Submitted by Mi.Varokky@iaea.org on
Project Code
F22064
2002
Status
Project Author
INTERNATIONAL ATOMIC ENERGY AGENCY
Approved Date
Start Date
Expected End Date
Completed Date
CRP Closed Date
Description

The aim of this CRP is to provide significant improvement in the delivery of therapeutic radiopharmaceuticals through the use of nanotechnology. It is expected to result in new nanoparticles capable of forming stable bonds with diagnostic and therapeutic radioisotopes, and with tumour specific biomolecules and proteins (including monoclonal antibodies) leading to well-defined delivery devices. Such nano constructs built from radiation-synthesized polymeric nano particles could be potentially capable of reaching and selectively penetrating the tumour sites, thus affording highly effective molecular imaging and therapeutic tools to combat various forms of human cancers. The proposed CRP will provide tremendous benefits to MS because the nanosized diagnostic and therapeutic agents that are planned to be developed might be potentially used in alleviating pain and suffering of human patients globally.

Objectives

The overall objective of this CRP is to exploit the unique properties of materials at the nanometer scale for developing nanocarriers of radioactivity capable of selectively targeting and penetrating cancerous cells.

Specific objectives

a; To synthesize polymeric (both synthetic and natural) nanoparticles capable of forming in vitro and in vivo-stable bonds, through chelate interactions, with diagnostic and therapeutic radioisotopes—for the creation of new generation of nanoparticle-based tumor specific radiopharmaceuticals.

b; To formulate tumor specific proteins (including monoclonal antibodies) and generate well-defined nanoparticles, through radiation methods, for use in conjugation reactions with diagnostics and therapeutic radioisotopes for the generation of nanosized tumor specific radiopharmaceuticals.

c; To formulate nanoparticles derived from inherently diagnostic/ therapeutic radioisotopes and to conjugate them with tumor specific peptide(s)—in order to generate radioactive nanoceuticals for diagnostic imaging and therapy.

d; To develop a functional in vivo platform for efficient testing of various radiolabeled nanoconstructs using animal models that mimic human tumors—all aimed at clinical translation of diagnostic/therapeutic efficacy from animal for human applications.

Impact

The participants suggested initiation of a new CRP for completion of preclinical studies of the selected nanoconstructs (with focus on Ga-68, Lu-177 and Au-198 radionuclides)
The participants emphasized on initiation of a new CRP on one selected nanoconstruct from this CRP (MGF 198AuNPs)with completed preclinical results) through IAEA NAHU, nuclear medicine section
Instant initiation of an IAEA publication on the ‘Development of radiolabeled nanoparticles for theranostic applications” as an outcome of this CRP with the help of the participants and world-class scientists
Preparation of an IAEA publication on “Guidelines on the development of human tumour models for preclinical studies of radiopharmaceuticals”
A new activity on the clinical evaluation of chemical and radiation produced 99mTc-Nanocolloids for sentinel node scintigraphy through IAEA NAHU, nuclear medicine section
The participants agreed that the report to be kept confidential among the participants and not to be shared publicly. As soon as the participants announce their willingness for public access, the scientific secretary will initiate publishing the report as a ‘working material”

Relevance

The currently used therapeutic agents in nuclear medicine continue to pose medical challenges mainly due to the limited uptake of radiocompound within tumour sites. This limited accumulation accounts for the fact that current beta-emitting therapeutic nuclear medicine agents have failed to deliver optimum therapeutic payloads at tumour sites. Actually, no other radiolabelled therapeutic agent has been capable to get close to the remarkably high target accumulation that was demonstrated by the long-lasting radionuclide I-131 in thyroid cancer. This means that metastases of several different types of aggressive cancers cannot be controlled, making it difficult to treat cancer patients. Therefore, new delivery modalities that result in (i) effective delivery of therapeutic probes with optimum payloads, site specifically at the tumour sites, minimal/tolerable systemic toxicity, and (ii) higher tumour retention, would bring about a clinically measurable shift in the way cancers are diagnosed and treated.
Nanotechnology has the potential to bring about this paradigm shift in the early detection and therapy of various forms of human cancers because radioactive nanoparticles of optimum sizes for penetration across tumour cell membranes can be engineered through a myriad of interdisciplinary approaches, involving teams of experts from nuclear medicine, materials sciences, physics, chemistry, tumour biology and oncologists. Therefore, the overall approach which encompasses application of nanoparticulate radioactive probes in combination with polymeric nanomaterials has a realistic potential to generate the next generation of tumour specific theranostic nanoradiopharmaceuticals and minimize/eliminate delivery and tumour accumulation problems associated with the existing traditional nuclear medicine agents.

CRP PO1 Name
JALILIAN,Amirreza
CRP PO1 Email
A.Jalilian@iaea.org
CRP PO1 Section
RCRTS - Radiochemistry and Radiation Technology Section (RCRTS)
CRP PO1 Division
NAPC - Division of Physical and Chemical Sciences
CRP Open for proposals
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