Iodofalan (131I)

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Iodofalan (131I)

CAS 76641-05-9

MFC9H10131INO2

Molecular FormulaC₉H₁₀INO₂

Molecular Weight295.09

4-(131I)iodo-L-phenylalanine

(2S)-2-amino-3-(4-iodophenyl)propanoic acid
radiopharmaceutical, antineoplastic, Phase 2, Glioblastoma, 606VTF676Y, ¹³¹I-TLX-101, ACD 101

4-Iodophenylalanine I-131
4-(131I)Iodo-L-phenylalanine
4-Iodo-L-phenylalanine-131I
ACD-101
L-Phenylalanine, 4-(iodo-131I)-

OriginatorTherapeia
DeveloperTelix Pharmaceuticals; Therapeia
ClassAmino acids; Antineoplastics; Radioisotopes; Radiopharmaceutical diagnostics; Radiopharmaceuticals; Small molecules
Mechanism of ActionApoptosis stimulants; Positron-emission tomography enhancers
Orphan Drug StatusYes – Glioblastoma
Phase IIGlioblastoma
14 Oct 2025Telix Pharmaceuticals receives IND approval for TLX 101 in Glioblastoma
27 Jul 2025Telix Pharmaceuticals plans a phase III IPAX BrIGHT trial for Glioblastoma (Monotherapy, Combination therapy, Recurrent, Second-line therapy or greater) in Australia(IV) (NCT07100730)(EudraCT2025-521785-10) in September 2025
16 Apr 2025Telix has submitted for ethics approval a registration-enabling study of TLX101 in recurrent glioblastoma.

Iodofalan (131I) is a radiopharmaceutical that has garnered significant attention in oncological research due to its targeted therapeutic potential. This compound, which includes the radioactive isotope Iodine-131, has been explored for its efficacy in treating certain types of cancers, particularly those associated with the thyroid. Various research institutions worldwide have been studying Iodofalan (131I) to better understand its clinical benefits, optimize its usage, and minimize potential side effects. As a drug type, Iodofalan (131I) is categorized as a targeted radiopharmaceutical therapy, which leverages the properties of radioactive isotopes to destroy cancer cells with precision. Currently, its primary indications include differentiated thyroid cancer and non-resectable metastatic thyroid cancer, among other investigational uses.

Iodofalan (131I) Mechanism of Action

The mechanism of action for Iodofalan (131I) centers on the properties of Iodine-131, a beta-emitting isotope. When administered, Iodofalan (131I) is selectively absorbed by thyroid cells. This selectivity is due to the thyroid gland’s natural ability to uptake iodine, a key element required for the production of thyroid hormones. Cancerous thyroid tissues retain this ability, making them ideal targets for Iodofalan (131I) therapy.

Once absorbed by the thyroid cancer cells, the radioactive decay of Iodine-131 begins. This decay process emits beta particles, which possess sufficient energy to destroy nearby cells. The radiation from these beta particles causes direct DNA damage, leading to cell death. Additionally, the gamma radiation emitted by Iodine-131 can be used diagnostically to track the distribution and uptake of the compound in the body via imaging techniques such as SPECT (Single Photon Emission Computed Tomography).

The dual role of Iodofalan (131I) in both treatment and diagnostic contexts underscores its importance in managing thyroid cancers. By delivering a localized radiation dose to thyroid cancer cells, Iodofalan (131I) minimizes damage to surrounding healthy tissues, which is a significant advantage over traditional external beam radiotherapy.

What is the indication of Iodofalan (131I)?

The primary indication for Iodofalan (131I) is the treatment of differentiated thyroid cancer, a category that includes papillary and follicular thyroid cancers. These subtypes are characterized by their ability to absorb iodine, making them particularly amenable to radioiodine therapy. Iodofalan (131I) is typically used in cases where the thyroid cancer is not amenable to surgical removal or has metastasized to other parts of the body. In such scenarios, the radiopharmaceutical offers a non-invasive therapeutic option that can target and destroy cancer cells even in distant metastatic sites.

