Formulation and clinical translation of [177Lu]Lu-trastuzumab for radioimmunotheranostics of metastatic breast cancer.
ABSTRACT: Trastuzumab (Herceptin®) is an approved immunotherapeutic agent used for the treatment of metastatic breast cancer over-expressing HER2 antigen receptors. The aim of the present work is to standardize the formulation protocol of [177Lu]Lu-trastuzumab addressing various reaction parameters, evaluating the efficacy of the radiolabeled product by in vitro investigations, scaling-up the preparation for administration in patients and performing preliminary clinical studies in patients suffering from metastatic breast cancer. Trastuzumab was conjugated with a suitable bi-functional chelating agent namely, p-NCS-benzyl-DOTA. On average 6.15 ± 0.92 p-NCS-benzyl-DOTA molecules were observed to be attached to each trastuzumab moiety. [177Lu]Lu-trastuzumab could be prepared with >95% radiochemical purity (% RCP) employing the optimized radiolabeling procedure. In vitro studies revealed the affinity of [177Lu]Lu-trastuzumab towards HER2 +ve cancer cell lines as well as against HER2 protein (Kd = 13.61 nM and 11.36 nM, respectively). The value for percentage immunoreactive fraction (% IRF) for [177Lu]Lu-trastuzumab was observed to be 76.92 ± 2.80. Bio-distribution studies in Swiss mice revealed non-specific uptake in the blood, liver, lungs and heart followed by gradual clearance of activity predominantly through the hepatobiliary route. Preliminary clinical studies carried out in 8 cancer patients with immunohistochemically proven HER2 positive metastatic breast cancer revealed preferential localization of [177Lu]Lu-trastuzumab in breast cancer lesions, which was in concordance with [18F]FDG-PET scans recorded earlier in the same patient indicating the potential of the agent towards radioimmunotheranostic applications.
Project description:We report a practical and high-yield synthesis of a bimodal bifunctional ligand 3p-C-NETA-NCS containing the isothiocyanate group for conjugation to a tumor targeting antibody. 3p-C-NETA-NCS was conjugated to a tumor-targeting antibody, trastuzumab, and the corresponding 3p-C-NETA-trastuzumab conjugate was evaluated and compared to trastuzumab conjugates of the known bifunctional ligands C-DOTA, C-DTPA, and 3p-C-DEPA for radiolabeling kinetics with (90)Y and (177)Lu. 3p-C-NETA-trastuzumab conjugate exhibited extremely rapid complexation kinetics with (90)Y and (177)Lu. (90)Y-3p-C-NETA-trastuzumab and (177)Lu-3p-C-NETA-trastuzumab conjugates were stable in human serum for 2 weeks. A pilot biodistribution study was conducted to evaluate in vivo stability and tumor targeting of (177)Lu-radiolabeled trastuzumab conjugate using nude mice bearing ZR-75-1 human breast cancer. (177)Lu-3p-C-NETA-trastuzumab conjugate displayed low radioactivity level at blood (1.6%), low organ uptake (<2.2%), and high tumor-to-blood ratio (6.4) at 120 h. 3p-C-NETA possesses favorable in vitro and in vivo profiles and is an excellent bifunctional chelator that can be used for targeted RIT applications using (90)Y and (177)Lu and has the potential to replace DOTA and DTPA analogues in current clinical use.
