteria in Solid Tumours. CT/MRI scans were performed as baseline before, during and after the end of treatment, and monthly ultrasound images for follow-up measurements. Toxicity (World Health Organization criteria) was measured using blood and urine tests of renal, hepatic and bone marrow function. Results  Complete response was achieved in one (5.9%) patient and partial in eight (47.0%), and disease stabilization in 3 (17.7%) patients; five (29.4%) did not respond. A 32-month median survival time was estimated in 12 (70.5%). Nine of these 12 surviving had a mean target diameter shrinkage from 144 ± 81 to 60 ± 59 mm. Grade 1 erythro-, leuko- and thrombo-cytopenia occurred in three (17.6%) cases. Conclusion  In unresectable metastatic liver lesions positive for somatostatin receptors repeated, transhepatic high doses of ¹¹¹In-DTPA-Phe¹-octreotide show an effective therapeutic outcome. Given the locoregional modality character of the administration technique plus the extremely short range of ¹¹¹In Auger and internal conversion electrons emission, no nephro-, liver- or myelo-toxicity has so far been observed.     

In vitro and in vivo studies of three radiolabelled somatostatin analogues:123I-Octreotide (OCT),123I-Tyr-3-OCT and111In-TIRA-d-Phe-1-OCT

Scintigraphy with long-acting somatostatin (SST) analogues may be useful for the localization of tumours expressing receptors (R) for SST. In this study we have analysed the in vitro and in vivo binding properties of three SST analogues,¹²³I-octreotide (OCT),¹²³I-Tyr-3-OCT and¹¹¹In-DTPA-d-Phe-l-OCT. In vitro binding studies performed with a variety of primary tumours (n=48) as well as with several tumour cell lines (A431, HT29, PANC1, COLO320, HMC1, KU812) indicated significant in vitro binding of these three radiolabelled SST analogues to two subpopulations of SSTR, high (K _d 0.2–2.0 nM) and low (K _d 5–15 nM) affinity ones. The number of SSTR on tumour cells was at least a 1000-fold higher as compared with normal peripheral blood cells. Comparative scintigraphic studies using¹²³I-OCT and/or¹²³I-Tyr-3-OCT and/or¹¹¹In-DTPA-d-Phe-1-OCT were performed in 21 patients with histologically verified intestinal carcinoid tumours. Corresponding scintigraphic results were obtained in 18 of 21 patients investigated with two different SSTR ligands, either¹²³I-OCT/¹²³I-Tyr-3-OCT (four of five),¹²³I-OCT/¹¹¹In-DTPA-d-Phe-1-OCT (eight of nine), or¹²³I-Tyr-3-OCT/¹¹¹In-DTPA-d-Phe-1-OCT (six of seven). We conclude that various tumours express high amounts of SSTR which are recognized by three radiolabelled SST analogues:¹²³I-OCT,¹²³I-Tyr-3-OCT and¹¹¹In-DTPA-d-Phe-1-OCT. Differences between these SST analogues in their in vitro binding and/or in vivo scanning properties are observed in a minority of patients. Thus, the labelling of OCT with iodine may be an alternative approach for those nuclear medicine departments for which¹¹¹In-DTPA-d-Phe-1-OCT is not easily available, or is too expensive.     

Value of 111In-DOTA-lanreotide and 111In-DOTA-DPhe1-Tyr3-octreotide in differentiated thyroid cancer: results of in vitro binding studies and in vivo comparison with 18F-FDG PET

