Table 1.

Summary of enhancing NET expression and ¹³¹I-mIBG efficacy in pre-clinical and clinical trials.

	Treatment	Preclinical data	Clincal data	References
Giving more 131I-mIBG	Escalating doses of 131I-mIBG	n/a	+	35
	Increasing cycles and/or cumulative doses of 131I-mIBG	n/a	+	21, 35–42
131I-mIBG as first-line therapy	131I-mIBG given in induction or consolidation +/− CT +/− ASCR	0	+	47–50
131I-mIBG (relapsed/refractory)	131I-mIBG + HDCT +/− ASCR	+	+	30, 33–35, 43–46
No-carrier added 131I-mIBG		+	=	20, 52–57
211At-mABG, 125I-mIBG		+	0	61, 64
Increasing NET expression	Cisplatin/Doxorubicin	+	+	48, 83–86
- Differentiating agents	Retinoic acid	+/−	0	73, 80, 81
	IFN alpha	+	0	73
	IFN gamma	+	0	71–73, 79, 81
- Modulating intracellular cascades	Protein Kinase C, CaMK	+	0	87, 88
- HDAC inhibitors		+	+	89, 90
- Corticosteroids		+	0	82
- Hyperthermia		−	−	12
Radiosensitization	HDAC inhibitors	+	+	89
	Proteasome inhibitors	+	0	91
	Topoisomerase inhibitors	+	P	92–94
	PARP inhibitors	+	0	95, 96
Ionizing radiation	External beam radiation	+	0	78, 100
Gene therapy		+	0	97–99
Hyperbaric O2		+	0	16

(+): increases NET expression/¹³¹I-mIBG efficacy, (−): ineffective, (=): no change in ¹³¹I-mIBG efficacy or NET, P: pending results, 0: no studies conducted, mIBG: meta-iodobenzylguanidine, mCi: milliCuries, kg: kilogram, ASCR: autologous stem cell rescue, CT: chemotherapy, HDCT: high-dose chemotherapy, NET: norepinephrine transporter, IFN: interferon, CaMK: calcium calmodulin dependent protein kinase, HDAC: histone deacetylase inhibitor, PARP: poly-(ADP-ribose) polymerase