Efficacy and Safety of 225 Ac-DOTATATE in the Treatment of Neuroendocrine Neoplasms With High SSTR Expression.

PURPOSE: We aimed to evaluate the efficacy and safety of 225 Ac-DOTATATE targeted α therapy (TAT) in various neuroendocrine neoplasms (NENs) with high somatostatin receptor (SSTR) expression. PATIENTS AND METHODS: This single-center prospective study included 10 patients with histologically diagnosed NENs that exhibited increased SSTR expression on 68 Ga-DOTATATE PET/CT imaging. All patients received 225 Ac-DOTATATE TAT. The primary end points were molecular imaging-based response and disease control rate (DCR), measured using the slightly modified Positron Emission Tomography Response Criteria in Solid Tumors 1.0. The secondary end points were adverse event profiles and clinical responses. The adverse event profile was determined according to the Common Terminology Criteria for Adverse Events version 5.0. Clinical response was assessed using the EORTC QLQ-C30 v3.0 (European Organization for Research and Treatment of Cancer Core Quality of Life questionnaire version 3.0). RESULTS: A molecular imaging-based partial response was observed in 40% of all patients, SD in 40%, PD in 20%, and DCR in 80%. The DCR was 83.3% (5/6) in patients who were previously treated with 177 Lu-DOTATATE. According to the EORTC QLQ-C30 v3.0 score, most symptoms improved after 225 Ac-DOTATATE treatment, with only diarrhea showing no improvement. Grade III/IV hematological, kidney, and liver toxicities were not observed. The median follow-up time was 14 months (7-22 months), and no deaths were reported. CONCLUSIONS: This initial study suggests that 225 Ac-DOTATATE is a potentially promising option for treating NENs with elevated SSTR expression, with an acceptable toxicity profile and well-tolerated adverse effects.

Biodistribution and dosimetry of 177Lu-DOTA-IBA for therapy of bone metastases.

BACKGROUND: We designed and synthesized a novel bisphosphonate radiopharmaceutical (68 Ga- or 177Lu-labeled DOTA-ibandronate [68 Ga/177Lu-DOTA-IBA]) for the targeted diagnosis and treatment of bone metastases. The biodistribution and internal dosimetry of a single therapeutic dose of 177Lu-DOTA-IBA were evaluated using a series of single-photon emission computerized tomography (SPECT) images and blood samples. Five patients with multiple bone metastases were included in this prospective study. After receiving 1110 MBq 177Lu-DOTA-IBA, patients underwent whole-body planar, SPECT/CT imaging and venous blood sampling over 7 days. Dosimetric evaluation was performed for the main organs and tumor lesions. Safety was assessed using blood biomarkers. RESULTS: 177Lu-DOTA-IBA showed fast uptake, high retention in bone lesions, and rapid clearance from the bloodstream in all patients. In this cohort, the average absorbed doses (ADs) in the bone tumor lesions, kidneys, liver, spleen, red marrow, bladder-wall, and osteogenic cells were 5.740, 0.114, 0.095, 0.121, 0.095, and 0.333 Gy/GBq, respectively. Although no patient reached the predetermined dose thresholds, the red marrow will be the dose-limiting organ. There were no adverse reactions recorded after the administration of 1110 MBq 177Lu-DOTA-IBA. CONCLUSION: Dosimetric results show that the ADs for critical organs and total body are within the safety limit and with high bone retention. It is a promising radiopharmaceutical alternative for the targeted treatment of bone metastases, controlling its progression, and improving the survival and quality of life of patients with advanced bone metastasis.

Evaluation of 188Re-DTPA-deoxyglucose as a potential cancer radiopharmaceutical.

OBJECTIVE: We aimed to synthesize diethylenetriamine pentaacetic acid-deoxyglucose (DTPA-DG) radiolabeled with (188)Re and to evaluate its biologic characteristics using mammary tumor-bearing mice. MATERIALS AND METHODS: The biodistribution of the radiolabeled compound was determined by tissue counting at 3, 12, and 24 hours after injection in experimental animals. Scintigraphic examinations of nude mice bearing breast cancer (MCF-7 cells) were performed after (188)Re-DTPA-DG (18.5 MBq) was injected in the tail vein. For the tumor inhibitory portion of this work, tumor volumes were measured and recorded every 3 days until the 21st day after injection. RESULTS: The radiochemical purity of (188)Re-DTPA-DG was 95.0%. Based on biodistribution measurements, (188)Re-DTPA-DG was taken up at high levels by the tumor. The mean tumoral percent injected dosages per gram (% ID/g) were 1.98 +/- 0.29 (SD), 2.89 +/- 0.43, and 0.42 +/- 0.06 % ID/g at 3, 12, and 24 hours, respectively, after injection. In the (188)Re-DTPA-DG scintigraphic examinations, the tumors were clearly delineated on the images recorded 2, 4, 8, 12, and 24 hours after injection. In the tumor inhibitory evaluations, the tumor volume of the (188)Re-DTPA-DG-treated group increased more slowly than that of the control groups, which were treated with (188)Re-perrhenate or saline (p < 0.01). Rhenium-188-DTPA-DG showed excellent tumor targeting and tumor growth suppression properties on MCF-7 tumor cells. CONCLUSION: Rhenium-188-DTPA-DG may be a potential agent for the diagnosis and radiotherapy of tumors.

