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.

After [68Ga]Ga-DPI-4452 administration, high tumor-specific uptake was observed as early as 15min and was sustained for all time points assessed. One hour was chosen as the optimal time point on the basis of central reader visual assessment of image quality, visualization of all lesions, and heterogeneity in tumor uptake. Among all lesions, 17 metastases in bone, lymph nodes, lungs, pancreas, and parotid glands were not readily identifiable by conventional imaging. Low renal parenchymal uptake enabled identification of renal tumors. SUVmax 1h after administration across 36 lesions ranged from 6.8 to 211.6 (mean, 64.6 [SD, 54.8]). In patients 1, 2, and 3, the highest SUVmax was 109, 106, and 212, respectively, whereas the highest SUVmean was 39, 62, and 89, respectively.

After [68Ga]Ga-DPI-4452 administration, high tumor-specific uptake was observed as early as 15min and was sustained for all time points assessed. One hour was chosen as the optimal time point on the basis of central reader visual assessment of image quality, visualization of all lesions, and heterogeneity in tumor uptake. Among all lesions, 17 metastases in bone, lymph nodes, lungs, pancreas, and parotid glands were not readily identifiable by conventional imaging. Low renal parenchymal uptake enabled identification of renal tumors. SUVmax 1h after administration across 36 lesions ranged from 6.8 to 211.6 (mean, 64.6 [SD, 54.8]). In patients 1, 2, and 3, the highest SUVmax was 109, 106, and 212, respectively, whereas the highest SUVmean was 39, 62, and 89, respectively.

After [68Ga]Ga-DPI-4452 administration, high tumor-specific uptake was observed as early as 15min and was sustained for all time points assessed. One hour was chosen as the optimal time point on the basis of central reader visual assessment of image quality, visualization of all lesions, and heterogeneity in tumor uptake. Among all lesions, 17 metastases in bone, lymph nodes, lungs, pancreas, and parotid glands were not readily identifiable by conventional imaging. Low renal parenchymal uptake enabled identification of renal tumors. SUVmax 1h after administration across 36 lesions ranged from 6.8 to 211.6 (mean, 64.6 [SD, 54.8]). In patients 1, 2, and 3, the highest SUVmax was 109, 106, and 212, respectively, whereas the highest SUVmean was 39, 62, and 89, respectively.

After [68Ga]Ga-DPI-4452 administration, high tumor-specific uptake was observed as early as 15min and was sustained for all time points assessed. One hour was chosen as the optimal time point on the basis of central reader visual assessment of image quality, visualization of all lesions, and heterogeneity in tumor uptake. Among all lesions, 17 metastases in bone, lymph nodes, lungs, pancreas, and parotid glands were not readily identifiable by conventional imaging. Low renal parenchymal uptake enabled identification of renal tumors. SUVmax 1h after administration across 36 lesions ranged from 6.8 to 211.6 (mean, 64.6 [SD, 54.8]). In patients 1, 2, and 3, the highest SUVmax was 109, 106, and 212, respectively, whereas the highest SUVmean was 39, 62, and 89, respectively.

After [68Ga]Ga-DPI-4452 administration, high tumor-specific uptake was observed as early as 15min and was sustained for all time points assessed. One hour was chosen as the optimal time point on the basis of central reader visual assessment of image quality, visualization of all lesions, and heterogeneity in tumor uptake. Among all lesions, 17 metastases in bone, lymph nodes, lungs, pancreas, and parotid glands were not readily identifiable by conventional imaging. Low renal parenchymal uptake enabled identification of renal tumors. SUVmax 1h after administration across 36 lesions ranged from 6.8 to 211.6 (mean, 64.6 [SD, 54.8]). In patients 1, 2, and 3, the highest SUVmax was 109, 106, and 212, respectively, whereas the highest SUVmean was 39, 62, and 89, respectively.

After [68Ga]Ga-DPI-4452 administration, high tumor-specific uptake was observed as early as 15min and was sustained for all time points assessed. One hour was chosen as the optimal time point on the basis of central reader visual assessment of image quality, visualization of all lesions, and heterogeneity in tumor uptake. Among all lesions, 17 metastases in bone, lymph nodes, lungs, pancreas, and parotid glands were not readily identifiable by conventional imaging. Low renal parenchymal uptake enabled identification of renal tumors. SUVmax 1h after administration across 36 lesions ranged from 6.8 to 211.6 (mean, 64.6 [SD, 54.8]). In patients 1, 2, and 3, the highest SUVmax was 109, 106, and 212, respectively, whereas the highest SUVmean was 39, 62, and 89, respectively.