Among other factors, success of PRRT depends on the availability of ¹⁷⁷Lu-DOTA-peptides at adequately high SA, so that required target uptake of activity and concordant therapeutic efficacy can be achieved before saturating the receptors available on the target lesions. This directly depends on the SA of ¹⁷⁷Lu (expressed in activity per mass of Lu).

Clinical dose-finding studies for PRRT are scarce, and to our knowledge, no clinical dose-finding data on activity or mass, or Maximal Tolerated Activity (MTA) or MT Dose are published on PRRT with ¹⁷⁷Lu-PSMA. PRRT of metastatic Prostate Cancer is currently performed with a typical formulation of 4 GBq ¹⁷⁷Lu-DOTA-PSMA-617 (0.1 mg) at medium SA (here expressed in GBq per mass of DOTA-PSMA-617, MW=1042 g/mol). Moreover, from a dosimetric point-of-view pretherapeutic measurements and PRRT with the same amount of the same substance is recommended (Kletting et al., 2012,2016).

Therefore we investigated this typical formulation (4 GBq ¹⁷⁷Lu-DOTA-PSMA-617 (0.1 mg)) at various SA of ¹⁷⁷Lu (range 400-1500 GBq ¹⁷⁷Lu per mg Lu).

We found that 0.1 µmoles DOTA-PSMA-617 can successfully be labeled with 4 GBq ¹⁷⁷Lu at SA of ≥ 400 GBq ¹⁷⁷Lu per mg. This equals a mol/mol ratio of DOTA-peptide over Lu of 3. The mol/mol ratio will further increase concordant with higher SA of ¹⁷⁷Lu, all at full incorporation of ¹⁷⁷Lu. In addition, even 7 GBq ¹⁷⁷Lu (at SA ≥ 400 GBq ¹⁷⁷Lu per mg) is successfully incorporated with preferred constant mass of 0.1 µmoles DOTA-PSMA-617.

These data confirm our earlier ¹⁷⁷Lu labeling studies with other DOTA-peptides.