Modulation of [5-125I]iododeoxyuridine incorporation into tumour and normal tissue DNA by methotrexate and thymidylate synthase inhibitors.

A potentially useful method for imaging of micrometastases and in situ radiotherapy, would be the incorporation of radioactive labelled iododeoxyuridine (IdU) into tumour DNA. However, there are two main problems: incorporation of the radioactive IdU into normal cells and low incorporation into tumour cells. The aim of this study was to attempt to augment the incorporation of [5-125I]iododeoxyuridine (125IdU) into tumour DNA and to improve the tumour/normal tissue ratio by the use of inhibitors (methotrexate, 5-fluorouracil, AG337, ZD 1694, benzyloxybenzyl uracil) which would prolong the metabolic half-life of the compound.

Mutations in the estrogen receptor gene.

Somatically generated mutations in the estrogen receptor (ER) have been found at the mRNA/cDNA level in human breast cancer biopsies and in established breast cancer cell lines. Aberrantly spliced ER mRNA causes the appearance of truncated or internally deleted ER protein forms. Studies on the functional activity of the ER variants in expression systems have revealed dominant-positive receptors that are transcriptionally active in the absence of estrogen, and dominant-negative receptors that are themselves transcriptionally inactive but that prevent the action of the normal receptor.

Metabolism of a [18F]fluorine labeled progestin (21-[18F]fluoro-16 alpha-ethyl-19-norprogesterone) in humans: a clue for future investigations.

Assessment of estrogen receptors and progesterone receptors (PR) with PET may allow the determination of the hormone responsiveness of tumors without the need for multiple biopsies, and the monitoring of the effect of hormonal therapy. In spite of the favourable characteristics of 21-[18F]fluoro-16 alpha-ethyl-19-norprogesterone ([18F]FENP) found in preclinical studies, the compound failed to reveal the presence of PR in breast carcinomas and meningiomas. In view of the clinical significance of the PR assay in human breast cancer, it is worthwhile to explore mechanisms that are potentially involved in the inadequacy of [18F]FENP to image PR with PET.