Tracers for non-invasive radionuclide imaging of immune checkpoint expression in cancer

Wierstra, Peter; Sandker, Gerwin; Aarntzen, Erik; Gotthardt, Martin; Adema, Gosse; Bussink, Johan; Raavé, René; Heskamp, Sandra

doi:10.1186/s41181-019-0078-z

EJNMMI Radiopharmacy and Chemistry

Table 1 Overview of nuclear imaging tracers for immune checkpoints. Only tracers that have been published and used in at least preclinical in vivo studies are described in the tables below

From: Tracers for non-invasive radionuclide imaging of immune checkpoint expression in cancer

Target	Name	Construct	Label	Timing	Tumor type /tissue	Therapeutic use	Reference
Clinicaly used
PD-1	⁸⁹Zr-Nivolumab	IgG	⁸⁹Zr	144 h	NSCLC	Yes	(Niemeijer et al. 2018)
PD-L1	⁸⁹Zr-Nivolumab	IgG	⁸⁹Zr	4 and 7 d	Bladder cancer, NSCLC, or TNBC	Yes	(Bensch et al. 2018)
PD-L1	¹⁸F-B MS-986192	Adnectin	¹⁸F	Dynamic PET immediately, static acquisition after 1 h	NSLC	No	(Niemeijer et al. 2018)
IDO/TDO	Alpha-[¹¹C]-methyll-tryptophan ([11C]AMT)	Small molecule	¹¹C	Dynamic scan initiate during tracer infusion, to 25 min p.i.	Glioblastoma, Gliomas, meningiomas, NSCLS, breast carcinomas, 3C prostate model	Yes	(Juhasz et al. 2006, 2009, 2012; Zitron et al. 2013; Michelhaugh et al. 2017; Guastella et al. 2016)
A2aR	[¹¹C]Preladenant	Small molecule	¹¹C	Dynamic scan initiate during tracer infusion, to 60 min p.i.	Cerebral A2aR imaging	Yes	(Zhou et al. 2017a, 2017b, 2017c, 2017d; Sakata et al. 2017; Ishibashi et al. 2018; Zhou et al. 2014)
A2aR	[¹¹C]TMSX	Small molecule	¹¹C	Dynamic scan initiate during tracer infusion	Cerebral A2aR imaging, Brown Fat	Yes	(Rissanen et al. 2013; Mishina et al. 2007, 2011; Naganawa et al. 2007, 2014; Lahesmaa et al. 2018; Rissanen et al. 2015)
Preclinically used
PD-1	⁶⁴Cu-anti-mouse- PD-1	IgG	⁶⁴Cu	1–48 h	B16-F10 melanoma	No	(Natarajan et al. 2017)
PD-1	⁸⁹Zr/⁶⁴Cu-pembrolizumab	IgG	⁸⁹Zr, ⁶⁴Cu	1–144 h	A375 melanoma with human peripheral blood mononuclear cells	No	(Natarajan et al. 2018a)
PD-1	⁶⁴Cu-pembrolizumab	IgG	⁶⁴Cu	1–48 h	293 T/hPD-1 and A375 melanoma with human peripheral blood mononuclear cells	No	(Hettich et al. 2016)
PD-1	⁶⁴Cu-anti-mouse PD-1	IgG	⁶⁴Cu	24 h	Naïve and PD-1^+/+ mice, B16-F10 melanoma	No	(England et al. 2017)
PD-1	⁸⁹Zr-pembrolizumab	IgG	⁸⁹Zr	0.5–168 h	Human PBMCs	No	(England et al. 2018)
PD-1	⁸⁹Zr-nivolumab	IgG	⁸⁹Zr	3–168 h	A549 human lung cancer	No	(Bensch et al. 2018)
PD-L1	C3, C7, E2 and E4	Nanobody	^99mTc	1 h	TC-1 myeloma	No	(Broos et al. 2017)
PD-L1	¹¹¹In-PD-L1.3.1	IgG	¹¹¹In	1–7 d	MDA-MB-231, SK-Br-3, SUM149, BT474, MCF-7	No	(Heskamp et al. 2015, 2019)
PD-L1	¹¹¹In-PD-L1-mAb	IgG	¹¹¹In	48–120 h	MDA-MB-231, SUM149, H2444, H1155	No	(Chatterjee et al. 2017)
PD-L1	WL12	Peptide	⁶⁴Cu	10 min-120 h	hPD-L1, CHO	No	(Chatterjee et al. 2017)
PD-L1	[¹⁸F]AlF-ZPD-L1_1	Affibody	¹⁸F	0 min	LOX, SUDHL6	No	(Gonzalez Trotter et al. 2017)
PD-L1	WL12	Peptide	⁶⁸Ga	60 min	hPD-L1, CHO	No	(De Silva et al. 2018)
PD-L1	¹⁸F-BMS-986192	Adnectin	¹⁸F	2 h	L2987, HT-29	Yes	(Donnelly et al. 2018)