SYN

https://patentscope.wipo.int/search/en/detail.jsf?docId=US42129729&_cid=P21-MHE8B5-15309-1

EXAMPLE 1

4-Bromo-L-phenylalanine (4-BrPA), 3-bromo-L-phenylalanine (3-BrPA), 4-iodo-L-phenylalanine (4-IPA), 4-ter.butyltinn-L-phenylalanine (4-TBSnPA), 3-ter.butyltinn-L-phenylalanine (3-TBSnPA), 4-methylsilyl-L-phenylalanine (4-Me ₃SiPA) and 3-methylsilyl-L-phenylalanine (3-Me ₃SiPA) used as starting materials (precursor) for radiolabeling were either purchased commercially or prior synthesized in analogy to the literature. Unless stated otherwise, all other chemicals and solvent were of analytical grade and obtained commercially or via our local hospital pharmacy. Sodium [ ¹²⁴I]iodide, sodium [ ¹²⁵I]iodide, sodium [131I]iodide, sodium [ ⁷⁷Br]bromide, sodium [ ⁸²Br]bromide, and sodium [ ²¹¹At]astatine for radiolabeling was obtained in the highest obtainable radiochemical purity, generally in 0.01 N NaOH or in phosphate buffered saline (PBS) from different suppliers. HPLC purification was performed on a Hewlett Packard HPLC system consisting of a binary gradient pump (HP 1100), a Valco 6-port valve with 2500 μl loop, a variable wavelength detector (HP 1100) with a UV detection at 254 nm and a sodium iodide scintillation detector (Berthold, Wildbad, Germany), using reversed-phased column (250×4 mm, Nucleosil-100). The column was eluted at different flow rates in with water/ethanol/acetic acid (89:10:1; v/v) or PBS/ethanol (90:10; v/v).

The proposed radiolabeled phenylalanines were obtained either by non-isotopic halogen exchange (carrier-added/c.a.) or by radio-demetalation of the corresponding precursor as described in the general scheme 1, resulting to no-carrier-added (n. c. a) products after HPLC separation.

EXAMPLE 2

General synthesis of 3,4-[¹²⁴I]iodo-L-phenylalanine (m, p-IPA-124), 3,4-[¹²⁵I]iodo-L-phenylalanine (m,p-IPA-125) and 3,4-[¹³¹I]iodo-L-phenylalanine (m,p-IPA-131) by non-isotopic radioiodo-debromination

A solution of carrier free sodium [ ¹²⁴I]iodide, sodium [ ¹²⁵I]iodide or sodium [ ¹³¹I]iodide (up to 5 GBq) and 5 μl aqueous Na ₂S ₂O ₅(4.0 mg Na ₂S ₂O ₅/ml) was evaporated to dryness by passing a stream of nitrogen through a reaction vessel at 100° C., followed by addition of 200 μl of the corresponding L-bromophenylalanine (0.25-0.5 mg/ml 0.1 N H ₃PO ₄), 20 μl aqueous L-ascorbic acid (10 mg/ml) and 20 μl aqueous Cu(II) sulphate (0.10 mol/l). The reaction vessel was heated for 30 min at 170° C., cooled and the mixture diluted with up to 500 μl water. The radioiodinated product was separated from unreacted starting materials and radioactive impurities by HPLC.

Generally, 3/4-IPA-124, 3/4-IPA-125 and m/p-IPA-131 were obtained in 88±10% radiochemical yield, with a specific activity >500 GBq/μmol. The fraction containing the radioiodinated products was collected into a sterile tube, buffered with 0.5 M phosphate buffered saline (pH 7.0; Braun, Melsungen, Germany), and sterile filtered through a 0.22 μm sterile membrane (Millex GS, Millipore, Molsheim, France) to an isotonic and injectable radiopharmaceutical for in vitro and in vivo investigations.

PAT