Table 1.

Investigational PET/SPECT imaging in neuro-oncology

Biological target		Radiopharmaceuticals($)	Vector(ǂ)	References
Amino acid metabolism	C	[18F]F-ACBC [18F]F-tryptophan [18F]F-Glutamine [18F]F-FSPG [123I]iodo-IMT [123I]iodo-IPA	AA AA AA AA AA AA	49,51,311-317 318-323 324 325 326 326-328
	P	[18F]F-ELP [18F]F-AMPe [18F]F-A(M)Hep [11C]-/ [18F]F-tryptophan [18F]F-Glutamine [18F]F-IMP	AA AA AA AA AA AA	329,333 331 332 333-335 336,337 338
Angiogenesis (Integrin receptor family)	C	[18F]F-/ [68Ga]Ga-PRGD2	Pep	53,339-342
	P	[64Cu]Cu-PEG4-c(RGDyK) [68Ga]Ga-c(GDGEAyK) [111In]In-abegrin™ [99mTc]Tc-NC100692 [18F]F-fluciclatide [18F]F-PPRGD2 [18F]F-RGD-K5/ [68Ga]Ga-RGD [64Cu]Cu-c(RGDfK)]2 [64Cu]Cu-c(RGDfK)4 [64Cu]Cu-PEG4-E[PEG4-c(RGDfK)]2 [64Cu]Cu-Gly3-E[Gly3-c(RGDfK)]2 [18F]F-alfatide II	Pep Pep Ab Pep Pep Pep Pep Pep Pep Pep Pep Pep	343 344 345 346 347 348 349 350 54 351 351 352
Angiogenesis (Vascular endothelial growth factor receptor)	C	[123I]iodo-VEGF-165	Prot	353
	P	[111In]In-ZVEGFR2-Bp2 [89Zr]Zr-bevacizumab [64Cu]Cu-VEGF121 [64Cu]Cu-VEGF125-136 [111In]In-hnTf-VEGF	Abf Ab Prot Pep Pro	354 355 72,74 356 357
Epidermal growth factor receptor	C	[11C]-CPD153035	SM	358
	P	[124I]/ [131I]iodo-IPQA [11C]-/ [18F]F-ML01/-03/-04 [64Cu]Cu-/ [111In]In-cetuximab [111In]In-/ [125I]iodo-ch806 [18F]F-BEM-/ [68Ga]Ga-ZEGFR:1907 [89Zr]Zr-nimotuzumab [188Re]Re-U2 (ç) [18F]F-B-ME07 (°) [111In]In-hEGF	SM SM Ab Ab Abf Ab ON ON Ab	359 360 361,362 363,364 365 366 367 368 369
Chemokine receptor 4	C	[68Ga]Ga-pentixafor	Pep	94
	P	[11C]methyl-AMD3465	SM	370
Ephrin receptors	C	[89Zr]Zr-ifabotuzumab	Ab	371
	P	[64Cu]Cu-IIIA4 [64Cu]Cu-TNYL-RAW [64Cu]Cu-1C1	Ab Pep Ab	77 40 362
Hypoxia	C	[18F]F-DiFA [62Cu]/ [64Cu]Cu-ATSM [18F]F-EETNIM	SM SM SM	372 373-375 376
	P	[18F]F-RP170 [18F]F-HX4 [62Cu]/ [64Cu]Cu-ATSM	SM SM SM	377 378 55,67,75,379
Poly (ADP-ribose) polymerase	C	[18F]F-TT	SM	380
	P	[18F]F-/[123I]iodo-olaparib [123I]iodo-MAPi, [123I]/ [124I]/ [131I]iodo-2-PARPi [18F]F-PARPi-(FL)	SM SM SM SM	39,381 382 43 383
Glutamate Carboxypeptidase 2	C	[89Zr]Zr-IAB2M [18F]F-DCFPyL [68Ga]Ga-PSMA-617 [68Ga]Ga-PSMA-11 [18F]F-PSMA-1007	Abf Pep Pep Pep Pep	384 385 386 38,82,83,387-389 90
	P	[18F]F-DCFPyL [68Ga]Ga-PSMA-11	Pep Pep	91 91
Translocator protein (neuronal type) ($$)	C	[11C]-PK11195 [18F]F-GE-180 [123I]iodo-CLINDE	SM SM SM	390 38,85,391 392
	P	[18F]F-14 (£) [18F]F-VUIS1007 [18F]DPA-714 [18F]F-PBR06 [18F]F-VC701 [18F]F-AB5186	SM SM SM SM SM SM	393 394 395-499 400,401 402 403
Matrix-metalloproteinases	C	[131I]iodo-TM-601	SM	239,404
	P	[89Zr]Zr-LEM2/5 [18F]F-BR-351 [18F]F-P-chlorotoxin [18F]F-iCREKA [68Ga]Ga-/ [64Cu]Cu-MMP-14	Ab SM SM Pep Pep	405 399 406 407 408
Fibroblast activation protein	C	[68Ga]Ga-FAPI	SM	63,409,410