Purpose Radioiodine-negative thyroid cancer presents diagnostic and therapeutic difficulties, warranting the implementation of new imaging and treatment strategies. The purpose of this study was twofold. First, we investigated in vitro the binding characteristics of ¹¹¹In-DOTA-lanreotide (¹¹¹In-DOTA-LAN) and ¹¹¹In-DOTA-DPhe¹-Tyr³-octreotide (¹¹¹In-DOTA-TOC) to cells derived from differentiated thyroid cancer (DTC). Second, we evaluated the value of somatostatin receptor (SSTR) scintigraphy with these radioligands, as compared with ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET), for the detection of tumour lesions in DTC patients.Methods Binding of ¹¹¹In-DOTA-LAN and ¹¹¹In-DOTA-TOC to cells isolated from surgically removed thyroid tissue was evaluated in vitro by performing saturation and displacement studies. Eighteen DTC patients with elevated thyroglobulin (12 radioiodine-negative, six radioiodine-positive) were investigated with ¹¹¹In-DOTA-LAN, ¹¹¹In-DOTA-TOC and ¹⁸F-FDG PET scans.Results Large numbers of SSTR binding sites for ¹¹¹In-DOTA-LAN and ¹¹¹In-DOTA-TOC were found on the cells investigated. Both SSTR radioligands exhibited a high binding affinity for these SSTR binding sites. ¹¹¹In-DOTA-LAN and ¹¹¹In-DOTA-TOC scintigraphy detected 37 and 33 lesions, respectively, in 17 (94%) patients each, whereas ¹⁸F-FDG PET revealed 30 lesions in 15 (83%) patients. Uptake of both SSTR radioligands was found in several radioiodine-negative sites. No striking differences in lesion imaging by ¹¹¹In-DOTA-LAN and ¹¹¹In-DOTA-TOC were found. In both radioiodine-negative and radioiodine-positive patients, more lesions were SSTR-positive/¹⁸F-FDG-negative than were ¹⁸F-FDG-positive/SSTR-negative.Conclusion Adding a SSTR scan with these radioligands to the diagnostic work-up increases the diagnostic capacity in DTC, and should be considered particularly in radioiodine-negative patients with elevated thyroglobulin levels.These studies were supported in part by the Austrian National Bank (Anniversary Foundation, Projects No. 7487 and 8185) and by a Foundation of the Mayor of the City of Vienna.     

Yttrium-90 and indium-111 labelling, receptor binding and biodistribution of [DOTA0,d-Phe1,Tyr3]octreotide, a promising somatostatin analogue for radionuclide therapy

In vitro octreotide receptor binding of [¹¹¹In-DOTA⁰,d-Phe¹,Tyr³]octreotide (¹¹¹In-DOTATOC) and the in vivo metabolism of⁹⁰Y or¹¹¹In-labelled DOTATOC were investigated in rats in comparison with [¹¹¹In-DTPA⁰]octreotide [¹¹¹In-DTPAOC).¹¹¹In-DOTATOC was found to have an affinity similar to octreotide itself for the octreotide receptor in rat cerebral cortex microsomes. Twenty-four hours after injection of⁹⁰Y or¹¹¹In-labelled DOTATOC, uptake of radioactivity in the octreotide receptor-expressing tissues pancreas, pituitary, adrenals and tumour was a factor of 2–6 that after injection of¹¹¹In-DTPAOC. Uptake of labelled DOTATOC in pituitary, pancreas, adrenals and tumour was almost completely blocked by pretreatment with 0.5 mg unlabelled octreotide, indicating specific binding to the octreotide receptors. These findings strongly indicate that⁹⁰Y-DOTATOC is a promising radiopharmaceutical for radiotherapy and that¹¹¹In-DOTATOC is of potential value for diagnosis of patients with octreotide receptor-positive lesions, such as most neuroendocrine tumours.     

Pre-therapeutic dosimetry and biodistribution of 86Y-DOTA-Phe1-Tyr3-octreotide versus 111In-pentetreotide in patients with advanced neuroendocrine tumours