Project description:<h4>Background</h4>Epidermal growth factor receptors (EGFR) are overexpressed on many head and neck squamous cell carcinoma (HNSCC). Radioimmunotherapy (RIT) with F(ab')<sub>2</sub> of the anti-EGFR monoclonal antibody panitumumab labeled with the β-particle emitter, <sup>177</sup>Lu may be a promising treatment for HNSCC. Our aim was to assess the feasibility of a theranostic strategy that combines positron emission tomography (PET) with [<sup>64</sup>Cu]Cu-DOTA-panitumumab F(ab')<sub>2</sub> to image HNSCC and predict the radiation equivalent doses to the tumour and normal organs from RIT with [<sup>177</sup>Lu]Lu-DOTA-panitumumab F(ab')<sub>2</sub>.<h4>Results</h4>Panitumumab F(ab')<sub>2</sub> were conjugated to DOTA and complexed to <sup>64</sup>Cu or <sup>177</sup>Lu in high radiochemical purity (95.6 ± 2.1% and 96.7 ± 3.5%, respectively) and exhibited high affinity EGFR binding (K<sub>d</sub> = 2.9 ± 0.7 × 10<sup>- 9</sup> mol/L). Biodistribution (BOD) studies at 6, 24 or 48 h post-injection (p.i.) of [<sup>64</sup>Cu]Cu-DOTA-panitumumab F(ab')<sub>2</sub> (5.5-14.0 MBq; 50 μg) or [<sup>177</sup>Lu]Lu-DOTA-panitumumab F(ab')<sub>2</sub> (6.5 MBq; 50 μg) in NRG mice with s.c. HNSCC patient-derived xenografts (PDX) overall showed no significant differences in tumour uptake but modest differences in normal organ uptake were noted at certain time points. Tumours were imaged by microPET/CT with [<sup>64</sup>Cu]Cu-DOTA-panitumumab F(ab')<sub>2</sub> or microSPECT/CT with [<sup>177</sup>Lu]Lu-DOTA-panitumumab F(ab')<sub>2</sub> but not with irrelevant [<sup>177</sup>Lu]Lu-DOTA-trastuzumab F(ab')<sub>2</sub>. Tumour uptake at 24 h p.i. of [<sup>64</sup>Cu]Cu-DOTA-panitumumab F(ab')<sub>2</sub> [14.9 ± 1.1% injected dose/gram (%ID/g) and [<sup>177</sup>Lu]Lu-DOTA-panitumumab F(ab')<sub>2</sub> (18.0 ± 0.4%ID/g) were significantly higher (P < 0.05) than [<sup>177</sup>Lu]Lu-DOTA-trastuzumab F(ab')<sub>2</sub> (2.6 ± 0.5%ID/g), demonstrating EGFR-mediated tumour uptake. There were no significant differences in the radiation equivalent doses in the tumour and most normal organs estimated for [<sup>177</sup>Lu]Lu-DOTA-panitumumab F(ab')<sub>2</sub> based on the BOD of [<sup>64</sup>Cu]Cu-DOTA-panitumumab F(ab')<sub>2</sub> compared to those estimated directly from the BOD of [<sup>177</sup>Lu]Lu-DOTA-panitumumab F(ab')<sub>2</sub> except for the liver and whole body which were modestly underestimated by [<sup>64</sup>Cu]Cu-DOTA-panitumumab F(ab')<sub>2</sub>. Region-of-interest (ROI) analysis of microPET/CT images provided dose estimates for the tumour and liver that were not significantly different for the two radioimmunoconjugates. Human doses from administration of [<sup>177</sup>Lu]Lu-DOTA-panitumumab F(ab')<sub>2</sub> predicted that a 2 cm diameter HNSCC tumour in a patient would receive 1.1-1.5 mSv/MBq and the whole body dose would be 0.15-0.22 mSv/MBq.<h4>Conclusion</h4>A PET theranostic strategy combining [<sup>64</sup>Cu]Cu-DOTA-panitumumab F(ab')<sub>2</sub> to image HNSCC tumours and predict the equivalent radiation doses in the tumour and normal organs from RIT with [<sup>177</sup>Lu]Lu-DOTA-panitumumab F(ab')<sub>2</sub> is feasible. RIT with [<sup>177</sup>Lu]Lu-DOTA-panitumumab F(ab')<sub>2</sub> may be a promising approach to treatment of HNSCC due to frequent overexpression of EGFR.
