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Molecules. 2013 Apr 29;18(5):5005-31. doi: 10.3390/molecules18055005.

Folate-based radiotracers for PET imaging--update and perspectives.

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  • 1Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI 5232, Switzerland. cristina.mueller@psi.ch


The folate receptor (FR) is expressed in many tumor types, among those ovarian and lung cancer. Due to the high FR affinity of folic acid, it has been used for targeting of FR-positive tumors, allowing specific delivery of attached probes to the malignant tissue. Therefore, nuclear imaging of FR-positive cancer is of clinical interest for selecting patients who could benefit from innovative therapy concepts based on FR-targeting. Positron emission computed tomography (PET) has become an established technique in clinical routine because it provides an increased spatial resolution and higher sensitivity compared to single photon emission computed tomography (SPECT). Therefore, it is of critical importance to develop folate radiotracers suitable for PET imaging. This review article updates on the design, preparation and pre-clinical investigation of folate derivatives for radiolabeling with radioisotopes for PET. Among those the most relevant radionuclides so far are fluorine-18 (t(1/2): 110 min, E(av) β⁺: 250 keV) and gallium-68 (t(1/2): 68 min, E(av) β⁺: 830 keV). Recent results obtained with new PET isotopes such as terbium-152 (t(1/2): 17.5 h, Eβ⁺: 470 keV) or scandium-44 (t(1/2): 3.97 h, (Eav) β⁺: 632 keV) are also presented and discussed. Current endeavors for clinical implementation of PET agents open new perspectives for identification of FR-positive malignancies in patients.

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