PD-L1	α-PD-L1 (10F.9G2)	IgG	⁶⁴Cu	24 h	–	No	(England et al. 2017)
PD-L1	¹⁸F-B3	Single domain antibody (sdAb)	¹⁸F	–	–	No	(Ingram et al. 2017)
PD-L1	anti-PD-L1	IgG	¹¹¹In	1, 24 and 72 h	NT2.5	No	(Josefsson et al. 2016)
PD-L1	⁸⁹Zr anti-PD-L1	IgG	⁸⁹Zr	48 and 96 h	MEER, B16F10	No	(Kikuchi et al. 2017)
PD-L1	WL12	Peptide	⁶⁴Cu	2 h	H226, HCC827	No	(Kumar et al. 2019)
PD-L1	Atezolizumab	IgG	⁶⁴Cu	24 and 48 h	CHO-hPD-L1, MDA-MB-231, SUM149	Yes	(Lesniak et al. 2016)
PD-L1	⁸⁹Zr-Df-KN035	IgG	⁸⁹Zr	24 and 120 h	LN229	Yes	(Li et al. 2018)
PD-L1	High-affinity consensus (HAC) PD-1, and derivates	Peptide	⁶⁸Ga, ⁶⁴Cu	1 h	CT26 and CT26^PD-L1+	No	(Mayer et al. 2017)
PD-L1	Atezolizumab	IgG	⁸⁹Zr	2, 24,48, 72 and 96 h	B16F10	Yes	(Moroz et al. 2018)
PD-L1	C4	IgG	⁸⁹Zr	2, 24,48, 72 and 96 h	B16F10	No	(Natarajan et al. 2019)
PD-L1	FN3_hPD-L1	Adnectin	⁶⁴Cu	1–24 h	CT26, Raji, MDA-MB-231	No	(Nedrow et al. 2017a)
CTLA-4	Anti-mouse CTLA-4	IgG	⁶⁴Cu	48 h	CT26	No	(Higashikawa et al. 2014)
CTLA-4	Ipilimumab	IgG	⁶⁴Cu	48 h	A549 lung carcinoma xenograft	Yes	(Ehlerding et al. 2017, 2019)
CTLA-4	Ipilimumab-F (Ab’)₂	F (Ab’)₂	⁶⁴Cu	48 h	Activated human T cells	No	(Ehlerding et al. 2019)
CTLA-4	H11, H11-PEG20	VHH, PEGylated VHH	¹⁸F, ⁸⁹Zr	90 min and 24 h	B16F10	No	(Ingram et al. 2018)
CD80/ CD86	Belatacept	IgG1 Fc fused with CTLA-4 extracellular domain	¹¹¹In	18–48 h	Raji	Yes	(Meletta et al. 2016)
CD80	[¹¹C]AM7	Small molecule	¹¹C	1 min	APCs in human atherosclerotic plaques	No	(Meletta et al. 2017)
OX40	AbOX40	Antibody	⁶⁴Cu	2–9 days	A20	yes	(Alam et al. 2018)
IDO/TDO	[¹⁸F]IDO49	Small molecule	¹⁸F	Dynamic scan initiate during tracer infusion	HeLa xenografts	Yes	(Huang et al. 2017)
IDO/TDO	1-N-[¹¹C]-methyl-L- and -D-tryptophan ([¹¹C]-L-1MTrp and [¹¹C]-D-1MTrp)	Small molecule	¹¹C	Dynamic scan initiate during tracer infusion	–	Yes	(Xie et al. 2015)
IDO/TDO	L-5-[¹⁸F]fluoro-tryptophan and D-5-[¹⁸F]fluoro-tryptophan	Small molecule	¹⁸F	Dynamic scan initiate during tracer infusion	CT26, CT26-hIDO1, 17082A, 17095A	No	(Tang et al. 2017)
IDO/TDO	5-[¹⁸F]F-L-α-methyl tryptophan (5-[¹⁸F]F-AMT)	Small molecule	¹⁸F	30 min	B16F10	Yes	(Giglio et al. 2017)
IDO/TDO	1-(2-[18F]fluoroethyl)-l and d-tryptophan (1-L-[¹⁸F] FETrp and 1-D-[¹⁸F]FETrp)	Small molecule	¹⁸F	5 min, 2 h	Glioblastoma, NSCLC metastasis, breast cancer metastases, MDA-MB-231	Yes	(Michelhaugh et al. 2017; Xin and Cai 2017; Xin et al. 2019; Henrottin et al. 2016)
CD276	5573a	IgG	⁸⁹Zr	1–7 d	MDA-MB-231	Yes	(Burvenich et al. 2018)
A2aR	[¹⁸F]FESCH and [¹⁸F]FPSCH	Small molecule	¹⁸F	Dynamic scan initiate during tracer infusion	Cerebral A2aR imaging	Yes	(Khanapur et al. 2017)
A2aR	[¹¹C]KF17837	Small molecule	¹¹C	Dynamic scan initiate during tracer infusion	Cerebral A2aR imaging, Myocardium	Yes	(Noguchi et al. 1998; Ishiwata et al. 2000a, 1997, 2000c; Alam et al. 2018)
A2aR	[¹¹C]KF18446	Small molecule	¹¹C	Dynamic scan initiate during tracer infusion	Cerebral A2aR imaging	Yes	(Ishiwata et al. 2000a, 2002, 2000c)

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