Covalent core-radiolabeling of polymeric micelles with125I/211At for theranostic radiotherapy

• Astatine-211 (211At) is one of the most promising α-emitters for targeted alpha therapy, especially of cancer metastases. However, the lack of a stable isotope, frequent in vivo deastatination, and limited radiochemical knowledge makes it challenging to apply. Here, we report a new strategy for radiolabeling the lipophilic core of polymeric micelles (PMs) with covalently bound211At. The PMs were radiolabeled via either an indirect synthon-based method or directly on the amphipathic block copolymer. The radiochemistry was optimized with iodine-125 (125I) and then adapted for211At, enabling the use of both elements as a potential theranostic pair. PMs that were core-radiolabeled with both125I or211At were prepared and characterized, based on a PEG(5k)-PLGA(10k) co-polymer. The stability of the radiolabeled PMs was evaluated in mouse serum for 21 h, showing radiochemical stability above 85%. After in vivo evaluation of the211At-labeled PMs, 4-5 % ID/g of the211At could still be detected in the blood, showing a promising in vivo stability of the PMs. Further,211At-labeled PMs accumulated in the spleen (20-30 %ID/g) and the liver (2.5-5.5 %ID/g), along with some detection of211At in the thyroid (3.5-9 %ID/g). This led to the hypothesis that deastatination takes place in the liver, whereas good stability of the211At core-radiolabel was observed in the blood. © The author(s).

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)

Keyword

alpha-therapy

Astatine-211

iodine-125

PEG-PLGA

polymeric micelles

2

5 dioxopyrrolidin 1 yl 3 iodobenzoate

2

5 dioxopyrrolidin 1 yl 3 (astato 211At) benzoate

2

5 dioxopyrrolidin 1 yl 3 (iodo iodine 125) benzoate

2

5 dioxopyrrolidin 1 yl 3 (trimethylstannyl) benzoate

3 (astato astatine 211) benzamide n (polyethylene glycol poly(lactic co glycolic acid)

3 (iodo iodine 125) benzamide n (polyethylene glycol poly(lactic co glycolic acid)

3 (trimethylstannyl)benzamide n (polyethylene glycol poly(lactic co glycolic acid)

aluminum

astatine 211

bismuth

germanium

iodine 125

macrogol

n chlorosuccinimide

n iodosuccinimide

n

n dimethylformamide

polyglactin

polymer

sodium iodide

succinimidyl stannyl enzoate

tosylchloramide sodium

unclassified drug

adult

animal experiment

animal model

animal tissue

Article

biodistribution

bond strength

carbon nuclear magnetic resonance

chromatography

circulation

clinical evaluation

controlled study

covalent bond

drug stability

dry distillation

female

high performance liquid chromatography

hydrophophicity

incubation time

lipophilicity

macrophage activation

micelle

mouse

nonhuman

particle size

photon correlation spectroscopy

polymeric micelle

positron emission tomography

proton nuclear magnetic resonance

purification

radiochemical conversion

radiochemical stability

radiochemistry

radiohalogenation

radioiodination

radiolabeling

theranostic nanomedicine

theranostic radiotherapy

thin layer chromatography

transmission electron microscopy

zeta potential

Publication and Content Type

ref (subject category)

art (subject category)