	P	[18F]F-SiFa(Glc)FAPI	SM	411
Lipid metabolism(++)	C	[11C]-/ [18F]F-(ethyl)choline [11C]-Acetate	SM SM	30-32,412,413 414,415
	P	[18F]-FPIA(*)	SM	416
Fibronectin (neuronal)	C	[123I]iodo-L19(scFv)2	Abf	417
	P	[18F]F-iCREKA	Pep	418
Apoptosis	C	[18F]F-ML10	SM	419,420
Sigma receptor	C	[18F]F-fluspidine (*)	SM	421-423
Somatostatin receptor 2	C	[68Ga]Ga-/ [111In]In-octreotide [68Ga]Ga-octreotide	Pep Pep	58,424 425,426
Deoxycytidine Kinase	C	[18F]F-clofarabine	SM	52,427
Neurokinin 1 receptor	C	[68Ga]Ga-Substance-P	Pep	93,105
Copper Transporter 1	P	[64Cu]Cu-(gold)nanocluster(+)	(**)	428
Carbonic Anhydrase IX	P	[18F]F-VM4-037	SM	429
Tenascin-C	P	[99mTc]Tc-TTA1 [18F]F-/ [64Cu]Cu-GBI-10	ON ON	430 431
Histone deacetylases	P	[18F]TFAHA 2-[18F]BzAHA	SM SM	432 433
Isocitrate Dehydrogenase 1	P	[18F]-triazine-diamine [18F]F-/ [131I]iodo-/ [125I]iodo-AGI5198 [18F]F-/ [ 125I]iodo-X (##) [11C]-Acetate	SM SM SM SM	434 435 436 437
Iron transport	P	[67Ga]/ [68Ga]Ga-citrate	SM	438
Glutathione transferase	P	[18F]F-BuEA-GS	SM	439,440
Hepatocyte growth factor receptor	P	[89Zr]Zr-/ [76Br]Br-onartuzumab [89Zr]Zr-rilotumumab [64Cu]Cu-rh-HGF	Ab Ab Pep	441 442 443
Mammalian target of rapamycin	P	[89Zr]Zr-transferrin	Prot	44,444
Tyrosine kinases	P	[18F]F-dasatinib [64Cu]Cu-vandetanib	SM SM	445 445
Myeloid cells	P	[89Zr]Zr-anti-CD11b	Ab	446
Platelet-derived growth factor receptor	P	[68Ga]Ga-/ [111In]In-ZO9591 [131I]iodo-/ [18F]F-imatinib [18F]F-dasatinib	Abf SM SM	369,447 448 445
Stem cells	P	[64Cu]Cu-AC133 [64Cu]Cu-/ [89Zr]Zr-YY146	Ab Ab	449 450,451

($) radiopharmaceutical are grouped as in preclinical (P) and clinical (C) stages of development; chelating agents for radiometal complexation were not denoted in the names to improve clarity of presentation; (++) Fatty acid synthesis (acetate) and choline metabolism for choline; pivalic acid undergoes intracellular metabolism via the fatty acid oxidation pathway (an berrant lipid metabolite detection), (£) no trivial name available- UPAC: 7-chloro-N,N,5-trimethyl-4-oxo-3(6-[¹⁸F]fluoropyridin-2-yl)-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide, (^##) no names given - a small library of nonradioactive analogs were designed and synthesized based on the chemical structure of reported butyl-phenyl sulfonamide enzyme inhibitors, (*) currently in clinical translation, (ç) DNA-based oligonucleotide (aptamer), (°) RNA based oligonucleotide (aptamer), (**) protein-mimic cluster, (+) dual-imaging modality - investigatory (proof-of-concept), (^$$) expressed on glioma-associated macrophages and microglia, ( ǂ ) vectors: amino-acid (AA), antibody (Ab), antibody fragment (Abf), small biomolecule (SM), peptide (Pep), protein (Prot), oligonucleotide (ON).