Tumour angiogenesis pathways: Related clinical issues and implications for nuclear medicine imaging

Tumour angiogenesis is essential for growth, invasion and metastasis. Retrospective studies suggest that it is an independent prognostic factor that merits prospective validation. Furthermore, as tumour blood vessels show many differences from normal vessels and are not genetically unstable, they form a key area for therapy development. However, as anti-angiogenic therapy is primarily cytostatic and not cytotoxic, novel tailormade specific end-points for treatment monitoring are required. In this regard, suitable molecular parameters for imaging tumour angiogenesis by means of nuclear medicine are being explored. Here we review current knowledge on the multiple pathways controlling tumour angiogenesis and try to assess which are the most clinically relevant for nuclear medicine imaging. Parameters that may influence the imaging potential of radiopharmaceuticals for angiogenesis imaging such as molecular weight and structure, their targeted location within the tumour and their usefulness in terms of specificity and constancy of the targeted molecular pathway are discussed

Tryptophane-based biphenylsulfonamide matrix metalloproteinase inhibitors as tumor imaging agents

Aim: As a part of our efforts to use small organic matrix metalloproteinase (MMP) inhibitors with improved characteristics for the diagnosis and treatment of different kinds of tumor tissues, biphenylsulfonamide analogues were synthesized. This study reports on the in vivo biodistribution of iodine-123-labeled biphenylsulfonide and analogues in A549 lung carcinoma inoculated into athymic mice and the evaluation of their suitability as imaging agents using a single photon emission computed tomography (SPECT) camera. Methods: The radioiodinated carboxylic and hydroxamic MMP inhibitors 2-(4′- [123I]iodobiphenyl-4-sulfonylamino)-3-(1H-indol-3-yl)-propionic acid (1′) and 2-(4′-[123I]iodobiphenyl-4- sulfonylamino)-3-(1H-indol-3-yl)-propionamide (2′) were synthesized by electrophilic aromatic substitution of the tributylstannyl derivatives. Planar gamma camera imaging was performed in nu/nu athymic mice bearing an A549 tumor using a Toshiba GCA-9300A/hg SPECT camera in planar mode equipped with a high-resolution, parallel-hole collimator. Results: Radiosynthesis of (1′) and (2′) resulted in radiochemical yields of 60 ± 5% (n ± 3) and 70 ± 5% (n = 6), respectively. Evaluation of tumors induced in athymic mice by the inoculation of non-small cell lung A549 carcinoma cells, showed a tumor uptake of 0.27–0.01 percent injected dose per gram (%ID/g) (3 hours–48 hours p.i.), a tumor-blood ratio of 0.7, a tumor-muscle ratio of 1.6, and a tumor-fat ratio of 0.5 at 24 hours (p.i.) for compound 1′. For compound 2′ a tumor uptake of 0.7–0.04 %ID/g (3 hours–48 hours p.i.), a postinjection tumor-blood ratio of 1.2, a tumor-muscle ratio of 3.2, and a tumor-fat ratio of 2.4 at 48 hours p.i. was observed. SPECT evaluation confirmed the results obtained from biodistribution. Conclusion: In vivo evaluation of these radioiodinated carboxylic and hydroxamic MMP inhibitor tracers revealed that they do not appear suitable as tumor-imaging agents