. 2022 Apr 19;27(9):2617. doi: 10.3390/molecules27092617

Table 7.

Formulation, indication, advantages and disadvantages of [^99mTc]Tc-PSMA RPs under clinical investigations.

Agent	Formulation/Radiosynthesis	Indication	Pros/Cons
^99mTc-TrofolastatConcluded Phase 3 (ClinicalTrials.gov Identifier: NCT02615067)	Two-vial kit formulation, the composition and the procedure were not deeply described. Labeling: 1° step NaTcO₄(40 mCi/1 mL saline) was added to the Isolink vial. Heat to 95 °C for 30 min. 2° Step: pH was adjusted to 7.5 with HCl.; PSMA-i (0.100 mg) was added. Heat to 95 °C for 30 min. Vol_tot= n.d RCY 85%. Purification: by HPLC RCP ≥ 98%. Specific activity: 37 TBq/mmol.	Useful to assist in the initial diagnosis of PCa, the monitoring of disease progression and the response to the therapeutic treatment by SPECT imaging.	Pros. Lower urinary excretion, which allows for detecting PCa in the pelvic area at early stages of the disease. Successfully detected very small PCa lesions (<10 mm) in bone, LNs, and prostate gland, thus suggesting that SPECT/CT scan with this agent may provide prognostic information for both primary tumor and biochemical recurrence. Detection rates (50%) slightly lower than that of ⁶⁸Ga-PSMA-11 at low PSA levels (0.2–1 ng/mL). Cons. Detection rates (50%) slightly lower than that of ⁶⁸Ga-PSMA-11 at low PSA levels (0.2–1 ng/mL).
^99m Tc-PSMA-I&S Phase2 (ClinicalTrials.gov Identifier: NCT04832958)	One vial: SnCl₂, tartrate, PB pH 8, PSMA-I&S (35–40 µg). Labeling: NaTcO₄ (20–30 mCi/1–5 mL), was added to the vial. pH 7.5–8, heat to 90 °C for 20 min. RCY 99%. Diluted to 10 mL. A_m44–52 GBq/µmol.	Useful to localize small metastases of PCa and to perform RGS with the main advantage of the immediate confirmation and removal of metastasis prior of the histological analysis. Superior substitute of ¹¹¹In PSMA-I&T.	Pros. Good visualization of the lesion also those previously identified with ⁶⁸Ga-PSMA11. High accumulations in LNs metastases, allowing for the exact intraoperative identification ad resection during RGS. Cons. Lesion-to-background contrast is achieved after 5 h p.i. Detection rates in patients with biochemical recurrence and low PSA levels (<4 ng/mL), are lower than that reported for ⁶⁸Ga-PSMA and for ^99mTc-Trofolastat.
^99m Tc-EDDA/HYNIC-PSMA Phase 1	Two-vial kit formulation. 1 lyophilized vial: SnCl₂ (0.020 mg), EDDA (20 mg), tricine (40.8 mg) mannitol (0.102 mg), HYNIC-PSMA-i (0.102 mg). 2° vial: Phosphate Buffer, 0.2 M pH 7. Labelling: to vial 1 was added PB (1 mL) and NaTcO₄ (20–30 mCi/1.0 mL). Heat to 95 °C for 10 min. RCY ≥ 98%.	Useful to assist in the initial diagnosis of PCa and the monitoring of disease progression. by SPECT imaging. Suitable in planning RGS or for identification of PSMA+ lesions before consideration of radioligand therapy, e.g., with ¹⁷⁷Lu-PSMA.	Pros. Faster blood clearance and urinary excretion, which allow the visualization, at 3 h p.i., of PCa in the pelvic area at early stage of diseases. Lower liver uptake and lowest effective radiation dose than ^99mTc-Trofolastat. Able to localize the lesions in bone, soft tissues and LN. Lesion detection rate of 78.3% with respect to Ga-68 PSMA. Cons. Lower sensitivity than ⁶⁸Ga-PSMA-11 for small-sized lesions. Only 28% of LNs lesions < 10 mm were detected, hence its use is not recommended in patients with small-volume disease.
^99m Tc- HYNIC-ALUG Phase 1	HYNIC-ALUG (0.010 mg), EDDA (0.5 mL of 20 mg/mL in 0.1 M NaOH solution), Tricine (0.5 mL of 40 mg/mL in PBS 0.2 M, pH = 6.0). NaTcO₄ (50 mCi/1.0 mL). SnCl₂ (50 μL of 1 mg/mL in 0.1 M HCl solution). Heat to 100 °C for 15 min. Vol_tot = 2.050 mL RCY ≥ 98%.	Useful to assist in the initial diagnosis of PCa and the monitoring of disease progression by SPECT imaging. This is also proposed for RGS.	Pros. Efficient detection of the metastasis at PSA level greater than 1.30 ng/mL Cons. The high accumulation in the kidneys makes difficult the interpretation of scintigraphic images.
^99m Tc- PSMA-T4 Phase 1	Sterile and apyrogenic freeze-dry kit: PSMA-T4 (20 mg), Tricine (50 mg), EDDA (5 mg), SnCl₂ (40 mg), Na₂HPO₄x12H₂O (29 mg),/NaH₂PO₄x2H₂O (3.0 mg). Labelling: NaTcO₄ (20–30 mCi/1.0–2.5 mL). Heat to 95 °C, 10 min. RCY ≥ 95%.	Useful to assist in the initial diagnosis of PCa and the monitoring of disease progression. Suitable for RGS and for identification/assessment of PSMA⁺ lesions before consideration of radioligand therapy.	Pros. RP is efficiently prepared in a short time by freeze-drying PSMA-T4 kit. Favorable distribution and kinetic behavior which allow the visualization of the PSMA + lesions within 3 h p.i. Cons. The high accumulation in the kidneys and renal excretion can cause difficulties in images interpretation.