TABLE 2.

Probes Developed or Applied for Clinical and Preclinical Molecular Imaging of IBD

Imaging modality	Probea	Molecular process / Target	Information gained / Limitations	Species	Model	Ref
Confocal endo-microscopy	Fluorescein	Loss of tight junction between epithelial cells	Intestinal permeability	Human		32
Confocal endo-microscopy	Fluorescent adalumimabb	mTNF+ cells	Prediction of treatment response	Human		38,40
Chromo-endoscopy	Methylene blue Indigo carmineb	Difference in uptake between healthy and diseased mucosa	Intraepithelial neoplasia	Human		30
PET	18F-FDG	Glycolytic metabolism	Inflammation - False positive due to normal bowel activity Radiation exposure	Human		57
SPECT	99mTc-HMPAO-labeled leukocytes	Leukocytes	Inflammation – Tedious radiolabeling and high risk of cross contamination	Human		61–63
SPECT	111In-oxine labeled leukocytes	Leukocytes	Inflammation – High radiation dose, poor image quality	Human		58
SPECT	99mTc-CXCL8	Interleukin-8 receptors (CXCR1 and CXCR2)	Inflammation - Higher accuracy and sensitivity than endoscopy but lower specificity	Human		65
SPECT	99mTc/123I-IL2	Interleukin-2 receptors	Inflammation – Higher uptake could be a predictor of clinical relapse in patients with CD	Human		66,67
SPECT	99mTc-LeukoScan	Glycoproteins on granulocyte surface	Inflammation - Not suitable – Lower sensitivity and specificity than 99mTc-HMPAO-WBC	Human		64
Multiphoton micro-endoscopy	Second harmonic generationc	Collagen I	Epithelial crypt structure and underlying lamina of the colon mucosa. Changes in tissue morphology over time	Mice	DSS	43
Multiphoton micro-endoscopy	Autofluorescencec	NAHD FAD	Epithelial crypt structure and underlying lamina of the colon mucosa. Changes in tissue morphology over time	Mice	DSS	43
MRI	Gadofluorine-M	Nonspecific ECM protein binding	Discriminate between noninflamed, mildly inflamed, and severely inflamed colon wall	Rat	DNBS	85
MRI	Ultrasmall Iron Oxide SHU 555 C	Reticuloendothelial system (macrophages and dendritic cells)	Inflammation detection – Negative contrast agent	Rat	DNBS	84
MRI	Gd-DTPA	Nonspecific agent – Extracellular distribution	Similar and weak contrast enhancement in mild or severe colitis	Rat	DNBS	85
PET	64Cu-FIB504.64	⍺ 4β 7 and ⍺ Eβ 7 integrins	Inflammation - Long blood half-life and clearance	Mice	DSS	97
PET	64Cu-DAKT32	⍺ 4β 7 integrin	Not suitable for IBD imaging – weak signal in the bowel	Mice	DSS	96
PET	64Cu-FIB504.64-F(ab’)2	β 7 integrin	Inflammation - Fast clearance from nontarget tissues	Mice	DSS	96
PET	64Cu-FIB504.64-Fab	β 7 integrin	Inflammation - Fast clearance from nontarget tissues – Lower uptake in the inflamed tissue than 64Cu-FIB504.64-F(ab’)2	Mice	DSS	96
PET	89Zr-malDFO-GK1.5 cys-diabody	CD4+ T-cells	Inflammation – Probe uptake in the colon, ceca and mesenteric lymph nodes	Mice	DSS	98
PET	89Zr-lα-IL-1β	IL-1β cytokine	Strong correlation between disease severity and %ID/cc	Mice	DSS	99
PET	89Zr-α-CD11b	CD11b integrin	Not suitable for IBD – large uptake in many organs	Mice	DSS	99
PET	18F-DPA-714	Translocator Protein TSPO	Inflammation	Mice	DSS TNBS	102
SPECT	99mTc-scFv-VCAM-1	Vascular cell adhesion molecule-1 (VCAM-1)	High signal in the colon compared with controls and blocked	Rabbits	TNBS DSS	101
Optical imaging	MMP-activatable probe	MMP	Inflammation and colon cancer	Mice	Azoxymethane	88,92
Optical imaging	Cathepsin activatable probe	Cathepsin	Inflammation - Dysplasia Colitis-associated cancer	Mice	DSS IL-10 -/-	88–90
Optical imaging	NB200	Cathepsin S	Inflammation – Specificity tested ex vivo only	Mice	DSS	91
US	MB Selectin	E- and P-selectin	Inflammation	Mice	TNBS	93
US	MB P-selectin	P-selectin	Inflammation	Mice	TNBS	94

^aProbes are administered intravenously otherwise noted. _^bTopical administration. _^cNo dye administered. Abbreviation: DNBS, dinitrobenzene sulfonic acid.