The antitumor effects of [177Lu]Lu-DPI-4452 were assessed in HT-29 and SK-RC-52 xenografts. Tumor-bearing mice were randomized into 4 groups and injected with single doses of vehicle, 100 or 33 MBq of [177Lu]Lu-DPI-4452, or 3 once-weekly 33-MBq doses of [177Lu]Lu-DPI-4452. Treatment was well tolerated, including no significant changes in kidney function biomarkers (Supplemental Figs. 911). All treatment groups, except HT-29 xenograft-bearing mice receiving a single dose of 33 MBq, had significantly reduced tumor volumes compared with vehicle controls by day 16 (HT-29) or day 13 (SK-RC-52). Both 100-MBq and 3 once-weekly 33-MBq doses produced maximal tumor growth inhibition at day 23 for HT-29 xenografts and day 36 for SK-RC-52 xenografts, although 3 once-weekly 33-MBq doses produced a more sustained effect than a single 100-MBq dose in both models. No significant difference in tumor size for SK-RC-52 xenografts was observed at day 36 after treatment with single 100- or 33-MBq doses of [177Lu]Lu-DPI-4452 (Supplemental Table 4). These findings were consistent with the improved survival seen in treated mice compared with control mice (Supplemental Fig. 14; Supplemental Table 5). SPECT/CT analysis of 3 mice with xenografts per treatment arm revealed high tumor uptake in both models that was not modulated by repeated [177Lu]Lu-DPI-4452 treatments. Similar radioactivity was found in SK-RC-52 tumors for all doses, suggesting that uptake was already maximal at the lowest dose of 33 MBq. These findings demonstrated a strong antitumor effect of [177Lu]Lu-DPI-4452 on CAIX-expressing tumors and suggested dose fractionation may be beneficial.

The antitumor effects of [177Lu]Lu-DPI-4452 were assessed in HT-29 and SK-RC-52 xenografts. Tumor-bearing mice were randomized into 4 groups and injected with single doses of vehicle, 100 or 33 MBq of [177Lu]Lu-DPI-4452, or 3 once-weekly 33-MBq doses of [177Lu]Lu-DPI-4452. Treatment was well tolerated, including no significant changes in kidney function biomarkers (Supplemental Figs. 911). All treatment groups, except HT-29 xenograft-bearing mice receiving a single dose of 33 MBq, had significantly reduced tumor volumes compared with vehicle controls by day 16 (HT-29) or day 13 (SK-RC-52). Both 100-MBq and 3 once-weekly 33-MBq doses produced maximal tumor growth inhibition at day 23 for HT-29 xenografts and day 36 for SK-RC-52 xenografts, although 3 once-weekly 33-MBq doses produced a more sustained effect than a single 100-MBq dose in both models. No significant difference in tumor size for SK-RC-52 xenografts was observed at day 36 after treatment with single 100- or 33-MBq doses of [177Lu]Lu-DPI-4452 (Supplemental Table 4). These findings were consistent with the improved survival seen in treated mice compared with control mice (Supplemental Fig. 14; Supplemental Table 5). SPECT/CT analysis of 3 mice with xenografts per treatment arm revealed high tumor uptake in both models that was not modulated by repeated [177Lu]Lu-DPI-4452 treatments. Similar radioactivity was found in SK-RC-52 tumors for all doses, suggesting that uptake was already maximal at the lowest dose of 33 MBq. These findings demonstrated a strong antitumor effect of [177Lu]Lu-DPI-4452 on CAIX-expressing tumors and suggested dose fractionation may be beneficial.

The antitumor effects of [177Lu]Lu-DPI-4452 were assessed in HT-29 and SK-RC-52 xenografts. Tumor-bearing mice were randomized into 4 groups and injected with single doses of vehicle, 100 or 33 MBq of [177Lu]Lu-DPI-4452, or 3 once-weekly 33-MBq doses of [177Lu]Lu-DPI-4452. Treatment was well tolerated, including no significant changes in kidney function biomarkers (Supplemental Figs. 911). All treatment groups, except HT-29 xenograft-bearing mice receiving a single dose of 33 MBq, had significantly reduced tumor volumes compared with vehicle controls by day 16 (HT-29) or day 13 (SK-RC-52). Both 100-MBq and 3 once-weekly 33-MBq doses produced maximal tumor growth inhibition at day 23 for HT-29 xenografts and day 36 for SK-RC-52 xenografts, although 3 once-weekly 33-MBq doses produced a more sustained effect than a single 100-MBq dose in both models. No significant difference in tumor size for SK-RC-52 xenografts was observed at day 36 after treatment with single 100- or 33-MBq doses of [177Lu]Lu-DPI-4452 (Supplemental Table 4). These findings were consistent with the improved survival seen in treated mice compared with control mice (Supplemental Fig. 14; Supplemental Table 5). SPECT/CT analysis of 3 mice with xenografts per treatment arm revealed high tumor uptake in both models that was not modulated by repeated [177Lu]Lu-DPI-4452 treatments. Similar radioactivity was found in SK-RC-52 tumors for all doses, suggesting that uptake was already maximal at the lowest dose of 33 MBq. These findings demonstrated a strong antitumor effect of [177Lu]Lu-DPI-4452 on CAIX-expressing tumors and suggested dose fractionation may be beneficial.

