In a recent study conducted by Blue Earth Therapeutics in collaboration with Minerva Imaging and others, the biodistribution and efficacy of a novel radio hybrid PSMA-targeting Lu-177 labeled compound, 177Lu-rhPSMA-10.1, was evaluated.  

In vivo biodistribution evaluation 

In non-tumor-bearing mice, 177Lu-rhPSMA-10.1 showed the highest uptake in the kidney, which cleared rapidly. A transient uptake was observed in the spleen, which cleared within 24 hours, whereas other organs showed no significant update. In a PSMA-expressing xenograft prostate cancer model 22Rv1, tumors exhibited the highest and sustained update. Among other organs, the kidneys initially had the highest uptake, which cleared quickly, and no significant accumulation was observed elsewhere. 

Moreover, 177Lu-rhPSMA-10.1 showed lower kidney retention at all time points examined while maintaining effective tumor targeting compared to the reference pharmaceutical, 177Lu-PSMA-I&T. Both agents cleared quickly from the blood, and only a transient uptake was observed in the spleen. 

In tumor-bearing mice, 177Lu-rhPSMA-10.1 demonstrated significantly lower kidney uptake and higher tumor accumulation than 177Lu-PSMA-I&T, resulting in a more favorable tumor-to-kidney ratio. Other organs showed minimal uptake for both agents. 

Efficacy in LNCaP and 22Rv1 tumor-bearing mice 

In the LNCaP xenograft–bearing mice, 177Lu-rhPSMA-10.1 significantly suppressed tumor growth at all evaluated doses (15, 30, and 45 MBq) from day 11 to day 28 in a dose-dependent manner (Figure 1A). Furthermore, 177Lu-rhPSMA-10.1 was well tolerated and no significant weight loss was observed in any treatment group throughout the study (Figure 1B-C).  

Figure 1: Therapeutic efficacy and tolerability of single administration of 177Lu-rhPSMA-10.1 (15, 30, and 45 MBq)

Figure 1: Therapeutic efficacy and tolerability of single administration of 177Lu-rhPSMA-10.1 (15, 30, and 45 MBq) in LNCaP tumor–bearing mice: relative tumor volume (A), survival (B), and relative body weight (C). From: Caroline Foxton et al., JNM 2025

In the 22Rv1 xenograft model, 177Lu-rhPSMA-10.1 significantly suppressed tumor growth from day 18 to day 35 compared to the vehicle group (Figure 2A). Treatment with 177Lu-PSMA-617 and 177Lu-PSMA-I&T resulted in significant suppression of tumor growth from days 18 to 35 and from day 25 to 35, respectively (Figure 2A). Compared to 177Lu-PSMA-I&T, 177Lu-rhPSMA-10.1 reduced tumor growth from days 39 to 49, whereas 177Lu-PSMA-617 was effective only on day 49.  

Median survival was 33.5 days for the vehicle group, 44 days for 177Lu-PSMA-I&T, and was not reached for 177Lu-rhPSMA-10.1 and 177Lu-PSMA-617. Survival was significantly improved upon 177Lu-rhPSMA-10.1 and 177Lu-PSMA-617 treatments. All treatments were well tolerated with no significant weight loss. 

Figure 2: Therapeutic efficacy and tolerability of single administration (30 MBq) of 177Lu-rhPSMA-10.1

Figure 2: Therapeutic efficacy and tolerability of single administration (30 MBq) of 177Lu-rhPSMA-10.1 in 22Rv1 tumor-bearing mice, compared with 177Lu-PSMA-617 and 177Lu-PSMA-I&T: relative tumor volume (A), survival (B), and relative body weight (C). From Caroline Foxton et al., JNM 2025

This study suggests that 177Lu-rhPSMA-10.1 is a promising next-generation radiopharmaceutical therapy. 

Interested in learning how Minerva Imaging can support biodistribution and efficacy studies of targeted radionuclide therapies in relevant PSMA-expressing or other xenograft models?  

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References: 

  • Caroline Foxton, Bradley Waldron, Rikke Veggerby Grønlund, Jaime (Jim) Simón, Bart Cornelissen, Edward O’Neill, Daniel Stevens. Preclinical Evaluation of 177Lu-rhPSMA-10.1, a Radiopharmaceutical for Prostate Cancer: Biodistribution and Therapeutic Efficacy. Journal of Nuclear Medicine Mar 2025, jnumed.124.268508; DOI: 10.2967/jnumed.124.268508