Purpose For the internal radiotherapy of neuroendocrine tumours, the somatostatin analogue DOTATOC labelled with ⁹⁰Y is frequently used [⁹⁰Y-DOTA-Phe¹-Tyr³-octreotide (SMT487-OctreoTher)]. Radiation exposure to the kidneys is critical in this therapy as it may result in renal failure. The aim of this study was to compare cumulative organ and tumour doses based upon dosimetric data acquired with the chemically identical ⁸⁶Y-DOTA-Phe¹-Tyr³-octreotide (considered as the gold standard) and the commercially available ¹¹¹In-pentetreotide.Methods The cumulative organ and tumour doses for the therapeutic administration of 13.32 GBq ⁹⁰Y-DOTA-Phe¹-Tyr³-octreotide (three cycles, each of 4.44 GBq) were estimated based on the MIRD concept (MIRDOSE 3.1 and IMEDOSE). Patients with a cumulative kidney dose exceeding 27 Gy had to be excluded from subsequent therapy with ⁹⁰Y-DOTA-Phe¹-Tyr³-octreotide, in accordance with the directives of the German radiation protection authorities.Results The range of doses (mGy/MBq ⁹⁰Y-DOTA-Phe¹-Tyr³-octreotide) for kidneys, spleen, liver and tumour masses was 0.6–2.8, 1.5–4.2, 0.3–1.3 and 2.1–29.5 (⁸⁶Y-DOTA-Phe¹-Tyr³-octreotide), respectively, versus 1.3–3.0, 1.8–4.4, 0.2–0.8 and 1.4–19.7 (¹¹¹In-pentetreotide), with wide inter-subject variability. Despite renal protection with amino acid infusions, estimated cumulative kidney doses in two patients exceeded 27 Gy.Conclusion Compared with ⁸⁶Y-DOTA-Phe¹-Tyr³-octreotide, dosimetry with ¹¹¹In-pentetreotide overestimated doses to kidneys and spleen, whereas the radiation dose to the tumour-free liver was underestimated. However, both dosimetric approaches detected the two patients with an exceptionally high radiation burden to the kidneys that carried a potential risk of renal failure following radionuclide therapy.     

The Bücherer-Strecker synthesis of d- and l-(1-11C)tyrosine and the in vivo study of l-(1-11C)tyrosine in human brain using positron emission tomography

The synthesis of d-and l-(1-¹¹C)tyrosine, starting with ¹¹C-cyanide, is reported. dl-(1-¹¹C)Tyrosine was prepared by the Bücherer-Strecker reaction, from carrier added ¹¹C-cyanide with an incorporation of 80% in 20 min. The isolation of the pure d- and l-amino acid isomers from the enantiomeric mixture was accomplished within 15 min by preparative HPLC using a chiral stationary phase and a phosphate buffer as the mobile phase. Typically, the total synthesis time was 50 min (including purification) from end of trapping of ¹¹C-cyanide, with a radiochemical yield of d- and l-amino acid of 40%–60%. The d- and l-(1-¹¹C)tyrosine were both obtained optically pure, with a carrier added specific activity of 0.3–0.5 Ci/mmol and a radiochemical purity better than 99%. The ¹¹C labelled l-tyrosine was used in an in vivo study in the human brain using positron emission tomography (PET).     

FDG-PET imaging in HIV-infected subjects: relation with therapy and immunovirological variables

Purpose

To characterise tissue sites of immune activation and HIV replication we performed FDG-PET in ART-treated and ART-naive HIV-infected individuals. Specific aims were to establish whether HIV-infected patients can be differentiated on the basis of the detection of specific locations of viral replication, even in the presence of an apparently optimal immunovirological response to ART, and whether these FDG-PET findings can be related to immunovirological variables and AIDS history status.

Patients and methods

Patients were divided into five groups as follows: subgroup A1 (full responders, n?=?8): current ART treatment, CD4+ T lymphocytes >500/mL, viral load <50 copies/mL; subgroup A2 (full responders, n?=?5): same criteria as A-1, but with a previous history of AIDS; subgroup A3 (immunological non responders, n?=?5): current ART treatment, viral load <50 copies/mL, low CD4+ T lymphocytes (<200/mL); group B (virological non responders, n?=?2): current ART treatment, CD4+ T lymphocytes around 500/mL, viral load >50,000 copies/mL; group C (ART-naïve, n?=?5): no current or previous ART treatment, increased viral load.

