GLUT 5 is not over-expressed in breast cancer cells and patient breast cancer tissues.

F18 2-Fluoro 2-deoxyglucose (FDG) has been the gold standard in positron emission tomography (PET) oncologic imaging since its introduction into the clinics several years ago. Seeking to complement FDG in the diagnosis of breast cancer using radio labeled fructose based analogs, we investigated the expression of the chief fructose transporter-GLUT 5 in breast cancer cells and human tissues. Our results indicate that GLUT 5 is not over-expressed in breast cancer tissues as assessed by an extensive immunohistochemistry study. RT-PCR studies showed that the GLUT 5 mRNA was present at minimal amounts in breast cancer cell lines. Further knocking down the expression of GLUT 5 in breast cancer cells using RNA interference did not affect the fructose uptake in these cell lines. Taken together these results are consistent with GLUT 5 not being essential for fructose uptake in breast cancer cells and tissues.

Chemoselective hydrazone formation between HYNIC-functionalized peptides and (18)F-fluorinated aldehydes.

INTRODUCTION: Since the demand for (18)F-fluorinated peptides for quantitative in vivo receptor imaging using PET has increased, a new chemoselective two-step (18)F-labeling strategy based on hydrazone formation between an unprotected hydrazine-functionalized peptide and an (18)F-labeled aldehyde was developed. METHODS: First, 4-[(18)F]fluorobenzaldehyde ([(18)F]FB-CHO) was prepared from 4-formyl-N,N,N-trimethylanilinium triflate via direct no-carrier-added (18)F-fluorination (dimethyl sulfoxide, 90 degrees C, 5 min) and purified by RP-HPLC. Hydrazone formation between [(18)F]FB-CHO and 6-hydrazinonicotinic acid (HYNIC) and the unprotected HYNIC-functionalized peptides (HYNIC-d-Phe(1))-Tyr(3)-Thr(8)-octreotide and (HYNIC-Arg(1))-substance P was evaluated with respect to the dependence of radiochemical yield on pH, precursor concentration and temperature. The stability of [(18)F]FB-CH=N-HYNIC-Tyr(3)-Thr(8)(NH(2))-octreotide in aqueous solution at various pH (4.0, 5.5 and 7.5) as well as the in vivo stability of [(18)F]FB-CH=N-HYNIC-Tyr(3)-Thr(8)-octreotide in mouse blood (30 min p.i.) was investigated. RESULTS: Yields of the hydrazone formation were independent of pH between pH 0.5 and 5.5. Optimal labeling yields of 85% were obtained with a precursor concentration of 2.1 mM at 70 degrees C for 10 min. The labeling products were stable at pH 7.5 at 37 degrees C, while in more acidic media (pH 4.0) the product slowly decomposed to form up to 31+/-2% [(18)F]FB-CHO within 5 h. Metabolite studies showed no detectable degradation of [(18)F]FB-CH=N-HYNIC-Tyr(3)-Thr(8)-octreotide in mouse blood (30 min p.i.). CONCLUSIONS: In conclusion, chemoselective hydrazone formation between unprotected HYNIC-functionalized peptides and [(18)F]FB-CHO is a fast and straightforward radiolabeling method leading to high yields under mild acidic conditions. In addition, it represents a powerful and versatile radiolabeling strategy that is applicable to a variety of radionuclides and peptide precursors already available for (99m)Tc labeling.

[123I]Mtr-TOCA, a radioiodinated and carbohydrated analogue of octreotide: scintigraphic comparison with [111In]octreotide.

PURPOSE: Scintigraphy with maltotriose-[123I]Tyr3-octreotate ([123I]Mtr-TOCA) is compared with [111In]DTPA-Phe1-octreotide ([111In]OC) to assess the differences in pharmacokinetics and imaging properties as well as to estimate the therapeutic potential of the corresponding [131I]Mtr-TOCA. METHODS: Six patients with somatostatin receptor (sstr)-positive tumours were assessed using a dual-head gamma camera. After injection of 137 +/- 28 MBq [123I]Mtr-TOCA, dynamic data acquisition of the upper abdomen (30 min) was performed followed by whole-body scans at 0.5 h, 1 h, 3 h and 20 h as well as by SPECT imaging (tumour) at 2 h. [111In]OC scintigraphy was performed by acquiring whole-body scans (4 h, 24 h) and SPECT (24 h). Using a region of interest (ROI) method, tissue and tumour bound activity was assessed and dosimetry performed. RESULTS: [123I]Mtr-TOCA shows rapid tumour uptake. Up to 4 h, tumour/organ (tu/org) ratios are stable and generally higher than with [111In]OC. From 3 h to 20 h, tu/org ratios increase for spleen, remain stable for liver and decrease significantly for all other tissues. In contrast, with [111In]OC, tu/org ratios decrease slightly between 4 h and 24 h for liver, spleen and kidney and increase for all other tissues. On [123I]Mtr-TOCA scintigraphy, a total of 27 lesions are detected, whereas 33 lesions are detected on [111In]OC scintigraphy (p=0.50). Effective patient absorbed dose is 1.9 +/- 0.9 mSv per 100 MBq [123I]Mtr-TOCA. CONCLUSION: Compared with [111In]OC, [123I]Mtr-TOCA enables faster imaging of sstr-positive tumours with a lower radiation burden to the patient. [123I]Mtr-TOCA and [111In]OC allow for tumour imaging with almost identical contrast and diagnostic yield. As regards peptide receptor radionuclide therapy, radioiodinated Mtr-TOCA is hampered by limited intratumoural activity retention

Radiolabeled carbohydrated somatostatin analogs: a review of the current status.

During the last decade, peptide radiopharmaceuticals have become an important class of tracers for the detection and localization of malignant neoplasms by peptide receptor imaging (PRI) and for therapeutic intervention by peptide receptor radiotherapy (PRRT). Various radiometalated peptides have entered detailed clinical studies or found broad application for peptide receptor radiotherapy. In contrast, radiohalogenated peptides could not benefit from this development. Especially with respect to the growing number of peptidic structures with high receptor affinity and the increasing demand for means of corresponding receptor status quantification for therapy planning and control, the development of methods for the improved availability of 18F-labeled peptides for positron emission tomography imaging is still a very important objective in radiopharmaceutical research. Consequently, as part of our ongoing efforts in this field, we investigated the potential of carbohydration as a valuable tool to modify pharmacokinetics of peptides and evaluated the influence of this modification on the in vitro and in vivo behavior of octreotide analogs. Furthermore, a new methodology is presented allowing for the fast and straightforward labeling of peptides in a chemoselective manner. This combined approach to the chemoselective conjugation of unprotected, carbohydrated peptides seems to have the potential for a redirection and reevaluation of the future of radiohalogenated peptides in nuclear medicine.