Biomedical subjects

Josef Doll

Publications and source records attributed to Josef Doll.

3 recordsLinked to original sources

PubMed2005

GRP receptor-targeted PET of a rat pancreas carcinoma xenograft in nude mice with a 68Ga-labeled bombesin(6-14) analog.

UNLABELLED: Bombesin (BN), a 14-amino-acid peptide, shows high affinity for the human gastrin-releasing peptide receptor (GRP-r), which is overexpressed on several types of cancer, including prostate, breast, gastrointestinal, and small cell lung cancer. Thus, radiolabeled BN or BN analogs may prove to be specific tracers for diagnostic and therapeutic targeting of GRP-r-positive tumors in nuclear medicine. This study evaluated a novel BN analog labeled with the positron emitter 68Ga for receptor imaging with PET. METHODS: DOTA-PEG2-[D-Tyr6,beta-Ala11,Thi13,Nle14] BN(6-14) amide (BZH3) (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid; PEG is ethyleneglycol (2-aminoethyl)carboxymethyl ether) was synthetized using the Fmoc strategy and radiolabeled with either 67Ga or 177Lu for in vitro and biodistribution experiments. 68Ga for PET was obtained from a 68Ge/68Ga generator. In vitro binding, internalization, and efflux were determined using the pancreatic tumor cell line AR42J. Biodistribution of the peptide as a function of time and dose was studied in AR42J tumor-bearing mice. RESULTS: In vitro assays demonstrated a high affinity of 67Ga-BZH3 (dissociation constant = 0.46 nmol/L), a rapid internalization (70% of total cell-associated activity was endocytosed after a 15-min incubation), and an intracellular retention half-life (t1/2) of the 67Ga activity of 16.5 +/- 2.4 h. Biodistribution indicated a dose-dependent uptake in the tumor and a prolonged tumor residence time (t1/2 approximately 16 h). Clearance from GRP-r-negative tissues was fast, resulting in high tumor-to-tissue ratios as early as 1 h after injection. Replacing 67Ga by 177Lu, a therapeutic radionuclide, for peptide labeling resulted in a slightly reduced (approximately 20%) tumor uptake and tumor residence time of 177Lu-BZH3. In contrast, 177Lu decline in the pancreas was significantly accelerated by a factor of 3 compared with that of 67Ga. PET of mice with 68Ga-BZH3 clearly delineated tumors in the mediastinal area. CONCLUSION: The promising in vivo data of 68Ga-BZH3 indicate its potential for an improved localization of GRP-r-positive tumors and also suggest its application in patients. PET may also be favorably used for GRP-r density determination, a prerequisite for therapeutic applications.

Animals↗

PubMed2005

Characterization of 68Ga-DOTA-D-Phe1-Tyr3-octreotide kinetics in patients with meningiomas.

UNLABELLED: Because biopsy has a high risk of hemorrhage and the findings of CT and MRI are often ambiguous, especially at the base of the skull, additional methods for the characterization of intracranial tumors are needed. Meningiomas show high expression of the somatostatin receptor subtype 2 and thus offer the possibility of receptor-targeted imaging. We used the somatostatin analog (68)Ga-DOTA-d-Phe(1)-Tyr(3)-octreotide (DOTA-TOC) labeled with the positron emitter (68)Ga (half-life, 68 min), obtained from a (68)Ge/(68)Ga generator, for PET of these tumors. In contrast to (18)F-FDG, this ligand shows high meningioma-to-background ratios. The aim was to evaluate kinetic parameters in meningiomas before radiotherapy. METHODS: Dynamic PET scans (3-dimensional mode; 28 frames; ordered-subsets expectation maximization reconstruction) were acquired for 21 patients (mean age +/- SD, 51 +/- 13 y) before radiotherapy during the 60 min after intravenous injection of 156 +/- 29 MBq of (68)Ga-DOTA-TOC. We analyzed 28 meningiomas (median grade [I] according to the system of the World Health Organization) with volumes of at least 0.5 mL (mean volume, 13.1 mL) and nasal mucosa as reference tissue, showing a slight to moderate physiologic uptake. For evaluation of the (68)Ga-DOTA-TOC kinetics, the vascular fraction (vB) and the rate constants (k1, k2, k3, and k4 [1/min]) were computed using a 2-tissue-compartment model. Furthermore, receptor binding (RB) (k1 - k1 x k2) and the ratios k1/k2 and k3/k4 were calculated. RESULTS: Significant differences (P < 0.05; t test) between meningiomas and the reference tissue were found for the mean standardized uptake value (10.5 vs.1.3), vB (0.42 vs. 0.11), k2 (0.12 vs. 0.56), k3 (0.024 vs. 0.060), k4 (0.004 vs. 0.080), and RB (0.49 vs. 0.13). Although there was no significant difference for k1 (0.54 vs. 0.40), the ratios k1/k2 (4.50 vs. 0.71) and k3/k4 (6.00 vs. 0.75) were markedly greater in meningiomas than in reference tissue. CONCLUSION: The high uptake of (68)Ga-DOTA-TOC in meningiomas can be explained by the high values for vB and by the remarkably low values for k2 and k4, leading to significantly greater k1/k2 and k3/k4 ratios and RB in meningiomas than in reference tissue. Thus, pharmacokinetic modeling offers a more detailed analysis of biologic properties of meningiomas. In further studies, these data might serve as a basis for monitoring the somatostatin receptors of meningiomas after radiotherapy.

Adult↗

PubMed2002

Fast implementation of the single scatter simulation algorithm and its use in iterative image reconstruction of PET data.

In positron emission tomography (PET), scatter correction is usually performed prior to image reconstruction using a more or less exact model of the scatter processes. These models require estimates of the true activity and object density distributions of the imaged object. The problem is that these estimates are computed from measured data and, therefore, already contain scattered events. The purpose of this work was to overcome this problem by incorporating scatter characteristics directly into the process of iterative image reconstruction. This could be achieved by an optimized implementation of the single scatter simulation (SSS) algorithm, which results in a significant speed-up of the scatter estimation procedure. The scatter simulation was then included in the forward projection step of maximum likelihood image reconstruction. The results demonstrate that this approach leads to a more exact estimation of the scatter component which cannot be obtained by a simple sequential data processing strategy.

Algorithms↗