We had previously reported that splice isoforms of tenascin-C containing the extra-domain C are virtually absent in normal adult tissues but are highly abundant in high-grade astrocytomas, with a prominent peri-vascular pattern of expression. We now report that the extra-domain C of tenascin-C is strongly expressed in the majority of lung cancers, with a vascular and stromal pattern of expression. Using antibody phage technology, we have generated a human monoclonal antibody (G11), with a dissociation constant K(D) = 4.2 nM for the human domain C. The G11 antibody, expressed in scFv and in mini-antibody (SIP) format, as well as a scFv-interleukin-2 fusion protein, was then characterized in quantitative biodistribution studies using mice grafted subcutaneously with U87 gliomas, revealing a selective tumor uptake, with tumor/blood ratios up to 11.8:1 at 24 h. A radioiodinated preparation of SIP(G11) was also investigated in a double tracer study using an orthotopic rat glioma model, confirming the antibody's ability to preferentially localize at the tumor site, with tumor/brain ratios superior to the ones observed with (18)F-fluorodeoxyglucose. These tumor-targeting properties, together with the strong immunohistochemical staining of human tumor sections, indicate that the G11 antibody may be used as a portable targeting moiety for the selective delivery of imaging and therapeutic agents to gliomas and lung tumors.

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Beta-probes are a relatively new tool for tracer kinetic studies in animals. They are highly suited to evaluate new positron emission tomography tracers or measure physiologic parameters at rest and after some kind of stimulation or intervention. In many of these experiments, the knowledge of CBF is highly important. Thus, the purpose of this study was to evaluate the method of CBF measurements using a beta-probe and H2 15O. CBF was measured in the barrel cortex of eight rats at baseline and after acetazolamide challenge. Trigeminal nerve stimulation was additionally performed in five animals. In each category, three injections of 250 to 300 MBq H2 15O were performed at 10-minute intervals. Data were analyzed using a standard one-tissue compartment model (K1 = CBF, k2 = CBF/p, where p is the partition coefficient). Values for K1 were 0.35 +/- 0.09, 0.58 +/- 0.16, and 0.49 +/- 0.03 mL x min(-1) x mL(-1) at rest, after acetazolamide challenge, and during trigeminal nerve stimulation, respectively. The corresponding values for k2 were 0.55 +/- 0.12, 0.94 +/- 0.16, and 0.85 +/- 0.12 min(-7), and for p were 0.64 +/- 0.05, 0.61 +/- 0.07, and 0.59 +/- 0.06. The standard deviation of the difference between two successive experiments, a measure for the reproducibility of the method, was 10.1%, 13.0%, and 5.7% for K1, k2, and p, respectively. In summary, beta-probes in conjunction with H2 15O allow the reproducible quantitative measurement of CBF, although some systematic underestimation seems to occur, probably because of partial volume effects.

Abstract. For each oncological tracer it is important to know the uptake in non-tumorous lesions. The purpose of this study was to measure the accumulation of fluorine-18 choline (FCH), a promising agent for the evaluation of certain tumour types, in infectious tissue. Unilateral thigh muscle abscesses were induced in five rats by intramuscular injection of 0.1 ml of a bacterial suspension (Staphylococcus aureus, 1.2×10 9 CFU/ml). In all animals, FCH accumulation was measured with highresolution positron emission tomography (PET) on day 6. Autoradiography of the abscess and ipsilateral healthy muscle was performed on day 7 (three animals) and day 11 (two animals) and correlated with histology. In addition, 18 F-fluorodeoxyglucose (FDG) PET was performed on day 5. Increased FCH uptake was noted in specific layers of the abscess wall which contained an infiltrate of mainly granulocytes on day 7 and mainly macrophages on day 11. The autoradiographic standardised uptake values in the most active part of the abscess wall were 2.99 on day 7 (n=3) and 4.05 on day 11 (n=2). In healthy muscle the corresponding values were 0.99 and 0.64. The abscesses were clearly visualised on the FCH and FDG PET images. In conclusion, this study demonstrated avid FCH accumulation in inflammatory tissue, which limits the specificity of FCH for tumour detection. Future studies are now needed to determine the degree of this limitation in human cancer patients.

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