Results

PET images revealed different patterns of FDG uptake. All ART-treated patients with either suppressed (<50 copies/mL; Group A) or high viremia (group B) showed a normal pattern of FDG uptake. On the contrary, the ART-naïve subjects with high viraemia (group C) displayed multiple foci of increased glucose metabolism in the lymph nodes. In the ART-naïve subjects, FDG uptake, apparently related to viraemia level, was observed in the upper torso mainly in the axillary nodes bilaterally in patients with viraemia below 100,000 copies/mL; in those with viraemia higher than 100,000 copies/mL, FDG uptake was also observed in the inguinal lymph nodes.

Conclusions

The emergence, in our study, of a correlation between the percentage of CD8+/CD38+/RO+ T cells (well established markers of progression to AIDS independently of CD4+ T lymphocytes) and positive FDG-PET in ART-naive patients is a novel finding that seems to confer prognostic value on FDG uptake. FDG uptake is strongly associated with response to ART independently of a previous AIDS diagnosis. Notably, no differences were observed between ART-treated subjects classed as immunological responders and those classed as non responders. Data herewith indicate that FDG uptake and immunological variables are unrelated when ART is being administered. This is evidence of the complementarity of immunological and FDG measures. FDG uptake is a sensitive marker of disease state and its relation with CD8+/CD38+/CD45RO+ T cells indicates that it can be considered a marker of disease status. The lack of a correlation between FDG uptake and immunological variables in patients under ART warrants further investigation.

     

Increased accuracy of the carbon-14d-xylose breath test in detecting small-intestinal bacterial overgrowth by correction with the gastric emptying rate

To date, there is no general agreement as to which test is to be preferred for the diagnosis of small-intestinal bacterial overgrowth. The 1-g carbon-14d-xylose breath test has been proposed as a very sensitive and specific test for the diagnosis of bacterial overgrowth. However, in patients with severe gastrointestinal motor dysfunction, the lack of consistent delivery of¹⁴C-d-xylose to the region of bacterial contamination may result in a negative result. The aim of this study was to determine whether the accuracy of¹⁴C-d-xylose breath test for detecting bacterial overgrowth can be increased by correction with the gastric emptying rate of¹⁴C-d-xylose. Ten culture-positive patients and ten culture-negative controls were included in the study. Small-intestinal aspirates for bacteriological culture were obtained endoscopically. A liquid-phase gastric emptying study was performed simultaneously to assess the amount of¹⁴C-d-xylose that entered the small intestine. The results of the percentage of expired¹⁴CO₂ at 30 min were corrected with the amount of¹⁴C-d-xylose that entered the small intestine. There were six patients in the culture-positive group with a¹⁴CO₂ concentration above the normal limit. Three out of four patients with initially negative results using the uncorrected method proved to be positive after correction. All these three patients had prolonged gastric emptying of¹⁴C-d-xylose. When compared with cultures of small-intestine aspirates, the sensitivity and specificity of the uncorrected¹⁴C-d-xylose breath test were 60% and 90%, respectively. In contrast, the sensitivity and specificity of the corrected¹⁴C-d-xylose breath test improved to 90% and 100%, respectively. In conclusion, using the gastric emptying rate of¹⁴C-d-xylose as a correcting factor, we found a higher sensitivity and specificity for the¹⁴C-d-xylose breath test in the detection of small-intestinal bacterial overgrowth than were achieved with the conventional method.     

Concordance between results of somatostatin receptor scintigraphy with <Superscript>111</Superscript>In-DOTA-DPhe<Superscript>1</Superscript>-Tyr<Superscript>3</Superscript>-octreotide and chromogranin A assay in patients with neuroendocrine tumours

