Table 3.
Summary of the in vitro studies investigating α and β RIT approaches for the treatment of PDAC.
| Study/Objective | Target | RIC | Dissociation Constant ± SEM (nmol/L) | Cell Binding (%) | Survival Using RIC | Survival Using Non-Specific Control RIC | Apoptotic Cells Or γ-H2AX Foci (% ± SEM Where Available) |
|---|---|---|---|---|---|---|---|
| A-RIT Studies | |||||||
| Kasten et al. [46] Cell binding |
B7-H3 | 212Pb-376.96 | Adherent cells: 9.0 ± 1.1 CIC: 21.7 ± 0.7 |
Internalisation: Adherent cells: 44 CIC: 40 |
Measure: IC50 ± SEM Adherent cells: 41 ± 14 CIC: 26 ± 17 |
Measure: IC50 ± SEM Adherent cells: 120 ± 12 CIC cells: 180 ± 150 |
Not investigated |
| Qu et al. [37] In vitro cytotoxicity |
uPA/uPAR | 213Bi-PAI2 | Not investigated | Not investigated | Measure: activity for 37% cell survival (kBq) CFPAC-1: 133 CAPAN-1 185 PANC-1: 170 At 370 kBq: 5%–10% cell survival |
Measure: activity for 37% cell survival 2.2–2.7 MBq for all cell lines At 370 kBq: 90%–95% cell survival |
Measure: apoptotic cells At 24 h: CFPAC-1: 92 CAPAN-1: 87 PANC-1: 90 Control RIC: <5% |
| Qu et al. [47] In vitro cytotoxicity |
MUC1 | 213Bi-CHX.A”-C595 | Not investigated | Not investigated | Not investigated | Not investigated | Measure: apoptotic cells At 48 h: CAPAN: 73 ± 2.6 PANC-1: 78 ± 1.8 CFPAC-1: 81 ± 3.0 Control RIC: <12 ± 3.0 |
| Qu et al. [35] In vitro cytotoxicity |
MUC1 | 213Bi-cDTPA-C595 | Not investigated | Not investigated | Measure: activity for 37% cell survival (kBq) CAPAN-1: 167 CFPAC-1: 141 PANC-1: 159 At 370 kBq: 5%–10% cell survival |
Measure: activity for 37% cell survival (MBq) 2.2–2.6 for all cell lines At 370 kBq: 90–95% cell survival (control RIC) >95% cell survival (conjugated mAb or intact mAb only) |
Measure: Combined cell counts 4 h: 11 8 h: 18 12 h: 42 24 h: 87 48 h: 92 72 h: 81 Control RIC: <15% at all time points |
| B-RIT Studies | |||||||
| Sugyo et al. [48] Cell binding |
CD147 | 111In-059-053 (diagnostic agent to 90Y-059-053) | Intact 059-053: 0.35 CHX-A”-DTPA-059-053: 0.99 |
111In-059-053: 51 in BxPC-3 cells | Not investigated | Not investigated | Not investigated |
| Aghevlian et al. [49] In vitro cytotoxicity |
EGFR | 177Lu-MCP-panitumumab | Not investigated | RIC: 4.16 ± 0.17 RIC with excess mAB: 0.35 ± 0.01 Control RIC with excess mAB: 1.21 ± 0.18 |
Measure: clonogenic survival of treated cells compared to untreated controls 1.2 MBq RIC: 7.4-fold decrease 0.6 Mbq RIC: 9.0-fold decrease 0.3 MBq RIC: 1.9-fold decrease |
Not investigated | Measure: γ-H2AX foci 1.2 MBq RIC: 3.8-fold increase in density vs. untreated controls |
| Al-Ejeh et al. [6] In vitro cytotoxicity |
EGFR | 177Lu-anti-EGFR | Not investigated | Not investigated | Measure: clonogenic survival Triple combination therapy (RIT, Chk1i and gemcitabine) significantly reduced clonogenic survival vs. untreated controls |
Quantitative results not presented | Not investigated at an in vitro level |
| Sabbah et al. [30] Cell binding |
Ferritin | 111In- and 90Y-labelled Bz-DTPA-AMB8LK, Bz-CHX-AU-DTPA-AMB8LK and Bz-DOTA-AMB8LK. | Not investigated |
111In-DTPA-AMB8LK: 52 111In-CHX-A”-DTPA-AMB8LK: 43 111In-DOTA-AMB8LK: 24 |
Not investigated | Not investigated | Not investigated |
| Vervoort et al. [32] Cell binding |
Integrin avß5 |
125I-14C5, 111In-DOTA- 14C5 and 111In-DTPA-14C5 |
125I-14C5: 0.11 ± 0.01 111In-DTPA-14C5: 0.24 ± 0.02 111In-DOTA-14C5: 0.11 ± 0.03 Control RIC: no specific binding |
Internalisation at 24 h 125I-14C5: 6.93 ± 0.88 111In-DOTA- 14C5: 49.44 ± 0.75 111In-DTPA-14C5: 36.66 ± 1.42 |
Not investigated | Not investigated | Not investigated |
| Aung et al. [50] In vitro cytotoxicity |
Integrin α6β4 | 90Y-ITGA6B4 | Not investigated | Not investigated | Measure: colony formation at 24 h RIC and BEZ235: 90.9% reduction of PE vs. control RIC only: 52.5% reduction of PE vs. control |
Included in previous column | Measure: γ-H2AX positive cells (mean ± SD) at Day 3 RIC and BEZ235: 19.3 ± 7.0 RIC only: 12.7 ± 4.7 BEZ235 only: 4.0 ± 2.2 Control: 2.3 ± 1.2 |
| Sugyo et al. [51] Cell binding |
Transferrin | 111In-labelled TSP-A01, DOTA-TSP-A01, TSP-A02 and DOTA-TSP-A02 (diagnostic agents for 90Y-TSP-A01) |
111In-TSP-A01: 0.22 111In-DOTA-TSP-A01: 0.28 111In-TSP-A02: 0.17 111In-DOTA-TSP-A02: 0.22 |
Immunoreactive fraction: 111In-TSP-A01 and 111In-DOTA-TSP-A02: 1.0 | Not investigated | Not investigated | Not investigated |
RIC: radioimmunoconjugate, SEM: standard error measurement, CIC: cancer initiating cells, IC50: half maximal inhibitory concentration, mAb: monoclonal antibody, MCP: metal chelating polymer, Chk1i: checkpoint kinase 1 inhibitor, and PE: plating efficiency.