Table 3.
FR-targeted nanoformulations for imaging or theranostic purposes in cancer and inflammatory diseases: PET: Positron emission tomography, SPECT: Single-photon emission computed tomography, MRI: magnetic resonance imaging, NIFI: Near infrared fluorescence imaging.
| Formulation Type | Composition | Indication | Imaging Technique | Stage | Reference | |
|---|---|---|---|---|---|---|
| Cancer | Radiolabeled FR ligands | Etarfolatide®
[99mTc]Tc-EC20 |
Identification of tumors overexpressing FRs to predict when treatment with FR-targeted therapies is a good strategy This formulation is under clinical research. | PET | Clinical trial | [100,101] |
| 3′-aza-2′-[18F]F-fluorofolic acid | Visualization of FR-positive tumor masses, evaluated in vivo in KB-derived tumors developed in mice. | PET | Pre-clinical | [102] | ||
| [18F]F-folic acid derivative | PET | Pre-clinical | [103] | |||
| [18F]F-fluorodeoxyglucose-folate | PET | Pre-clinical | [104] | |||
| [⁶⁸Ga]Ga-DOTA-folate | Visualization of FR-positive tumor masses, evaluated in vivo in KB-derived tumors developed in mice. No accumulation in HT1080-derived tumors (FR negative). | PET | Pre-clinical | [105] | ||
| [⁶⁸Ga]Ga -NODAGA-folate | Visualization of FR-positive tumor masses, evaluated in vivo in KB-derived tumors developed in mice. | PET | Pre-clinical | [106] | ||
| [⁶⁸Ga]Ga -NOTA-folate | Visualization of FR-positive tumor masses, evaluated in vivo in KB-derived tumors developed in mice. Better in vivo performance than 99mTc-EC20. | PET | Pre-clinical | [107] | ||
| 177Lu-labeled folate conjugates containing an albumin binder | Visualization of FR-positive tumor masses, evaluated in vivo in KB-derived tumors developed in mice. Better than conjugates without albumin binder. Anticancer activity in KB-derived tumors, ovarian cancer cell line overexpressing FR and in vivo breast cancer model. | PET | Pre-clinical | [108,116] | ||
| [18F]F-fluorodeoxyglucose-folate with albumin-binding capacity | Visualization of FR-positive Kidney tumor masses. Better than conjugates without albumin binder. | PET | Pre-clinical | [109] | ||
| 47Sc-labeled folate conjugates containing an albumin binder | Visualization of FR-positive Kidney tumor masses. Better than conjugates without albumin binder. Anticancer activity in KB-derived tumors and ovarian cancer cell line overexpressing FR. | PET | Pre-clinical | [110] | ||
| 152Tb-labeled folate conjugates containing an albumin binder | Visualization of KB-derived tumors. | PET | Pre-clinical | [111] | ||
| 155Tb-labeled folate conjugates containing an albumin binder | Visualization of KB-derived tumors. | SPECT | Pre-clinical | [111] | ||
| 64Cu-labeled folate conjugates containing an albumin binder | visualization of FR-positive tumors. Lower tumor-to-kidney ratio compared with other radiolabelled conjugates. | PET | Pre-clinical | [112] | ||
| 55Co-labeled folate conjugates containing an albumin binder | Visualization of FR-positive tumors. Lower tumor-to-kidney ratio compared with other radiolabelled conjugates. | PET | Pre-clinical | [113] | ||
| 177Lu-labeled MTHF conjugates containing an albumin binder | Visualization of FR-positive tumor masses due to selective targeting to FRα. | PET | Pre-clinical | [114] | ||
| [161Tb]Tb-albumin binding folate conjugate | Theracnostic purpose. Tumor visualization and anticancer activity in KB-derived tumors. | PET | Pre-clinical | [111] | ||
| [149Tb]Tb-albumin binding folate conjugate | Theranostic purpose. Tumor visualization and anticancer activity in KB-derived tumors. | PET | Pre-clinical | [111] | ||
| [90Y]Y-albumin binding folate conjugate | Theranostic purpose Anticancer activity in ovarian cancer cell line overexpressing FR. | PET | Pre-clinical | [115] | ||
| Radiolabeled anti FR-monoclonal antibodies | [111In]In-farteluzumab(anti-FRα- monoclonal antibody) and [131I]I- farteluzumab | Radioimmunoscintigraphy and possibly radioimmunotherapy of ovarian carcinomas. | SPECT | Pre-clinical | [108] | |
| Fluorescent conjugates | Folic acid-fluorescein isothiocyanate conjugates (EC17) | Visualization of tumor masses in ovarian cancer patients during the cytoreductive surgery. | NIFI | Clinical trail | [118] | |
| FR targeted nanoparticles | Mesoporous Silica nanoparticles coated with folic acid and loaded with a fluorescent agent | Visualization of pancreatic tumors overexpressing FR. | NIFI | Pre-clinical | [119] | |
| Silica nanoparticles coated with folic acid and loaded with a phosphorescent agent | In vitro evaluation of FR expression in cervical cancer cells. | Phosphorescence Lifetime Imaging | Pre-clinical | [120] | ||
| Gold nanostars covered with a silica shell that is functionalized with anti-FRα-monoclonal antibodies | Visualization of ovarian tumors | Raman imaging | Pre-clinical | [121] | ||
| Mesoporous silica nanoparticles loaded with perfluorohexane and coated with indocyanine green and folic acid | Treatment and imaging or breast carcinomas | NIFI | Pre-clinical | [123] | ||
| Folic acid-coated nanoparticles loaded with perfluorohexane and paclitaxel green indocyanine | Ultrasound imaging | Pre-clinical | [124] | |||
| Gold-albumin nanoparticles coupled with folic acid and loaded with doxorubicin | Treatment and imaging or FR-positive gastric cancer cells | Tomography imaging | Pre-clinical | [125] | ||
| Arthritis | FR targeted nanoparticles for imaging | Folic acid-coated iron oxide nanoparticles | Inflammation site visualization | MRI | Pre-clinical | [126] |
| Ulcerative colitis | FR targeted nanoparticles for theragnosis | Liposomes coated with folic acid and loaded with betamethasone and a fluorescent dye | Inflammation site visualization and anti-inflammatory effect | NIFI | Pre-clinical | [127] |