Radiolabeling approaches for cholecystokinin B receptor imaging.

Regulatory peptides and their analogs are being extensively investigated as radiopharmaceuticals for cancer imaging. In particular, cholecystokinin (CCK) receptors of the subtype B (CCK-BR) have been shown to be overexpressed in certain neuroendocrine tumors including medullary thyroid cancer. Our recent work has focused on new methods to radiolabel the CCK8 peptide with (111)In or (99m)Tc for the purpose of developing radiopharmaceuticals for in vivo CCK-B receptor imaging. Labeling of CCK8 with (111)In was achieved at the N-terminus of the peptide by adding, in solid phase, a glutamate coupled diethylenetriaminepentaacetic acid (DTPA) moiety through a glycine linker, yielding DTPA-Glu-G-CCK8. For labeling with (99m)Tc, the CCK8 peptide was modified at its N-terminus by introducing, in the following order--cysteine, glycine, and a diphenylphosphinopropionyl moiety--giving a 10-residue peptide derivative, Phos-GC-CCK8. A cell culture model was developed for the purpose of evaluating the binding properties of these two ligands. The human epidermoid carcinoma cell line, A431, was transfected with a plasmid containing the full coding sequence of the human CCK-BR under a strong viral promoter, obtaining a number of receptors in the range of 2-5 x 10(6) per cell. Control cells were transfected with vector alone. An animal tumor model utilizing these two cell lines was developed to evaluate the specificity of interaction with the CCK-BR and biodistribution properties of the compounds. CCK-BR positive and control cells were subcutaneously injected in opposite flanks of CD1 female nude mice in order to obtain xenografts differing only in their ability to express CCK-B receptors. High performance liquid chromatography (HPLC) and other chromatographic methods were utilized to assess stability of the radiolabeled compounds after injection. Both (111)In-DTPA-Glu-G-CCK8 and (99m)Tc-Phos-GC-CCK8 showed similar binding affinities for cultured CCK-BR expressing cells, with dissociation constants in the range of 20-40 nM. With the two xenograft approach, we were able to demonstrate specific interaction with the receptor of both CCK analogs in our animal model. The data obtained shows rapid specific localization of both compounds on the CCK-BR overexpressing xenografts. Both tracers show rapid plasma clearance of unbound peptide. Clearance of (111)In-DTPA-Glu-G-CCK8 appears to be preferentially through the kidneys, whereas (99m)Tc-Phos-GC-CCK8 clearance occurs both through kidneys and the hepatobiliary system. Both our labeling approaches appear adequate for clinical use of peptide based radiopharmaceuticals, although (99m)Tc-Phos-GC-CCK8 shows elevated accumulation in the gastrointestinal tract, which causes high background activity.

Imaging of adrenal tumors using FDG PET: comparison of benign and malignant lesions.

OBJECTIVE: The aim of this study was to differentiate benign from malignant adrenal tumors using positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in patients with unilateral adrenal masses originally detected by CT or MR imaging. CONCLUSION: PET imaging with FDG can metabolically characterize adrenal masses. Abnormally increased FDG uptake in adrenal malignancies allows one to differentiate these abnormalities from benign lesions. Whole-body PET can also reveal extraadrenal tumor sites in patients with malignant tumors, using a single imaging technique for accurate disease staging.

Tc-99m MIBI scintigraphy in patients with lung cancer. Comparison with CT and fluorine-18 FDG PET imaging.

Tc-99m MIBI imaging has been used to evaluate patients with different neoplastic disorders, but its role in nuclear oncology has not been definitely established. In this study, we compared the results of Tc-99m MIBI (planar and SPECT imaging) with those of F-18 FDG PET radionuclide studies in 19 patients who had proven lung cancer. One patient was studied in follow-up. All patients underwent chest CT scans. MIBI and FDG images were qualitatively and quantitatively analyzed using region of interest analysis. Quantitative evaluation of MIBI and FDG activities in lung-tumor lesions was performed calculating tumor/nontumor ratios. On CT, 18 lung tumors were detected, while one patient was disease free. For lung lesions, the diagnostic sensitivity of planar MIBI imaging was 83%, while those of MIBI SPECT and FDG PET were both 100%. The quantitative analysis of lung-tumor MIBI and FDG activities showed that FDG uptake was significantly (P < 0.001) higher compared with MIBI uptake (5.5 +/- 3.1 vs 2.1 +/- 0.6); concordant MIBI and FDG images were found in 4 lesions in terms of central activity defect showing central necrotic tumor tissue. For lymph node abnormalities, planar MIBI scan only detected 3 lesions in 3 patients, whereas MIBI SPECT identified 9 lesions in 5 patients. FDG PET showed 13 lymph node abnormalities in 5 patients. This study shows similar results of Tc-99m MIBI SPECT and F-18 FDG PET in the diagnostic evaluation of patients with lung tumors. However, FDG lung tumor uptake was significantly higher compared with MIBI accumulation, suggesting a high glucose tumor metabolism. Thus, MIBI SPECT imaging may be useful to evaluate such patients and may be considered an alternative when PET is not available.