Purpose  Somatostatin receptor scintigraphy (SRS) and chromogranin A (CgA) assay have successfully been implemented in the clinical work-up and management of neuroendocrine tumour (NET) patients. However, there is still a lack of studies comparing results in these patients. Our aim was to compare directly in NET patients SRS and CgA assay results with special regard to tumour features such as grade of malignancy, primary origin, disease extent and function. Methods  One hundred twenty consecutive patients with histological confirmed NETs were investigated with ¹¹¹In-DOTA-DPhe¹-Tyr³-octreotide (¹¹¹In-DOTA-TOC) SRS and CgA immunoradiometric assay. Tumours were classified by cell characteristics [well-differentiated NETs, well-differentiated neuroendocrine carcinomas, poorly differentiated neuroendocrine carcinomas (PDNECs)], primary origin (foregut, midgut, hindgut, undetermined), disease extent (limited disease, metastases, primary tumour and metastases) and functionality (secretory, nonsecretory). Results  SRS was positive in 107 (89%) patients; CgA levels were increased in 95 (79%) patients. Overall, concordance between SRS and CgA results was found in 84 patients. Positive SRS but normal CgA level were found in 24 patients, with higher prevalence (p < 0.05) in patients with nonsecretory tumours. Conversely, negative SRS but CgA level increased were seen in 12 patients, with higher proportion (p < 0.05) in patients with PDNECs and tumours of hindgut origin. Conclusions  Overall, ¹¹¹In-DOTA-TOC SRS proved to be more sensitive than CgA in NETs patients. Tumour differentiation, disease extent and presence of liver metastases impact both SRS and CgA results, whereas nonsecretory activity is a negative predictor of only CgA increase. PDNECs and hindgut origin of tumours predispose to discrepancies with negative SRS but increased CgA levels.     

Preliminary results for positron emission mammography: real-time functional breast imaging in a conventional mammography gantry

In order to optimally integrate radiotracer breast imaging within the breast clinic, anatomy and pathology should be easily correlated with functional nuclear medicine breast images. As a first step in the development of a hybrid functional/anatomic breast imaging platform with biopsy capability, a conventional X-ray mammography gantry was modified to image the compressed breast with positron emitters. Phantom studies with the positron emission mammography (PEM) device showed that a 1-cc hot spot could be detected within 5 min. A preliminary clinical trial demonstrated in vivo visualization of primary breast cancer within 4 min. For sites where positron-emitting radionuclides are available, PEM promises to achieve low-cost directed functional examination of breast abnormalities, with the potential for achieving X-ray correlation and image-guided biopsy.     

Uptake kinetics and biodistribution of <Superscript>14</Superscript>C-<Emphasis Type="SmallCaps">d</Emphasis>-luciferin—a radiolabeled substrate for the firefly luciferase catalyzed bioluminescence reaction: impact on bioluminescence based reporter gene imaging

Purpose  Firefly luciferase catalyzes the oxidative decarboxylation of d-luciferin to oxyluciferin in the presence of cofactors, producing bioluminescence. This reaction is used in optical bioluminescence-based molecular imaging approaches to detect the expression of the firefly luciferase reporter gene. Biokinetics and distribution of the substrate most likely have a significant impact on levels of light signal and therefore need to be investigated. Methods  Benzene ring ¹⁴C(U)-labeled d-luciferin was utilized. Cell uptake and efflux assays, murine biodistribution, autoradiography and CCD-camera based optical bioluminescence imaging were carried out to examine the in vitro and in vivo characteristics of the tracer in cell culture and in living mice respectively. Results  Radiolabeled and unlabeled d-luciferin revealed comparable levels of light emission when incubated with equivalent amounts of the firefly luciferase enzyme. Cell uptake assays in pCMV-luciferase-transfected cells showed slow trapping of the tracer and relatively low uptake values (up to 22.9-fold higher in firefly luciferase gene-transfected vs. nontransfected cells, p = 0.0002). Biodistribution studies in living mice after tail-vein injection of ¹⁴C-d-luciferin demonstrated inhomogeneous tracer distribution with early predominant high radioactivity levels in kidneys (10.6% injected dose [ID]/g) and liver (11.9% ID/g), followed at later time points by the bladder (up to 81.3% ID/g) and small intestine (6.5% ID/g), reflecting the elimination routes of the tracer. Kinetics and uptake levels profoundly differed when using alternate injection routes (intravenous versus intraperitoneal). No clear trapping of ¹⁴C-d-luciferin in firefly luciferase-expressing tissues could be observed in vivo. Conclusions  The data obtained with ¹⁴C-d-luciferin provide insights into the dynamics of d-luciferin cell uptake, intracellular accumulation, and efflux. Results of the biodistribution and autoradiographic studies should be useful for optimizing and adapting optical imaging protocols to specific experimental settings when utilizing the firefly luciferase and d-luciferin system. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Diagnosis of maxillofacial tumor withl-3-[18F]-fluoro-α-methyltyrosine (FMT) PET: a comparative study with FDG-PET

