Table 2.
Immuno-PET applications in PDAC.
| PET Imaging Probes | Conjugation Strategy | Targets | Hallmark | Models | References |
|---|---|---|---|---|---|
| [64Cu]Cu-DOTA-anti-PD-1 [64Cu]Cu-NOTA-anti-PD-1 [64Cu]Cu-NOTA-anti-PD-L1 |
Lysine-based random | PD-1/PD-L1 | Imaging of immune checkpoints | Orthotopic KRAS murine PDAC | [101] |
| [89Zr]Zr-Df-10D7 (anti-CDCP1 mAb) |
Lysine-based random | CUB Domain-Containing Protein 1 (CDCP1) | CDCP1 regulates migration, invasion, and extracellular matrix degradation | Patient-derived subcutaneous and orthotopic xenografts (PDX) mice | [102] |
| [64Cu]Cu-PCTA-cetuximab | Lysine-based random | Epidermal Growth Factor Receptor (EGFR) | EGFR is overexpressed in a wide variety of cancers | Resectable orthotopic xenograft mouse model with human PC XPA-1 cells | [103] |
|
[89Zr]Zr-Df-MVT-2163
(human HuMab-5B1 Ab) |
Lysine-based random | CA19-9 (Sialyl Lewis A) | CA19-9 is the most commonly used serum tumor marker for PDAC |
Patients with primary PDAC and metastases
(Phase 1) |
[104,105] |
| [64Cu]Cu-NOTA-NJB2 (nanobody) |
Sortase-Mediated Radiolabeling | Alternatively spliced EIIIB (EDB) domain of fibronectin tumor extracellular matrix and neovasculature | Fibronectin is a glycoprotein that forms a major constituent of tumor extracellular matrix and neovasculature | (K-rasLSL.G12D/+; p53R172H/+; PdxCre) KPC mouse models of PDAC | [106] |
| [89Zr]Zr-Df-LEM2/15 (anti-MM1-MMP mAb) |
Lysine-based random | MT1-MMP | Metalloprotease MT1-MMP is overexpressed in many tumors and associates with tumor growth, invasion, metastasis, and poor prognosis | Subcutaneous xenograft mouse model with Capan-2 cells, and subcutaneous and orthotopic PDX mice. | [107] |
| [89Zr]Zr-Df-MEHD7945A (duligotuzumab) |
Lysine-based random | EGFR and Receptor tyrosine-proteinase kinase erbB-3 (HER3) | EGFR and HER3 are highly expressed in PDAC, marking this aggressive disease with poor survival rates | Subcutaneous xenograft mouse model with AsPC-1 cells | [107] |
| [124I]-A2cDb (anti-PSCA 2B3 A2 cys-diabody) [124I]-A11 Mb (anti-PSCA minibody) |
Direct iodination | Prostate stem cell antigen (PSCA) | PSCA is also overexpressed in pancreatic carcinoma | Subcutaneous PDX mice | [108] |
| [64Cu]Cu-NOTA-3B4 (single chain Fv) |
Lysine-based random | Receptor for advanced glycation end products (RAGE) | RAGE is overexpressed in human pancreatic tumors; it is a critical promoter in the transition of premalignant epithelial precursors (PanIN) to PDAC | Balb c/nude mice bearing Panc02 tumors. No PET study, only ex vivo biodistribution. | [109] |
| [89Zr]Zr-Df-ALT-836 (anti-human TF mAb) |
Lysine-based random | Tissue factor (TF) | Overexpression of TF in pancreatic cancer has been correlated with high tumor grade, the primary disease’s extent, and local and distant metastatic invasion. | Subcutaneous xenograft mouse model with BxPC-3 or PANC-1 cells | [110] |
| [64Cu]Cu-NOTA-heterodimer-ZW800 (bispecific immunoconjugate of CD105 and TF Fab′ antibody fragments) |
Lysine-based random | Endoglobin (CD105) and TF | CD105 is a cell surface glycoprotein expressed on endothelial cells, and its overexpression in cancer has been linked to angiogenesis, metastasis, and cancer progression | Subcutaneous xenograft mouse model with BxPC-3 or PANC-1 cells | [111] |
| [89Zr]Zr-Df-5B1 (anti-CA19.9 mAb) |
Lysine-based random | CA19-9 | CA19-9 is the most commonly used serum tumor marker for PDAC | Orthotopic xenograft mouse model with CAPAN-2 cells | [112] |
