RADIODRUG FOR DIAGNOSTIC/THERAPEUTIC USE IN NUCLEAR AND RADIO-GUIDED MEDICINE
The theragnostic radiopharmaceutical is structurally related to the neurotransmitter norepinephrine which, because of this similarity, is the substrate of the axonal norepinephrine transporter (NET). Depending on the specific radiometal incorporated, this radiopharmaceutical can be potentially useful both as a tracer for the surgical removal guided by beta minus radiation and for diagnostic imaging and radiometabolic therapy of the neuroendocrine tumors that over-express the NET (pheochromocytomas, paragangliomas, neuroblastomas, etc.).
The theragnostic radiopharmaceutical (RP) consists of 4 main portions: a pharmacophoric group which mimics the neurotransmitter norepinephrine (NE) and contributes to making the RF in its entirety as a preferential substrate of the NE transporter (NET), a connection unit to which a bifunctional chelating group is linked, and finally a trivalent radioactive metal cation. This RP has the ability to be preferably detected by tumor cells that over-express the NET, along with a low intrinsic toxicity. This RP, if labeled with a pure β- emitter such as 90Y3+ and used in combination with the probe (PCT/IT 2014/000025), potentially allows to extend the application field of radio-guided surgery (RGS) to neuroendocrine tumors which over-express the NET for which until now the RGS has been substantially ineffective. A technological advantage of this RP over the MIBG (Meta-Iodo-Benzyl-Guanidine), the current gold standard among theragnostics used in tumors over-expressing the NET, is that, since in the absence of a radiometal chelated inside the resulting molecule loses the ability to be a NET substrate, the RP can be used in theragnostics in the presence of a large excess of the unlabeled precursor. Therefore, even if prepared with simplified and fast procedures that exclude the always expensive final step of post-labeling purification, it can be formulated and used in preparations with low specific activity. The RP can have different applications depending on the specific radiometal incorporated.
- If labeled with 90Y3+ can be used as tracer for the surgical removal guided by β- radiation of neuroendocrine tumors that over-express the NET (carcinoid cancers, thyroid marrow cancers, etc.) ;
- If labeled with 68Ga3+ or 111In3+ can be used for PET or SPECT imaging of NET positive tumors;
- If labeled with 177Lu3+ it can act as a proper theragnostic for radiometabolic therapy and for the simultaneous scintigraphy imaging of NET positive tumors.
- If labeled with 90Y3+, exploiting the lower penetration of power of β- emission compared to γ rays, allows to extend the application of radio-guided surgery (RGS) to NET positive tumors overcoming the limits of the actual “gold standard” γ emitter MIBG;
- Simplified, fast & low-cost preparation procedure;
- Can be formulated in highly effective low specific activity preparations;
- Multiple theragnostic applications for NET positive tumors.