Title of article :
177Lu-DOTA-HYNIC-Lys(Nal)-Urea-Glu: Biokinetics, Dosimetry, and Evaluation in Patients with Advanced Prostate Cancer
Author/Authors :
Santos-Cuevas, Clara Departamento de Materiales Radiactivos - Instituto Nacional de Investigaciones Nucleares (ININ) - Ocoyoacac - Estado de Mexico, Mexico , Ferro-Flores, Guillermina Departamento de Materiales Radiactivos - Instituto Nacional de Investigaciones Nucleares (ININ) - Ocoyoacac - Estado de Mexico, Mexico , Garcıa-Perez, Francisco O Departamento de Medicina Nuclear - Instituto Nacional de Cancerologıa - Ciudad de Mexico, Mexico , Jimenez-Mancilla, Nallely Instituto Nacional de Investigaciones Nucleares (ININ) - Ocoyoacac - Estado de Mexico, Mexico , Ramırez-Nava, Gerardo Departamento de Materiales Radiactivos - Instituto Nacional de Investigaciones Nucleares (ININ) - Ocoyoacac - Estado de Mexico, Mexico , Ocampo-Garcıa, Blanca Departamento de Materiales Radiactivos - Instituto Nacional de Investigaciones Nucleares (ININ) - Ocoyoacac - Estado de Mexico, Mexico , Luna-Gutierrez, Myrna Departamento de Materiales Radiactivos - Instituto Nacional de Investigaciones Nucleares (ININ) - Ocoyoacac - Estado de Mexico, Mexico , Azorın-Vega, Erika Departamento de Materiales Radiactivos - Instituto Nacional de Investigaciones Nucleares (ININ) - Ocoyoacac - Estado de Mexico, Mexico , Davanzo, Jenny Departamento de Medicina Nuclear - Instituto Nacional de Cancerologıa - Ciudad de Mexico, Mexico , Soldevilla-Gallardo, Irma Departamento de Medicina Nuclear - Instituto Nacional de Cancerologıa - Ciudad de Mexico, Mexico
Abstract :
SPECT/CT images in patients have demonstrated the ability of [99mTc]Tc-EDDA/HYNIC-Lys(Nal)-Urea-Glu ([99mTc]Tc-iPSMA)
to detect tumors and metastases of prostate cancer. Considering that theranostics combines the potential of therapeutic and
diagnostic radionuclides in the same molecular probe, the aim of this research was to estimate the biokinetics and dosimetry of
177Lu-DOTA-HYNIC-Lys(Nal)-Urea-Glu (177Lu-iPSMA) in healthy subjects and analyze the response in patients receiving 177LuiPSMA therapeutic doses. 177Lu-iPSMA was obtained from lyophilized formulations with radiochemical purities >98%. Wholebody images from ¡ve healthy subjects were acquired at 20 min, 6, 24, 48, and 120 h after 177Lu-iPSMA administration (185 MBq).
The image sequence was used to extrapolate the 177Lu-iPSMA time-activity curves of each organ to adjust the biokinetic model and
calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM
code to calculate internal radiation doses. Ten patients (median age: 68 y; range 58–86 y) received from 1 to 4 cycles of 177LuiPSMA (3.7 or 7.4 GBq) every 8–10 weeks. Response was evaluated using the 68Ga-PSMA-ligand-PET/CT or 99mTc-iPSMASPECT/CT diagnostic images and serum PSA levels before and after 177Lu-iPSMA treatment. The blood activity showed a half-life
value of 1.1 h for the fast component (T1/2α = ln2/0.614), 9.2 h for the ¡rst slow component (T1/2β = ln2/0.075), and 79.6 h for the
second slow component (T1/2c = ln2/0.008). The average absorbed doses were 0.23, 0.28, 0.88, and 1.17 Gy/GBq for the spleen,
liver, kidney, and salivary glands. A total of 18 cycles were performed in 10 patients. A PSA decrease and some reduction of the
radiotracer uptake (SUV) in tumor lesions occurred in 60% and 70% of the patients, respectively. 177Lu-iPSMA obtained from kit
formulations showed high tumor uptake with good response rates in patients. The results obtained in this study warrant further
clinical studies to establish the optimal number of treatment cycles and for evaluating the e«ect of this therapeutic agent on
survival of patients.