OBJECTIVES: To compare L-3-[18F]-fluoro-a-methyltyrosine (FMT)-positron emission tomography (PET) and 2-[18F]-fluoro-2-deoxy-D-glucose (FDG)-PET in the differential diagnosis of maxillofacial tumors. METHODS: This study included 36 patients (16 males, 20 females; 31-90 years old) with untreated malignant tumors (34 squamous cell carcinoma, one mucoepidermoid carcinoma, one rhabdomyosarcoma) and seven patients (five males, two females; 32-81 years old) with benign lesions. In all patients, both FMT-PET and FDG-PET were performed within two weeks before biopsy or treatment of the lesions. To evaluate the diagnostic usefulness of FMT-PET and FDG-PET, visual interpretation and semiquantitative analysis were performed. PET images were rated according to the contrast of tumor uptake as compared with background, and were statistically analyzed. As a semiquantitative analysis, standardized uptake values (SUV) of the primary tumors were measured, and the SUV data were analyzed using receiver operating characteristic (ROC) curves. Results: The mean SUV of the malignant lesions were significantly higher than those of the benign lesions in both FMT-PET (2.62 +/- 1.58 vs. 1.20 +/- 0.30, p < 0.01) and FDG-PET (9.17 +/- 5.06 vs. 3.14 +/- 1.34, p < 0.01). A positive correlation (r = 0.567, p < 0.0001, n = 46) was noted between FMT and FDG. ROC analysis revealed that there was no statistically significant difference in SUVs between FMT and FDG for differentiating malignant tumors. In 27 of 36 patients, FMT-PET had better contrast of malignant tumor visualization to the surrounding normal structures by visual assessment (p < 0.005, binomial proportion test). CONCLUSIONS: Differential diagnosis of FMT-PET based on the uptake in maxillofacial tumors is equivalent to FDG-PET. However, the contrast of FMT uptake between maxillofacial tumors and the surrounding normal structures is higher than that of FDG, indicating the possibility of accurate diagnosis of maxillofacial tumors by FMT-PET.     

Crossed cerebellar diaschisis: a positron emission tomography study withl-[methyl-11C]methionine and 2-deoxy-2-[18F]fluoro-d-glucose

OBJECTIVE: Crossed cerebellar diaschisis (CCD) is defined as a depression of blood flow and oxidative metabolism of glucose in the cerebellum contralateral to a supratentorial brain lesion, as detected with positron emission tomography (PET) and single photon emission computed tomography. We examined whether L-[methyl-11C]methionine (MET) uptake is affected in CCD. METHODS: In 12 patients with a unilateral supratentorial brain tumor, we evaluated the uptake of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) and MET in the cerebellar hemispheres by means of PET. Asymmetry index (AI) was defined as a difference in the average count between the ipsilateral and contralateral cerebellar hemispheres divided by the average count in both cerebellar hemispheres. Patients with AI of FDG PET more than 0.1 and those with AI equal to 0.1 or less than 0.1 were classified as CCD-positive and CCD-negative, respectively. RESULTS: Six patients were CCD-positive and others were CCD-negative in the FDG PET study. Between CCD-positive and CCD-negative patients, mean AI of MET was not significantly different (0.017 +/- 0.023 and 0.014 +/- 0.039, respectively). CONCLUSIONS: Different from glucose metabolism, cerebellar MET uptake was not affected in CCD. The present study may indicate that cerebellar MET uptake is independent of suppression of cerebellar neuronal activity.     

