Although not always attainable in early clinical studies during development of new compounds for PRRT, a goal should be to determine Maximum Tolerated Dose (MTD in nmoles) of DOTA-peptide before saturating these receptors and subsequently MT Activty (MTA) of ¹⁷⁷Lu-DOTA-peptide at optimal mass of DOTA-peptide. Especially since success of PRRT depends on the availability of receptors so that required target uptake of activity and concordant therapeutic efficacy is achieved at optimal mass of DOTA-peptide.

Optimal mass is not always the lowest amount of mass, e.g. saturation of receptor-positive non targets, while on the other hand, the amount of mass is limited, that is before saturating the receptors available on the target lesions. Based on these data the radiochemical characteristics in terms of GBq and nmoles DOTA-peptide the formulation of the radiopharmaceutical can be designed. Moreover, pharmacokinetics, mode and frequency of administration, timing and dosage can also be optimized. In addition, from a dosimetric point-of-view for pretherapeutic measurements and PRRT the same amount of the same substance is recommended (1).

Although clinical dose-finding studies for PRRT are still scarce, there are PRRT protocols which increase activity at constant SA of ¹⁷⁷Lu-DOTA-peptides (here expressed in GBq per mass of DOTA-peptide), thus with concordant increase of DOTA-peptide.

Therefore we investigated maximal achievable SA of ¹⁷⁷Lu-DOTA-peptides (including DOTATOC, DOTATATE and DOTA-PSMA-617) labeled with ¹⁷⁷Lu, measuring incorporation of activity and radiochemical purity (RCP) as described (2). We found SA of ¹⁷⁷Lu from enriched ¹⁷⁶Lu was always higher as stated by vendors, and maximal achievable SA of concordant ¹⁷⁷Lu-DOTA-peptides were also higher. Even at a mol/mol ratio of ≥ 1.1 (DOTA-peptide vs. Lu) resulted in successful labeling: ≥99% incorporation of ¹⁷⁷Lu.

We conclude that when increasing the activity (in GBq) the SA of ¹⁷⁷Lu-DOTA-peptides should be increased, preferably at constant optimal mass of DOTA-peptide.