Table 1.

Diagnostic systems developed by Italian research groups. The works reported in the table have been selected to showcase a range of recent advances from Italian research groups across the different areas of diagnostic medicine, favoring the most recent and/or the more advanced works.

Formulation Strategy	Formulation Innovation	Imaging Probe	Imaging Technique	Application	Tests	Ref.
Chemical modification, prodrugs and bio-precursors	Insertion of a deuterium atom in [18F]fluoromethyl-PBR28	18F	PET	Detection of inflammation associated to TSPO overexpression; diagnosis of neuroinflammation, neurodegeneration, and tumor progression	In vitro: human leukocyte membranes and rat cerebrocortical samples; Ex vivo: ICR mice In vivo: rat models of LPS-induced inflammation and of experimental autoimmune myocarditis	[24,25]
	Fluorine-substituted TSPO ligand	18F	PET	Detection of neuroinflammation, neurodegeneration, and tumor progression	Ex vivo: ICR mice In vivo: U87-MG xenografted Balb/c nu/nu mice	[17]
Use of buffers	Use of lactate buffer for [18F]F-DOPA dissolution	18F	PET	Detection of loss of functional dopaminergic neuron terminals in the striatum	In vitro: mouse skeletal muscle fibers In vivo: Wistar rats and C57BL/6J mice	[26]
Conjugates for active targeting	Synthesis of dextran-based multifunctional ligands	99mTc	Lymphoscintigraphy	Sentinel lymph node detection for diagnosis of different types of cancers	In vitro: stability monitored in saline or serum	[27]
	Conjugation of an albumin derivative with a DOTA ring	177Lu, 111In, 64Cu	PET	Radio-guided occult lesion localization	In vivo: female adult rats	[28]
	Conjugation of a VCAM-1-binding peptide with a DOTA ring; development of a biotin/avidin three-step pretargeting system based on the same VCAM-1-binding peptide	68Ga	PET	Early diagnosis of atherosclerosis	In vitro: TNF-α activated HUVEC	[29,30]
	Conjugation of curcumin with a DOTA ring	68Ga	PET	Detection of colorectal cancer	In vitro: HT29 colorectal cancer cells In vivo: HT29 tumor-bearing mice	[31]
Nanoparticles	PAMAM dendrimer encapsulating sorafenib	FITC	Fluorescence optical imaging	Detection and treatment of liver cancer overexpressing ASGPR2	In vitro: HepG-2 human liver cancer cells	[32]
	PEG-decorated SLNs encapsulating Pt(IV)-prodrugs	Carbon dots	Fluorescence optical imaging	Assessment of BBB permeability	In vitro: hCMEC/D3 cells and polarized hCMEC/D3 endothelial cells seeded on a porous membrane (BBB model)	[33]
	PLGA-TSPO NPs	FITC	Fluorescence optical imaging	Subcellular targeting and imaging of TSPO-overexpressing cells	In vitro: rat C6 glioma cells	[34]
	TSPO-dextran nanogel	FITC	Fluorescence optical imaging	Subcellular targeting and imaging of TSPO-overexpressing cells	In vitro: rat C6 glioma cells	[35]
	PAMAM dendrimer	FITC	Fluorescence optical imaging	Detection of tumors or neurodegenerative diseases associated to TSPO overexpression	In vitro: C6 rat glioma cells	[36]
	Silica shell functionalized QDs	QDs	Fluorescence optical imaging	Detection of tumors or neurodegenerative diseases associated to TSPO overexpression	In vitro: C6 rat glioma cells	[37]
	USPIONs	Cyanine 5.5 fluorescent dye	NIR optical imaging	Detection of glioblastoma exploiting TSPO targeting	In vitro: U87-MG glioblastoma cells and PC3 prostate cancer cells In vivo: Balb/c athymic mice	[38]
	ECFC cells encapsulating AuNPs	AuNPs	PA imaging	Detection and treatment of cancer	In vitro: stack of chicken breast muscle Ex vivo: mouse melanoma, liver and spleen In vivo: CD1 immunodeficient mice	[39]
	Chitosan nanobubbles	Gd(III)-DOTP complex	MRI	Detection and treatment of cancer	In vitro: preliminary evaluation of US properties in agar gel suspension	[40]
	Fe-B NPs enveloped by polyvinylpyrrolidone	Iron	MRI	Optimization of NCT procedures for cancer treatment	In vitro: L929 fibroblasts, 4T1 mammary carcinoma cells and B16 melanoma cells In vivo: Balb/c mice	[41]
	Iron-doped hydroxyapatite NPs	Iron	MRI coupled to SPECT and/or PET	-	In vivo: C57BL/6 mice	[42]
	PLGA-PEG micelles encapsulating QDs	QDs	MRI	Detection of inflammatory bowel disease by MAdCAM-1 targeting	In vitro: SKBR3 cells In vivo: C57BL/6 mice	[43]
	Carboxymethylcellulose NPs	68Ga	PET	White blood cells imaging	In vitro: human leukocytes	[44]
	SiNPs	99mTc	SPECT	Detection of HER2-positive breast cancer	In vitro: SK-BR-3 cells Ex vivo, in vivo: SK-BR-3 tumor-bearing mice	[45,46]
	Fe3O4 NPs	Fe3O4 and 7-nitrobenzofurazan fluorescent dye	Optical imaging/MRI	Detection and treatment of cancer	In vitro: preliminary evaluation of fluorescence and MRI properties	[47]
	SiNPs embedding dye-modified Au NPs	IRDye 800CW and AuNPs	US/PA imaging	Detection and treatment of cancer	Ex vivo: chicken breast samples	[48]
	Au-Fe nanoalloys	Au and Fe	X-ray CT/MRI	-	In vivo: Balb/c mice	[22]