Project description:Gastrin-releasing peptide receptors (GRPRs) are overexpressed in prostate cancer and are suitable for targeted radionuclide therapy (TRT). We optimized the bombesin-derived GRPR-antagonist PEG2 -RM26 for labeling with 177 Lu and further determined the effect of treatment with 177 Lu-labeled peptide alone or in combination with the anti-HER2 antibody trastuzumab in a murine model. The PEG2 -RM26 analog was coupled to NOTA, NODAGA, DOTA and DOTAGA chelators. The peptide-chelator conjugates were labeled with 177 Lu and characterized in vitro and in vivo. A preclinical therapeutic study was performed in PC-3 xenografted mice. Mice were treated with intravenous injections (6 cycles) of (A) PBS, (B) DOTAGA-PEG2 -RM26, (C) 177 Lu-DOTAGA-PEG2 -RM26, (D) trastuzumab or (E) 177 Lu-DOTAGA-PEG2 -RM26 in combination with trastuzumab. 177 Lu-DOTAGA-PEG2 -RM26 demonstrated quantitative labeling yield at high molar activity (450 GBq/?mol), high in vivo stability (5 min pi >98% of radioligand remained when coinjected with phosphoramidon), high affinity to GRPR (KD = 0.4?±?0.2 nM), and favorable biodistribution (1 hr pi tumor uptake was higher than in healthy tissues, including the kidneys). Therapy with 177 Lu-DOTAGA-PEG2 -RM26 induced a significant inhibition of tumor growth. The median survival for control groups was significantly shorter than for treated groups (Group C 66 days, Group E 74 days). Trastuzumab together with radionuclide therapy significantly improved survival. No treatment-related toxicity was observed. In conclusion, based on in vitro and in vivo characterization of the four 177 Lu-labeled PEG2 -RM26 analogs, we concluded that 177 Lu-DOTAGA-PEG2 -RM26 was the most promising analog for TRT. Radiotherapy using 177 Lu-DOTAGA-PEG2 -RM26 effectively inhibited tumor growth in vivo in a murine prostate cancer model. Anti-HER2 therapy additionally improved survival.
Project description:<h4>Purpose</h4>It was previously demonstrated that radiation effects can enhance the therapy outcome of immune checkpoint inhibitors. In this study, a syngeneic breast tumor mouse model was used to investigate the effect of [<sup>177</sup>Lu]Lu-DOTA-folate as an immune stimulus to enhance anti-CTLA-4 immunotherapy.<h4>Methods</h4>In vitro and in vivo studies were performed to characterize NF9006 breast tumor cells with regard to folate receptor (FR) expression and the possibility of tumor targeting using [<sup>177</sup>Lu]Lu-DOTA-folate. A preclinical therapy study was performed over 70 days with NF9006 tumor-bearing mice that received vehicle only (group A); [<sup>177</sup>Lu]Lu-DOTA-folate (5 MBq; 3.5 Gy absorbed tumor dose; group B); anti-CTLA-4 antibody (3 × 200 μg; group C), or both agents (group D). The mice were monitored regarding tumor growth over time and signs indicating adverse events of the treatment.<h4>Results</h4>[<sup>177</sup>Lu]Lu-DOTA-folate bound specifically to NF9006 tumor cells and tissue in vitro and accumulated in NF9006 tumors in vivo. The treatment with [<sup>177</sup>Lu]Lu-DOTA-folate or an anti-CTLA-4 antibody had only a minor effect on NF9006 tumor growth and did not substantially increase the median survival time of mice (23 day and 19 days, respectively) as compared with untreated controls (12 days). [<sup>177</sup>Lu]Lu-DOTA-folate sensitized, however, the tumors to anti-CTLA-4 immunotherapy, which became obvious by reduced tumor growth and, hence, a significantly improved median survival time of mice (> 70 days). No obvious signs of adverse effects were observed in treated mice as compared with untreated controls.<h4>Conclusion</h4>Application of [<sup>177</sup>Lu]Lu-DOTA-folate had a positive effect on the therapy outcome of anti-CTLA-4 immunotherapy. The results of this study may open new perspectives for future clinical translation of folate radioconjugates.