First experience in healthy volunteers with technetium-99m l,l-ethylenedicysteine,a new renal imaging agent

Animal studies have indicated that technetium-99m l,l-ethylenedicysteine (^99mTc-l,l-EC) may be a promising tracer agent for renal function studies. We have performed a paired study with ^99mTc-mercaptoacetyltriglycine (^99mTc-MAG₃) and ^99mTc-l,l-EC in six male volunteers. In both cases, iodine-131-labelled o-iodohippurate was co-injected as an internal biological standard. The analog images between 0 and 30 min p.i. were of identical diagnostic value for both tracer agents. The two renograms were similar in all volunteers. The mean 1-h plasma clearance for ^99mTc-MAG₃ and 99 mTc-l,l-EC was significantly different, respectively 382.9 ± 17.1 ml/min per 1.73 m² versus 460.2 ± 47.7 ml/min per 1.73 m² (P<0.003). The urinary excretion after 30 min p.i. was 69.4% ± 5.6% of the injected dose for ^99mTc-MAG₃ versus 66.5% ± 2.5% for ^99mTc-l,l-EC (P>0.05) and after 60 min p.i. respectively 83.1% ± 3.9% versus 79.8 % ± 4.3 % (P > 0.05). ^99mTc-l,l-EC has a very low plasma protein binding (31% ± 6.8%) as compared to ^99mTc-MAG₃ (88% ± 5.2%) and a larger volume of distribution. Although the exact mechanism responsible for the high plasma clearance of ^99mTc-l,l-EC is not yet fully known, we conclude that this new agent merits further clinical evaluation in patients to establish its value as a renal radiopharmaceutical. Correspondence to: A. Verbruggen     

Simplified enzymatic synthesis and biodistribution of 11C-S-adenosyl-l-methionine

¹¹C-S-Adenosyl-l-methionine (¹¹C-SAM) was synthesized enzymatically from ¹¹C-l-methionine using ratliver extract [40%–50% saturated (NH₄)₂SO₄ fraction] as the enzyme source. In biodistribution studies in rats, the highest uptake of ¹¹C-SAM was found in the kidneys. ¹¹C-SAM was also accumulated in the small intestine, pancreas, adrenal gland, liver, and spleen. The uptake of ¹¹C-SAM in the brain increased with time, but remained low. At 30 min after injection, about 50%–60% of the ¹¹C radioactivity was present in the acid-insoluble fraction of the kidneys and liver. When a high loading dose of ¹¹C-SAM was administered, the kidney uptake was enhanced, but the proportion of the radioactivity present in the acid-insoluble fraction was lower. In a study of one rabbit, the kidney uptake was of ¹¹-SAM clearly visualized using positronemission tomography.     

PET imaging of brain astrocytoma with 1-11C-acetate

Purpose The purpose of this study was to assess the use of 1-¹¹C-acetate (ACE) as a metabolic tracer for the detection and characterisation of astrocytomas. Methods Positron emission tomography (PET) studies with ACE and 2-¹⁸F-fluoro-2-deoxy-D-glucose (FDG) were performed sequentially in 26 patients with primary astrocytomas. Images were analysed by visual interpretation and determination of the tumour to cortex ratio (T/C ratio) and standardised uptake value (SUV). The tumour uptake was visually scored into three grades as compared with the contralateral cortex: clearly lower (–), almost equal (+) and clearly higher (++). Results There were 85% of astrocytomas with ++ ACE uptake, 15% with + ACE uptake and none with – ACE uptake. Only 19% of astrocytomas had ++ FDG uptake. Thirty-seven percent of high-grade astrocytomas had + FDG uptake and 37% had – FDG uptake. The sensitivity and specificity of the FDG T/C ratio in discriminating high-grade from low-grade astrocytomas were 79% and 100%, respectively, at the cutoff value of 0.75. Using 2.33 as the cutoff value of the ACE T/C ratio, the sensitivity and specificity were 42% and 86%, respectively. FDG was better than ACE in discriminating high-grade from low-grade astrocytomas. T/C ratios and SUVs of FDG uptake of tumours correlated with the histological grades, but those of ACE uptake did not. Conclusion ACE appears to be a promising tracer for use in the detection of primary astrocytomas, but is of limited value in the differentiation of high- and low-grade astrocytomas. ACE is complementary to FDG for the diagnosis and characterisation of astrocytoma.     