Preparation and imaging research on 188Re-DTPA-deoxyglucose in MCF-7 tumor-bearing mice.

OBJECTIVE: To investigate the preparation of (188)Re-diethylenetriaminepentaacetic acid-2-deoxyglucose ((188)Re-DTPA-DG) and its imaging quality and therapeutic effect. METHODS: Labeling of DTPA-DG with (188)Re was performed in the presence of stannous ion and sodium D-gluconate at a pH of 5.5 with 3 hours of incubation at 37 degrees C. The radiolabeling yields of (188)Re-DTPA-DG were determined by paper chromatography with a solution of acetone and saline (0.9% NaCl) as a developing agent. The imaging quality of (188)Re-DTPA-DG was determined by injecting 0.1 mL of a preparation having a radioactivity of 92.5GBq/L into the tail vein of nude mice bearing MCF-7 mammary tumors and imaging the tumors at 2, 4, 8, 12, and 24 hours after injection of the radiolabeled agent. Tumor volume was recorded every 2 or 3 days for 21 days. RESULTS: The radiochemical purity of the (188)Re-DTPA-DG complex was 95.0%. In the imaging study, the tumor-to-nontumor-tissue ratios (T/NT) of radioactivity at 12 and 24 hours after intravenous injection of the radiolabeled agent were 5.9 and 7.8, respectively. The tumor volume in the (188)Re-DTPA-DG-treated group of mice increased more slowly than that in the control group, and the two groups differed greatly in this measure at 21 days, with tumor volumes of 823.6 +/- 50.58 mm(3) and 1162.7 +/- 73.08 mm(3) in the (188)Re-DTPA-DG treated and control groups, respectively (p < 0.01). CONCLUSIONS: (188)Re-DTPA-DG showed excellent tumor targeting and tumor-growth-suppressing effects, and holds promise as an internal agent for tumor radiotherapy.

Noninvasive scintigraphic detection of tumor with 99mTc-DTPA-deoxyglucose: an experimental study.

OBJECTIVES: Glucosamine is a highly attractive scaffold for a glucosyl ligand, and shows activity with glucose transporters and hexokinase. In the study reported here, diethylenetriamine-pentaacetic acid-D-glucosamine (DTPA-DG) was synthesized by conjugating D-glucosamine to DTPA, and was labeled with technetium-99m ((99m)Tc). We investigated (99m)Tc-DTPA-DG for tumor detection. METHODS: The biodistribution and imaging of (99m)Tc-DTPA-DG in mammary tumor-bearing mice were compared to those in a control group of mice with oleum terebinthinae (turpentine oil)-induced inflammation. Both groups of mice were given an intravenous injection of 3.7 MBq/0.1 mL of (99m)Tc-DTPA-DG through the tail vein. RESULTS: (99m)Tc-DTPA-DG accumulated in the tumor tissue to a percentage of 2.10 +/- 0.02% of the injected dose per gram of tissue (%ID/g) at 2 hours after injection, versus an accumulation of 0.81 +/- 0.03%ID/g in the inflamed tissue. The tumor-to-contralateral muscle tissue ratio of (99m)Tc-DTPA-DG was 5.01 +/- 1.02, while the inflamed tissue-to-contralateral muscle tissue ratio was 1.2 +/- 0.08. Gamma-camera imaging revealed the tumor tissue at 2 hours after injection of (99m)Tc-DTPA-DG. The tumor-to-background ratio of (99m)Tc-DTPA-DG (3.8 +/- 0.95) at 2 hours was significantly (p < 0.05) higher in mammary tumor-bearing mice than was the inflamed tissue-to-background ratio (1.2 +/- 0.62) in the mice with inflammation. CONCLUSIONS: (99m)Tc-DTPA-DG showed excellent tumor targeting and has promise as an imaging agent for clinical tumor targeting.