Project description:<h4>Background</h4>In this work, a lutetium-177 (<sup>177</sup>Lu) production method based on the separation of nuclear isomers, <sup>177m</sup>Lu & <sup>177</sup>Lu, is reported. The <sup>177m</sup>Lu-<sup>177</sup>Lu separation is performed by combining the use of DOTA & DOTA-labelled peptide (DOTATATE) and liquid-liquid extraction.<h4>Methods</h4>The <sup>177m</sup>Lu cations were complexed with DOTA & DOTATATE and kept at 77?K for periods of time to allow <sup>177</sup>Lu production. The freed <sup>177</sup>Lu ions produced via internal conversion of <sup>177m</sup>Lu were then extracted in dihexyl ether using 0.01?M di-(2-ethylhexyl) phosphoric acid (DEHPA) at room temperature. The liquid-liquid extractions were performed periodically for a period up to 35?days.<h4>Results</h4>A maximum <sup>177</sup>Lu/<sup>177m</sup>Lu activity ratio of 3500?±?500 was achieved with [<sup>177m</sup>Lu]Lu-DOTA complex, in comparison to <sup>177</sup>Lu/<sup>177m</sup>Lu activity ratios of 1086?±?40 realized using [<sup>177m</sup>Lu]Lu-DOTATATE complex. The <sup>177</sup>Lu-<sup>177m</sup>Lu separation was found to be affected by the molar ratio of lutetium and DOTA. A <sup>177</sup>Lu/<sup>177m</sup>Lu activity ratio up to 3500?±?500 was achieved with excess DOTA in comparison to <sup>177</sup>Lu/<sup>177m</sup>Lu activity ratio 1500?±?600 obtained when lutetium and DOTA were present in molar ratio of 1:1. Further, the <sup>177</sup>Lu ion extraction efficiency, decreases from 95?±?4% to 58?±?2% in the presence of excess DOTA.<h4>Conclusion</h4>The reported method resulted in a <sup>177</sup>Lu/ <sup>177m</sup>Lu activity ratio up to 3500 after the separation. This ratio is close to the lower end of <sup>177</sup>Lu/<sup>177m</sup>Lu activity ratios, attained currently during the direct route <sup>177</sup>Lu production for clinical applications (i.e. 4000-10,000). This study forms the basis for further extending the liquid-liquid extraction based <sup>177m</sup>Lu-<sup>177</sup>Lu separation in order to lead to a commercial <sup>177m</sup>Lu/<sup>177</sup>Lu radionuclide generator.
Project description:A bifunctional derivative of the versatile acyclic chelator H4octapa, p-SCN-Bn-H4octapa, has been synthesized for the first time. The chelator was conjugated to the HER2/neu-targeting antibody trastuzumab and labeled in high radiochemical purity and specific activity with the radioisotopes (111)In and (177)Lu. The in vivo behavior of the resulting radioimmunoconjugates was investigated in mice bearing ovarian cancer xenografts and compared to analogous radioimmunoconjugates employing the ubiquitous chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). The H4octapa-trastuzumab conjugates displayed faster radiolabeling kinetics with more reproducible yields under milder conditions (15 min, RT, ~94-95%) than those based on DOTA-trastuzumab (60 min, 37 °C, ~50-88%). Further, antibody integrity was better preserved in the (111)In- and (177)Lu-octapa-trastuzumab constructs, with immunoreactive fractions of 0.99 for each compared to 0.93-0.95 for (111)In- and (177)Lu-DOTA-trastuzumab. These results translated to improved in vivo biodistribution profiles and SPECT imaging results for (111)In- and (177)Lu-octapa-trastuzumab compared to (111)In- and (177)Lu-DOTA-trastuzumab, with increased tumor uptake and higher tumor-to-tissue activity ratios.
Project description:In recent reports, we have shown that optimized pretargeted radioimmunotherapy (PRIT) based on molecularly engineered antibody conjugates and <sup>177</sup>Lu-DOTA chelate (DOTA-PRIT) can be used to cure mice bearing human solid tumor xenografts using antitumor antibodies to minimally internalizing membrane antigens, GPA33 (colon) and GD2 (neuroblastoma). However, many solid tumor membrane antigens are internalized after antibody binding and it is generally believed that internalizing tumor membrane antigens are not suitable targets for PRIT. In this study, we tested the hypothesis that DOTA-PRIT can be performed successfully to target HER2, an internalizing membrane antigen widely expressed in breast, ovarian, and gastroesophageal junction cancers. <b>Methods:</b> DOTA-PRIT was carried out in athymic nude mice bearing BT-474 xenografts, a HER2-expressing human breast cancer, using a three-step dosing regimen consisting of sequential intravenous administrations of: 1) a bispecific IgG-scFv (210 kD) format (BsAb) carrying the IgG sequence of the anti-HER2 antibody trastuzumab and the scFv "C825" with high-affinity, hapten-binding antibody for Bn-DOTA (metal) (BsAb: anti-HER2-C825), 2) a 500 kD dextran-based clearing