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Folate Receptor-Targeted Radionuclide Imaging Agents

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Targeted Drug Strategies for Cancer and Inflammation

Abstract

Diagnostic nuclear medicine makes use of two molecular imaging ­technologies, single-photon emission computed tomography (SPECT) and positron emission tomography (PET). SPECT and PET can be used to noninvasively identify and localize cancerous tumors through the use of marker proteins which are overproduced in cancer cells. The folate receptor (FR) is one such protein which is overexpressed in a variety of cancer types, with highest frequency observed in ovarian and endometrial carcinomas (>95% of the cases). The FR is therefore an ideal structure for nuclear imaging using FR-targeted radiopharmaceuticals. A variety of folic acid conjugates have been developed with chelating systems suitable for radiolabeling with SPECT isotopes (99mTc, 111In, 67Ga) and PET isotopes (66/68Ga, 64Cu, 18F). Virtually all folate radiotracers bind specifically to FR-positive cancer cells (e.g., KB, M109, 24JK-FBP) in vitro. Similarly, in vivo FR-specific tumor accumulation using the same radiotracers has been studied in tumor bearing mice. However, the in vivo tissue distribution varies significantly among different radiofolates and is well correlated with the compound’s hydrophobicity. The uptake of radiofolates in FR-positive tumors is generally high and receptor specific. Undesired accumulation of radioactivity in the intestinal tract has been found primarily with strongly lipophilic derivatives, whereas almost exclusive renal elimination has been observed to occur with more hydrophilic conjugates. As a consequence of the specific binding to FRs that are expressed in renal proximal tubule cells, all radiofolates accumulate in the kidneys. Although this feature is less critical from a dosimetric point of view for most radionuclides used for SPECT and PET, it is still undesirable because this feature obscures identification of radiofolate uptake in small lesions. Thus, the development of methods to reduce kidney uptake is of importance both for diagnostic applications of folate-based radioimaging agents and for potential therapeutic applications using particle-emitting folate radioconjugates. This chapter will review the state of the art of folate-targeted radioconjugates and related imaging and therapeutic applications.

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Authors and Affiliations

  1. Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen-PSI, Switzerland

    Cristina Müller

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  1. Cristina Müller
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  2. Roger Schibli
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Correspondence to Cristina Müller .

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  1. Section of Medicine, Institute of Cancer Research, Cotswold Road 15, Sutton, SM2 5NG, United Kingdom

    Ann L. Jackman

  2. Endocyte Inc., Kent Avenue 3000, West Lafayette, 47906, Indiana, USA

    Christopher P. Leamon

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Müller, C., Schibli, R. (2011). Folate Receptor-Targeted Radionuclide Imaging Agents. In: Jackman, A., Leamon, C. (eds) Targeted Drug Strategies for Cancer and Inflammation. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-8417-3_4

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