Distant metastases and synchronous second primary tumors in patients with newly diagnosed oropharyngeal and hypopharyngeal carcinomas: evaluation of <Superscript>18</Superscript>F-FDG PET and extended-field multi-detector row CT

Introduction  Patients with oropharyngeal or hypopharyngeal squamous cell carcinoma (SCC) have a high risk of having distant metastases or second primary tumors. We prospectively evaluate the clinical usefulness of ¹⁸F-fluoro-2-deoxyglucose positron emission tomography (¹⁸F-FDG PET), extended-field multi-detector computed tomography (MDCT), and their side-by-side visual correlation for the detection of distant malignancies in these two tumors at presentation. Materials and methods  A total of 160 patients with SCC of the oropharynx (n = 74) or hypopharynx (n = 86) underwent ¹⁸F-FDG PET and extended-field MDCT to detect distant metastases or second primary tumors. Suspected lesions were investigated by means of biopsy, clinical, or imaging follow-up. Results  Twenty-six (16.3%) of our 160 patients were found to have distant malignancy. Diagnostic yields of ¹⁸F-FDG PET and MDCT were 12.5% and 8.1%, respectively. The sensitivity of ¹⁸F-FDG PET for detection of distant malignancies was 1.5-fold higher than that of MDCT (76.9% vs. 50.0%, P = 0.039), while its specificity was slightly lower (94.0% vs. 97.8%, P = 0.125). Side-by-side visual correlation of MDCT and ¹⁸F-FDG PET improved the sensitivity and specificity up to 80.8% and 98.5%, respectively, leading to alteration of treatment in 13.1% of patients. A significant difference in survival rates between its positive and negative results was observed. Conclusion   ¹⁸F-FDG PET and extended-field MDCT had acceptable diagnostic yields for detection of distant malignancies in untreated oropharyngeal and hypopharyngeal SCC. ¹⁸F-FDG PET was 1.5-fold more sensitive than MDCT, but had more false-positive findings. Their visual correlation improved the diagnostic accuracy, treatment planning, and prognosis prediction.     

The added value of [<Superscript>18</Superscript>F]fluoro-<Emphasis Type="SmallCaps">L</Emphasis>-DOPA PET in the diagnosis of hyperinsulinism of infancy: a retrospective study involving 49 children

Purpose Neuroendocrine diseases are a heterogeneous group of entities with the ability to take up amine precursors, such as L-DOPA, and convert them into biogenic amines, such as dopamine. Congenital hyperinsulinism of infancy (HI) is a neuroendocrine disease secondary to either focal adenomatous hyperplasia or a diffuse abnormal pancreatic insulin secretion. While focal hyperinsulinism may be reversed by selective surgical resection, diffuse forms require near-total pancreatectomy when resistant to medical treatment. Here, we report the diagnostic value of PET with [¹⁸F]fluoro-L-DOPA in distinguishing focal from diffuse HI. Methods Forty-nine children were studied with [¹⁸F]fluoro-L-DOPA. A thoraco-abdominal scan was acquired 45–65 min after the injection of 4.2 ± 1.0 MBq/kg of [¹⁸F]fluoro-L-DOPA. Additionally, 12 of the 49 children were submitted to pancreatic venous catheterisation for blood samples (PVS) and 31 were also investigated using MRI. Results We identified abnormal focal pancreatic uptake of [¹⁸F]fluoro-L-DOPA in 15 children, whereas diffuse radiotracer uptake was observed in the pancreatic area in the other 34 patients. In children studied with both PET and PVS, the results were concordant in 11/12 cases. All patients with focal radiotracer uptake and nine of the patients with diffuse pancreatic radiotracer accumulation, unresponsive to medical treatment, were submitted to surgery. In 21 of these 24 patients, the histopathological results confirmed the PET findings. In focal forms, selective surgery was followed by clinical remission without carbohydrate intolerance. Conclusion These data demonstrate that PET with [¹⁸F]fluoro-L-DOPA is an accurate non-invasive technique allowing differential diagnosis between focal and diffuse forms of HI.