agent, followed by 3) <sup>177</sup>Lu-DOTA-Bn. At the time of treatment, athymic nude mice bearing established subcutaneous BT-474 tumors (medium- and smaller-sized tumors with tumor volumes of 209 ± 101 mm<sup>3</sup> and ranging from palpable to 30 mm<sup>3</sup>, respectively), were studied along with controls. We studied single- and multi-dose regimens. For groups receiving fractionated treatment, we verified quantitative tumor targeting during each treatment cycle using non-invasive imaging with single-photon emission computed tomography/computed tomography (SPECT/CT). <b>Results:</b> We achieved high therapeutic indices (TI, the ratio of radiation-absorbed dose in tumor to radiation-absorbed dose to critical organs, such as bone marrow) for targeting in blood (TI = 28) and kidney (TI = 7), while delivering average radiation-absorbed doses of 39.9 cGy/MBq to tumor. Based on dosimetry estimates, we implemented a curative fractionated therapeutic regimen for medium-sized tumors that would deliver approximately 70 Gy to tumors, which required treatment with a total of 167 MBq <sup>177</sup>Lu-DOTA-Bn/mouse (estimated absorbed tumor dose: 66 Gy). This regimen was well tolerated and achieved 100% complete responses (CRs; defined herein as tumor volume equal to or smaller than 4.2 mm<sup>3</sup>), including 62.5% histologic cure (5/8) and 37.5% microscopic residual disease (3/8) at 85 days (d). Treatment controls showed tumor progression to 207 ± 201% of pre-treatment volume at 85 d and no CRs. Finally, we show that treatment with this curative <sup>177</sup>Lu regimen leads to a very low incidence of histopathologic abnormalities in critical organs such as bone marrow and kidney among survivors compared with non-treated controls. <b>Conclusion:</b> Contrary to popular belief, we demonstrate that DOTA-PRIT can be successfully adapted to an internalizing antigen-antibody system such as HER2, with sufficient TIs and absorbed tumor doses to achieve a high probability of cures of established human breast cancer xenografts while sparing critical organs of significant radiotoxicity.
Project description:Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin receptor (SSTR) analogs is a common approach in advanced neuroendocrine neoplasms. Recently, SSTR antagonists have shown promising results for imaging and therapy due to a higher number of binding sites than in commonly used agonists. We evaluated PRRT with SSTR agonist <sup>177</sup>Lu-DOTATOC and antagonist <sup>177</sup>Lu-DOTA-JR11 longitudinally in an orthotopic murine pancreatic neuroendocrine neoplasm model expressing human SSTR2. Morphologic and metabolic changes during treatment were assessed using multimodal imaging, including hybrid PET/MRI and SPECT/CT. <b>Methods:</b> In vitro radioligand binding and internalization assays and cell-cycle analysis were performed. SSTR2-transfected BON cells (BON-SSTR2) were used for in vivo experiments. Tumor-bearing mice received 2 intravenous injections of 100 μL of saline, 30 MBq of <sup>177</sup>Lu-DOTATOC, or 20 MBq of <sup>177</sup>Lu-DOTA-JR11 with an interval of 3 wk. Weekly T2-weighted MRI was performed for tumor monitoring. Viability of the tumor tissue was assessed by <sup>18</sup>F-FDG PET/MRI once after PRRT. Tumor and kidney uptake of the respective radiopharmaceuticals was measured 24 h after injection by SPECT/CT. <b>Results:</b> Compared with <sup>177</sup>Lu-DOTATOC, <sup>177</sup>Lu-DOTA-JR11 treatment resulted in an increased accumulation of cells in G2/M phase. Animals treated with the SSTR antagonist showed a significant reduction in tumor size (<i>P</i> < 0.001) and an increased median survival (207 d; interquartile range [IQR], 132-228) compared with <sup>177</sup>Lu-DOTATOC (126 d; IQR, 118-129). SPECT/CT revealed a 4-fold higher median tumor uptake for the antagonist and a 3-fold higher tumor-to-kidney ratio in the first treatment cycle. During the second therapy cycle, tumor uptake of <sup>177</sup>Lu-DOTATOC was significantly lower (<i>P</i> = 0.01) whereas <sup>177</sup>Lu-DOTA-JR11 uptake remained stable. Imaging of tumor morphology indicated comparatively larger necrotic fractions for <sup>177</sup>Lu-DOTA-JR11 despite further tumor growth. These results were confirmed by <sup>18</sup>F-FDG PET, revealing the least amount of viable tumor tissue in <sup>177</sup>Lu-DOTA-JR11-treated animals, at 6.2% (IQR, 2%-23%). <b>Conclusion:</b> <sup>177</sup>Lu-DOTA-JR11 showed a higher tumor-to-kidney ratio and a more pronounced cytotoxic effect than did <sup>177</sup>Lu-DOTATOC. Additionally, tumor uptake was more stable over the course of 2 treatment cycles.