| [89Zr]Zr-Df-1A2G11 (anti-IGF-1R mAb) |
Lysine-based random | Insulin-like growth factor-1 receptor (IGF-1R) | IGF-1R is a transmembrane receptor of the tyrosine kinase class involved in cell growth, apoptosis, and tumor invasion in cancer | Subcutaneous xenograft mouse model with MIA PaCa-2 or BxPC-3 cells | [112,113] |
| [64Cu]Cu-DOTA-MAb159 (anti-GRP78 mAb) |
Lysine-based random | Glucose-regulated protein (GRP78) | Cell-surface GRP78 expression, an immuno-globulin heavy-chain binding protein, has been detected in pancreatic cancer. | Subcutaneous xenograft mouse model with BxPC-3 cells | [114] |
| [64Cu]Cu-DOTA-11-25 (anti-Mesothelin mAb) |
Lysine-based random | Mesothelin (MSLN) | MSLN is a cell differentiation-associated glycoprotein, overexpressed in various cancers, including PDAC | Subcutaneous xenograft mouse model with CFPAC-1 or BxPC-3 cells | [115] |
| [89Zr]Zr-Df-TSP-A01 (anti-transferrin receptor mAb) |
Lysine-based random | Transferrin receptor (TfR) | TfR is upregulated on the cell surface of many cancer types, including pancreatic cancer | Subcutaneous xenograft mouse model with MIA PaCa-2 cells | [116] |
| [89Zr]Zr-Df-059-053 (human anti-CD147 mAb) |
Lysine-based random | CD147 | CD147 (so-called EMMPRIN) is a transmembrane protein of the immunoglobulin superfamily and is expressed in many types of tumors, including PDAC | Subcutaneous xenograft mouse model with MIA PaCa-2 cells | [117] |
| [64Cu]Cu-NOTA-panitumumab-F(ab′)2 | Lysine-based random | EGFR | EGFR is overexpressed in a wide variety of cancers | Subcutaneous xenograft mouse model with PANC-1 cells, and subcutaneous and orthotopic PDX OCIP23 mice | [118] |
| [89Zr]Zr-Df-5B1 (anti-CA19.9 mAb) |
Lysine-based random | CA19-9 | CA19-9 is the most commonly used serum tumor marker for PDAC | Subcutaneous xenograft mouse model with BxPC3 cells | [119] |
| [124I]-A2cDb (anti-CA19.9 diabody) |
Direct iodination | CA19-9 | CA19-9 is the most commonly used serum tumor marker for PDAC | Subcutaneous xenograft mouse model with BxPC3 or CAPAN-2 cells | [120] |
| [64Cu]Cu-NOTA-ALT-836 (anti-human TF mAb) |
Lysine-based random | Tissue factor (TF) | Overexpression of TF in pancreatic cancer has been correlated with high tumor grade, the primary disease’s extent, and local and distant metastatic invasion. | Subcutaneous xenograft mouse model with BxPC-3, PANC-1, or ASPC-1 cells | [121] |
| [64Cu]Cu-DOTA-2A3 (2A3 is an anti-CEACAM6 nanobody) [64Cu]Cu-DOTA-2A3-mFc (2A3 fused with a murine Fc fragment) [64Cu]Cu-DOTA-9A6 (anti-CEACAM6 murine mAb) |
Lysine-based random | Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM-6) | CEACAM-6 is a cell surface glycoprotein known to be highly expressed in most cancers | Subcutaneous xenograft mouse model with BxPC3 cells | [122] |
| [124I]-H310A (anti-CEA scFv-Fc) |
Direct iodination | Carcinoembryonic antigen (CEA) | CEA is a GPI-linked glycoprotein overexpressed in gastrointestinal epithelial tumors, including PDAC | Subcutaneous xenograft mouse model with BxPC-3, CAPAN-1, or HPAF-II cells | [121] |
Antibody-based PET imaging probes for PDAC ordered by the most recent publication date. Bioconjugation strategy has been categorized into three methods: lysine-based random, site-specific via sortase-mediated reaction, and direct iodination. Antibody-based PET imaging probes reaching clinical trials are highlighted in bold.