Imaging hypoxia and angiogenesis in tumors

Abstract

There is a clear need in cancer treatment for a noninvasive imaging assay that evaluates the oxygenation status and heterogeneity of hypoxia and angiogenesis in individual patients. Such an assay could be used to select alternative treatments and to monitor the effects of treatment. Of the several methods available, each imaging procedure has at least one disadvantage. The limited quantitative potential of single-photon emission CT and MR imaging always limits tracer imaging based on these detection systems. PET imaging with FMISO and Cu-ATSM is ready for coordinated multicenter trials, however, that should move aggressively forward to resolve the debate over the importance of hypoxia in limiting response to cancer therapy. Advances in radiation treatment planning, such as intensity-modulated radiotherapy, provide the ability to customize radiation delivery based on physical conformity. With incorporation of regional biologic information, such as hypoxia and proliferating vascular density in treatment planning, imaging can create a biologic profile of the tumor to direct radiation therapy. Presence of widespread hypoxia in the tumor benefits from a systemic hypoxic cell cytotoxin. Angiogenesis is also an important therapeutic target. Imaging hypoxia and angiogenesis complements the efforts in development of antiangiogenesis and hypoxia-targeted drugs. The complementary use of hypoxia and angiogenesis imaging methods should provide the impetus for development and clinical evaluation of novel drugs targeted at angiogenesis and hypoxia. Hypoxia imaging brings in information different from that of FDG-PET but it will play an important niche role in oncologic imaging in the near future. FMISO, radioiodinated azamycin arabinosides, and Cu-ATSM are all being evaluated in patients. The Cu-ATSM images show the best contrast early after injection but these images are confounded by blood flow and their mechanism of localization is one step removed from the intracellular O2 concentration. FMISO has been criticized as inadequate because of its clearance characteristics, but its uptake after 2 hours is probably the most purely reflective of regional PO2 at the time the radiopharmaceutical is used. The FMISO images show less contrast than those of Cu-ATSM because of the lipophilicity and slower clearance of FMISO but attempts to increase the rate of clearance led to tracers whose distribution is contaminated by blood flow effects. For single-photon emission CT the only option is radioiodinated azamycin arabinosides, because the technetium agents are not yet ready for clinical evaluation. Rather than develop new and improved hypoxia agents, or even quibbling about the pros and cons of alternative agents, the nuclear medicine community needs to convince the oncology community that imaging hypoxia is an important procedure that can lead to improved treatment outcome.