Unsupervised, automated segmentation of the normal brain using a multispectral relaxometric magnetic resonance approach.

The purpose of this study was the development and testing of a method for unsupervised, automated brain segmentation. Two spin-echo sequences were used to obtain relaxation rates and proton-density maps from 1.5 T MR studies, with two axial data sets including the entire brain. Fifty normal subjects (age range, 16 to 76 years) were studied. A Three-dimensional (3D) spectrum of the tissue voxels was used for automatic segmentation of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) and for calculation of their volumes. Accuracy and reproducibility were tested with a three-compartment phantom simulating GM, WM, and CSF. In the normal subjects, a significant decrease of GM fractional volume and increased CSF volume with age were observed (P < 0.0001), with no significant changes in WM. This multispectral segmentation method permits reproducible, operator-independent volumetric measurements.

[Positron emission tomography (PET) with fludeoxyglucose F 18 in the study of adrenal masses: comparison of benign and malignant lesions]. / La tomografia con emissione di positroni (PET) con F-18 FDG nello studio delle formazioni espansive con sede surrenalica: confronto tra lesioni benigne e maligne.

In this study, 15 patients (4 men and 11 women, mean age: 50 +/- 13 years) with unilateral adrenal masses detected on ultrasound (US), Computed Tomography (CT) and/or Magnetic Resonance (MR) studies were submitted to positron emission tomography (PET) with fluorine-18 deoxyglucose (FDG). Histology demonstrated 3 adenomas, 1 myelolipoma, 1 angiolipoma, 1 neurinoma, 1 cyst, 1 malignant pheochromocytoma, 4 carcinomas and 3 metastases. The patient population was divided into two groups. Group 1 (n = 7) consisted of benign adrenal lesions. Group 2 consisted of malignant adrenal tumors. Lesion measurements were performed on the basis of the results of US, CT and/or MR images. In Group 1, no FDG uptake was observed in adrenal masses. Conversely, in Group 2 adrenal lesions showed abnormally increased FDG uptake, suggesting high glucose tumor metabolism. No significant difference in lesion size was observed between Groups 1 and 2 (5.6 +/- 4.0 vs 6.3 +/- 3.0 cm). Furthermore, in 6 patients of Group 2, total body PET images showed abnormal FDG uptake in extra-adrenal locations, such as chest (n = 2) and abdominal (n = 5) lymph nodes, lungs (n = 6), liver (n = 5), pancreas (n = 1), bone (n = 1) and muscle (n = 1) tissues. In conclusion, the results of this study suggest that PET imaging with FDG can characterize adrenal masses. In particular, abnormally increased FDG uptake in adrenal malignancies allows to differentiate these abnormalities from benign lesions. Furthermore, total body imaging PET can identify extra-adrenal tumor sites in patients with malignant tumors.

Functional characterization of brain tumors: an overview of the potential clinical value.

Early detection and characterization are still challenging issues in the diagnostic approach to brain tumors. Among functional imaging techniques, a clinical role for positron emission tomography studies with [18F]-fluorodeoxyglucose and for single photon emission computed tomography studies with [201Tl]-thallium-chloride has emerged. The clinical role of magnetic resonance spectroscopy is still being defined, whereas functional magnetic resonance imaging seems able to provide useful data for presurgical localization of critical cortical areas. Integration of morphostructural information provided by computed tomography and magnetic resonance imaging, with functional characterization and cyto-histologic evaluation of biologic markers, may assist in answering the open diagnostic questions concerning brain tumors.