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Peter Bläuenstein

Publications and source records attributed to Peter Bläuenstein.

5 recordsLinked to original sources
PubMed2003

Measurement of the extracellular space in brain tumors using 76Br-bromide and PET.

UNLABELLED: Brain edema significantly contributes to the clinical course of human brain tumor patients. There is evidence that an enlargement of the extracellular space (ECS) is involved in the development of brain edema. Although T2-weighted magnetic resonance (T2-MR) images represent brain edema by its increased water content, they do not differentiate ECS enlargement from increased intracellular water content. METHODS: On the basis of the known distribution of bromide in the ECS, we used (76)Br-bromide and PET to measure the regional ECS in 9 brain tumor patients. Transport rate constants and the distribution volume (DV) of (76)Br-bromide in normal brain and tumor were derived from dynamic PET scans and the measured (76)Br-bromide concentration in arterial plasma. We evaluated different models regarding their reliability in estimating the ECS. RESULTS: Assuming that the DV of (76)Br-bromide represents the ECS, robust estimates were possible for all investigated regions. In normal brain, ECS was within a narrow range-for example, occipital lobe, 19.9% +/- 3.1%-and was lower in 2 dexamethasone-treated patients compared with untreated patients. In 7 of 9 tumors, increased ECS ranged between 43.8% and 61.1%. ECS increases were confined to the tumor mass and did not extend into peritumoral edematous brain. Two patients with large hyperintense lesions according to T2-MR images showed normal ECS values within the lesion. CONCLUSION: (76)Br-Bromide PET allows a quantitative measurement of the ECS in brain edema and in normal brain. The discrepancies between lesions shown by T2-MRI and regional ECS enlargement as measured with PET challenge the concept of tumor-induced brain edema.

Adult↗
PubMed2002

Stabilization of neurotensin analogues: effect on peptide catabolism, biodistribution and tumor binding.

Neurotensin (NT) receptors in pancreatic and other neuroendocrine tumors are promising targets for imaging and therapeutic purposes. Here, we report on the effect of distinct changes in the peptide chain on catabolism in vitro for five radiolabeled [99mTc] neurotensin analogues having high affinity for neurotensin receptors. Substitution of NT(1-7) by (NalphaHis)Ac--the Tc-binding moiety--combined with a reduced bond 8-9 (CH2NH), N-methylation of peptide bonds or replacement of Ile(12) by tertiary leucin (Tle) led to peptide stabilization of various degrees. Biodistribution studies in nude mice bearing HT29 xenografts showed higher tumor uptake with more stable peptides, yielding high tumor to blood ratios of up to 70.

Animals↗
PubMed2002

In vitro and in vivo evaluation of a 99mTc(I)-labeled bombesin analogue for imaging of gastrin releasing peptide receptor-positive tumors.

A new radiolabeled bombesin analogue, [99mTc(I)-PADA-AVA]bombesin (7-14), was synthesized and in vitro and in vivo characterized. High affinity and rapid internalization were obtained in binding assays. A specific binding towards gastrin releasing peptide receptors-positive tissues, pancreas and tumor, was observed in CD-1 nu/nu mice bearing PC-3 prostate adenocarcinoma xenografts. We therefore conclude that [99mTc(I)-PADA-AVA]bombesin (7-14) might have promising characteristics for applications in nuclear medicine, namely for diagnosis of GRP receptor overexpressing tumors.

Adenocarcinoma↗
PubMed2002

Preclinical evaluation of a new, stabilized neurotensin(8--13) pseudopeptide radiolabeled with (99m)tc.

UNLABELLED: The rapid degradation of neurotensin (NT) limits its clinical use in cancer imaging and therapy. Thus, a new NT(8--13) pseudopeptide, NT-VIII, was synthesized. Some changes were introduced in the sequence of NT(8--13) to stabilize the molecule against enzymatic degradation: Arg(8) was N-methylated, and Lys and Tle replaced Arg(9) and Ile(12), respectively. Finally, (NalphaHis)Ac was coupled to the N-terminus for (99m)Tc(CO)(3) labeling. This peptide was characterized both in vitro and in vivo. METHODS: The new analog was labeled with (99m)Tc(CO)(3). Its metabolic stability was analyzed both in human plasma and in HT-29 cells. Binding properties, receptor downregulation, and internalization were tested with HT-29 cells. Biodistribution was evaluated in nude mice with HT-29 xenografts. RESULTS: (99m)Tc(CO)(3)NT-VIII showed a high stability in plasma, where most of the peptide remained intact after 24 h of incubation at 37 degreesC. However, the degradation in HT-29 cells was more rapid (46% of intact (99m)Tc(CO)(3)NT-VIII after 24 h at 37 degreesC). Binding to NT1 receptors (NTR1) was saturable and specific. Scatchard analysis showed a high affinity for (99m)Tc(CO)(3)NT-VIII, with a dissociation constant similar to (125)I-NT (1.8 vs. 1.6 nmol/L). After interacting with NTR1, (99m)Tc(CO)(3)NT-VIII was rapidly internalized, with more than 90% internalized after 30 min. It also distributed and cleared rapidly in nude mice bearing HT-29 xenografts. The highest rates of accumulation were found in kidney and tumor at all time points tested. Tumor uptake was highly specific because it could be blocked by coinjection with a high dose of (NalphaHis)Ac-NT(8--13). Tumors were clearly visualized in scintigraphy images. CONCLUSION: The changes that were introduced stabilized the molecule against enzymatic degradation without affecting binding properties. Moreover, the increase in stability enhanced tumor uptake, making this derivative a promising candidate for clinical use.

Adenocarcinoma↗