Project description:Affibody-mediated PNA-based pretargeting is a promising approach to radionuclide therapy of HER2-expressing tumors. In this study, we test the hypothesis that shortening the PNA pretargeting probes would increase the tumor-to-kidney dose ratio. The primary probe Z<sub>HER2:342</sub>-SR-<i>HP15</i> and the complementary secondary probes <i>HP16</i>, <i>HP17</i>, and <i>HP18</i>, containing 9, 12, and 15 nucleobases, respectively, and carrying a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator were designed, synthesized, characterized in vitro, and labeled with <sup>177</sup>Lu. In vitro pretargeting was studied in HER2-expressing SKOV3 and BT474 cell lines. The biodistribution of these novel probes was evaluated in immunodeficient mice bearing SKOV3 xenografts and compared to the previously studied [<sup>177</sup>Lu]Lu-<i>HP2</i>. Characterization confirmed the formation of high-affinity duplexes between <i>HP15</i> and the secondary probes, with the affinity correlating with the length of the complementary PNA sequences. All the PNA-based probes were bound specifically to HER2-expressing cells in vitro. In vivo studies demonstrated HER2-specific uptake of all <sup>177</sup>Lu-labeled probes in xenografts in a pretargeting setting. The ratio of cumulated radioactivity in the tumor to the radioactivity in kidneys was dependent on the secondary probe's size and decreased with an increased number of nucleobases. The shortest PNA probe, [<sup>177</sup>Lu]Lu-<i>HP16</i>, showed the highest tumor-to-kidney ratio. [<sup>177</sup>Lu]Lu-<i>HP16</i> is the most promising secondary probe for affibody-mediated tumor pretargeting.
Project description:<h4>Purpose</h4>Paired imaging/therapy with radiolabeled somatostatin receptor (SSTR) antagonists is a novel approach in neuroendocrine tumors (NETs). The aim of this study was to compare tumor uptake of <sup>68</sup>Ga-DOTA-JR11 and <sup>177</sup>Lu-satoreotide tetraxetan (<sup>177</sup>Lu-DOTA-JR11) in patients with NETs.<h4>Methods</h4>As part of a prospective clinical trial, 20 patients with metastatic NETs underwent <sup>68</sup>Ga-DOTA-JR11 PET/CT and serial imaging with <sup>177</sup>Lu-satoreotide tetraxetan. PET/CT and SPECT/CT parameters for lesion uptake and absorbed dose of <sup>177</sup>Lu-satoreotide tetraxetan in lesions were compared using linear regression analysis and Pearson correlation.<h4>Results</h4>A total of 95 lesions were analyzed on <sup>68</sup>Ga-DOTA-JR11 PET/CT and <sup>177</sup>Lu-satoreotide tetraxetan SPECT/CT. SUVs and tumor-to-normal-tissue ratios on PET/CT and SPECT/CT were significantly correlated (p < 0.01), but the degree of correlation was modest with Pearson correlation coefficients ranging from 0.3 to 0.7. Variation in intrapatient lesional correlation was observed. Nevertheless, in all patients, the lesion SUVpeak uptake ratio for <sup>177</sup>Lu-satoreotide tetraxetan vs. <sup>68</sup>Ga-DOTA-JR11 was high; even in those with low uptake on <sup>68</sup>Ga-DOTA-JR11 PET/CT (SUVpeak ≤ 10), a ratio of 8.0 ± 5.2 was noted. Correlation of SUVpeak of <sup>68</sup>Ga-DOTA-JR11 with projected <sup>177</sup>Lu-satoreotide tetratexan-absorbed dose (n = 42) was modest (r = 0.5, p < 0.01), while excellent correlation of SUVpeak of <sup>177</sup>Lu-satoreotide tetraxetan with projected <sup>177</sup>Lu-satoreotide tetraxetan-absorbed dose was noted (r = 0.9, p < 0.0001).<h4>Conclusion</h4>Our study shows that <sup>68</sup>Ga-DOTA-JR11 PET can be used for patient selection and PRRT and that low tumor uptake on PET should not preclude patients from treatment with <sup>177</sup>Lu-satoreotide tetraxetan. The ability to use single time-point SPECT/CT for absorbed dose calculations could facilitate dosimetry regimens, save costs, and improve patient convenience.