The antitumor effects of [177Lu]Lu-DPI-4452 were assessed in HT-29 and SK-RC-52 xenografts. Tumor-bearing mice were randomized into 4 groups and injected with single doses of vehicle, 100 or 33 MBq of [177Lu]Lu-DPI-4452, or 3 once-weekly 33-MBq doses of [177Lu]Lu-DPI-4452. Treatment was well tolerated, including no significant changes in kidney function biomarkers (Supplemental Figs. 911). All treatment groups, except HT-29 xenograft-bearing mice receiving a single dose of 33 MBq, had significantly reduced tumor volumes compared with vehicle controls by day 16 (HT-29) or day 13 (SK-RC-52). Both 100-MBq and 3 once-weekly 33-MBq doses produced maximal tumor growth inhibition at day 23 for HT-29 xenografts and day 36 for SK-RC-52 xenografts, although 3 once-weekly 33-MBq doses produced a more sustained effect than a single 100-MBq dose in both models. No significant difference in tumor size for SK-RC-52 xenografts was observed at day 36 after treatment with single 100- or 33-MBq doses of [177Lu]Lu-DPI-4452 (Supplemental Table 4). These findings were consistent with the improved survival seen in treated mice compared with control mice (Supplemental Fig. 14; Supplemental Table 5). SPECT/CT analysis of 3 mice with xenografts per treatment arm revealed high tumor uptake in both models that was not modulated by repeated [177Lu]Lu-DPI-4452 treatments. Similar radioactivity was found in SK-RC-52 tumors for all doses, suggesting that uptake was already maximal at the lowest dose of 33 MBq. These findings demonstrated a strong antitumor effect of [177Lu]Lu-DPI-4452 on CAIX-expressing tumors and suggested dose fractionation may be beneficial.

The antitumor effects of [177Lu]Lu-DPI-4452 were assessed in HT-29 and SK-RC-52 xenografts. Tumor-bearing mice were randomized into 4 groups and injected with single doses of vehicle, 100 or 33 MBq of [177Lu]Lu-DPI-4452, or 3 once-weekly 33-MBq doses of [177Lu]Lu-DPI-4452. Treatment was well tolerated, including no significant changes in kidney function biomarkers (Supplemental Figs. 911). All treatment groups, except HT-29 xenograft-bearing mice receiving a single dose of 33 MBq, had significantly reduced tumor volumes compared with vehicle controls by day 16 (HT-29) or day 13 (SK-RC-52). Both 100-MBq and 3 once-weekly 33-MBq doses produced maximal tumor growth inhibition at day 23 for HT-29 xenografts and day 36 for SK-RC-52 xenografts, although 3 once-weekly 33-MBq doses produced a more sustained effect than a single 100-MBq dose in both models. No significant difference in tumor size for SK-RC-52 xenografts was observed at day 36 after treatment with single 100- or 33-MBq doses of [177Lu]Lu-DPI-4452 (Supplemental Table 4). These findings were consistent with the improved survival seen in treated mice compared with control mice (Supplemental Fig. 14; Supplemental Table 5). SPECT/CT analysis of 3 mice with xenografts per treatment arm revealed high tumor uptake in both models that was not modulated by repeated [177Lu]Lu-DPI-4452 treatments. Similar radioactivity was found in SK-RC-52 tumors for all doses, suggesting that uptake was already maximal at the lowest dose of 33 MBq. These findings demonstrated a strong antitumor effect of [177Lu]Lu-DPI-4452 on CAIX-expressing tumors and suggested dose fractionation may be beneficial.

The antitumor effects of [177Lu]Lu-DPI-4452 were assessed in HT-29 and SK-RC-52 xenografts. Tumor-bearing mice were randomized into 4 groups and injected with single doses of vehicle, 100 or 33 MBq of [177Lu]Lu-DPI-4452, or 3 once-weekly 33-MBq doses of [177Lu]Lu-DPI-4452. Treatment was well tolerated, including no significant changes in kidney function biomarkers (Supplemental Figs. 911). All treatment groups, except HT-29 xenograft-bearing mice receiving a single dose of 33 MBq, had significantly reduced tumor volumes compared with vehicle controls by day 16 (HT-29) or day 13 (SK-RC-52). Both 100-MBq and 3 once-weekly 33-MBq doses produced maximal tumor growth inhibition at day 23 for HT-29 xenografts and day 36 for SK-RC-52 xenografts, although 3 once-weekly 33-MBq doses produced a more sustained effect than a single 100-MBq dose in both models. No significant difference in tumor size for SK-RC-52 xenografts was observed at day 36 after treatment with single 100- or 33-MBq doses of [177Lu]Lu-DPI-4452 (Supplemental Table 4). These findings were consistent with the improved survival seen in treated mice compared with control mice (Supplemental Fig. 14; Supplemental Table 5). SPECT/CT analysis of 3 mice with xenografts per treatment arm revealed high tumor uptake in both models that was not modulated by repeated [177Lu]Lu-DPI-4452 treatments. Similar radioactivity was found in SK-RC-52 tumors for all doses, suggesting that uptake was already maximal at the lowest dose of 33 MBq. These findings demonstrated a strong antitumor effect of [177Lu]Lu-DPI-4452 on CAIX-expressing tumors and suggested dose fractionation may be beneficial.