Table 1.
Overview of PSMA ligands for intraoperative PCa detection
| Reference | Year | PSMA ligand | Radio-nuclide | Fluoro-phore* | Research status | Main results | ||
|---|---|---|---|---|---|---|---|---|
| Radioguided surgery | ||||||||
| Maurer et al. 35 | 2015 | lysine-urea-glutamate | 111In (γ) | - | Clinical feasibility, 5 patients | - Identification of additional positive lesions not detected during preoperative PET/CT imaging | ||
| Schottelius et al. 22 | 2015 | lysine-urea-glutamate | 111In (γ) | - | Exemplary patient | - Radioguided resection of PSMA-positive lesions | ||
| Robu et al. 21 | 2017 | lysine-urea-glutamate | 99mTc (γ) | - | Two exemplary patients | - Successful detection and resection of radiosignal-positive lesions | ||
| Maurer et al. 23 | 2018 | lysine-urea-glutamate | 99mTc (γ) | - | Retrospective analysis, 31 patients | - Comparison of radioactive rating with histopathological analysis; specificity 93%, sensitivity 83.6% | ||
| Rauscher et al. 36 | 2017 | lysine-urea-glutamate | 111In (γ) + 99mTc (γ) | - | Clinical follow up, 55 patients |
- PSA level reduction > 50% in 44 (80%), > 90% in 29 (53%) patients | ||
| Horn et al. 24 | 2017 | lysine-urea-glutamate | 111In (γ) + 99mTc (γ) | - | Clinical follow up, 59 patients |
- PSA < 0.2 ng/mL in 67% of patients | ||
| Fluorescence-guided surgery | ||||||||
| Humblet et al. 43 | 2005 | GPI | - | IRDye78 (771-796 nm) | Preclinical, s.c. LNCaP | - NIR fluorophore conjugation improved PSMA-affinity over 20-fold | ||
| Wang et al. 44 | 2014 | PSMA-1 | - | IRDye800CW (778-794 nm) + Cy5.5 (675-694 nm) | Preclinical, orthotopic PC3-PIP | - Pharmacokinetics highly dependent on the conjugated fluorophore | ||
| Bao et al. 34 | 2017 | lysine-urea-glutamate | - | Cy5.5 (675-694 nm), Cy7 (753-775 nm) + ZW800+3C (774-789 nm) | Preclinical, s.c. LNCaP | - Physicochemical properties of fluorophores drastically alter characteristics of ligands | ||
| Kularatne et al. 51 | 2018 | DUPA | - | S0456 (788-800 nm) | Preclinical, s.c./orthotopic 22Rv1/LNCaP | - Sub-nanomolar concentration sufficient to visualize small lesions. - Retention of fluorescent signal in PSMA+ tumors > 48 hours |
||
| Kelderhouse et al. 52 | 2013 | DUPA | - | AF647 (650-665 nm), Dylight680 (692-712 nm) + IRDye-800CW (778-794 nm) | Preclinical, intracardial injections 22Rv1 |
- Complete resection of metastasis with minimal contamination from healthy tissue | ||
| Kovar et al. 1 | 2014 | YC-27 | - | IRDye-800CW (778-794 nm) | Preclinical, s.c. 22Rv1 | - High tissue contrast and sufficient tumor delineation at doses as low as 0.25 nmol | ||
| Neuman et al. 53 | 2015 | YC-27 | - | IRDye-800CW (778-794 nm) | Preclinical, s.c. PC3-PIP | - 0% recurrences when resected with NIRF-guidance compared to 40% in control white-light mice | ||
| Multimodal-guided surgery | ||||||||
| Banerjee et al.58 | 2011 | lysine-urea-glutamate | 111In (γ) | IRDye-800CW (778-794 nm) | Preclinical, s.c. PC3-PIP | - Multimodal visualization, delineation and high uptake of the tracer, 16.4±3.7 %ID/g** | ||
| Baranski et al. 54 | 2017 | PSMA-11 | 68Ga (β+) | IRDye-800CW (778-794 nm)+ Dylight800 (777-794 nm) | Preclinical, s.c. LNCaP + healthy pigs |
- Conjugation of IRDye800CW (13.6 ± 3.7 %ID/g) and DyLight800 (15.6 ± 5.5 %ID/g) increased specific tumor uptake** - Ligands enabled radical prostatectomy under fluorescence-guidance in pigs |
||
| Schottelius et al. 59 | 2018 | lysine-urea-glutamate | 68Ga (β+) | Sulfo‐Cy5 (646-662 nm) | Precinical, s.c. LNCaP |
- PSMA-specific uptake in tumor (4.5 ± 1.8 %ID/g)** - Tumor/background ratios at 1 h p.i. of 2.1 and 9.6 for blood and muscle. |
||
* Fluorescent wavelengths are indicated as excitation maximum-emission maximum in nm.** Note that PSMA expression levels differ between tumor models used. Therefore, uptake values (%ID/g) cannot be directly compared. Abbreviations: p.i.; post injection, s.c.; subcutaneous, PSMA; Prostate specific membrane antigen, h; hours, %ID/g; Percentage injected dose per gram, NIRF; Near-infrared fluorescence.