Individualisation of radiation protection recommendations for patients treated with [177Lu]Lu-DOTA-TATE.

BACKGROUND: As for any other nuclear medicine treatment, patients treated with [177Lu]Lu-DOTA-TATE should be given some radiation protection recommendations after being discharged to limit the dose received by family members and public. The restriction periods will depend on the remaining activity at the time of discharge, the washout rate and patients' personal conditions. The activity in patients' whole-body follows a bi-exponential behaviour. At the time of discharge only the first part of the time-activity curve is known. However, the second phase of the bi-exponential curve should be known to individualize the time of restrictions. The main purpose of this prospective study was to establish a simple method for calculating the restriction periods based on measurements taken before discharge. METHODS: The whole-body time-activity curve was calculated for 20 patients from dose-rate measurements performed during the first week post-administration. An effective decay time [Formula: see text] was calculated from a mono-exponential fit performed with the 6 h and 24 h measurements and compared with the effective decay time [Formula: see text] obtained from the mono-exponential fit performed with the 24 h, 48 h and 168 h measurements. The differences between them were calculated and the 95th percentile of these differences was used as a correction factor for [Formula: see text]. A modified effective decay [Formula: see text] was obtained by adding the correction factor to [Formula: see text] and the restriction periods for each patient was calculated. The whole body activity washout between the first and the fourth treatment cycles of 16 patients was also compared. RESULTS: The comparison of the whole-body activity curves between the first and the fourth cycle of the treatment for 16 patients would indicate that the recommendations on radiation protection determined from the first cycle could reasonably be used for the remaining cycles in most patients. The values of [Formula: see text] and [Formula: see text] obtained for the 20 patients were significantly different. The 95th percentile of the differences between [Formula: see text] and [Formula: see text] was 46 h, which is thus the time to be added to [Formula: see text] so as to determine the restriction periods. CONCLUSIONS: The proposed method makes it possible to calculate the restriction periods for patients treated with [177Lu]Lu-DOTA-TATE before they leave the hospital in a conservative and individualized way.

Activity recovery for differently shaped objects in quantitative SPECT.

Objective.The aim was to theoretically and experimentally investigate recovery in SPECT images with objects of different shapes. Furthermore, the accuracy of volume estimation by thresholding was studied for those shapes.Approach.Nine spheres, nine oblate spheroids, and nine prolate spheroids phantom inserts were used, of which the six smaller spheres were part of the NEMA IEC body phantom and the rest of the inserts were 3D-printed. The inserts were filled with99mTc and177Lu. When filled with99mTc, SPECT images were acquired in a Siemens Symbia Intevo Bold gamma camera and when filled with177Lu in a General Electric NM/CT 870 DR gamma camera. The signal rate per activity (SRPA) was determined for all inserts and represented as a function of the volume-to-surface ratio and of the volume-equivalent radius using VOIs defined according to the sphere dimensions and VOIs defined using thresholding. Experimental values were compared with theoretical curves obtained analytically (spheres) or numerically (spheroids), starting from the convolution of a source distribution with a point-spread function. Validation of the activity estimation strategy was performed using four 3D-printed ellipsoids. Lastly, the threshold values necessary to determine the volume of each insert were obtained.Main results.Results showed that SRPA values for the oblate spheroids diverted from the other inserts, when SRPA were represented as a function of the volume-equivalent radius. However, SRPA values for all inserts followed a similar behaviour when represented as a function of the volume-to-surface ratio. Results for ellipsoids were in agreement with those results. For the three types of inserts the volume could be accurately estimated using a threshold method for volumes larger than 25 ml.Significance.Determination of SRPA independently of lesion or organ shape should decrease uncertainties in estimated activities and thereby, in the long term, be beneficial to patient care.

The role of BRAF V600E mutation in post-surgical 131I therapy in papillary thyroid carcinoma: a study based on SPECT-CT uptake analysis.

BACKGROUND: The BRAF V600E mutation (BRAF mut) in papillary thyroid cancer (PTC) has been associated with poor response to therapy with 131I in patients with metastases but the results in postsurgical treatment are controversial. Our main objective is to investigate the impact of the mutation on the biokinetics of the administered 131I therapy after surgery. METHODS: A prospective study was designed, from July 2015 to January 2018 which included patients with PTC receiving 131I therapy after surgical treatment. To study the biokinetics of the radioiodine in postoperative thyroid remnants, SPECT-CT images were acquired so as to obtain the following variables: percentage of remnant uptake at 2 and 7 days post-administration, effective half-life and time-integrated activity coefficient. All of them were compared depending on the mutational diagnosis and other clinical features and pathological variables. RESULTS: Sixty-one patients, and in total 103 thyroid remnants, were included. About 59% of patients were BRAF mutated. The mutation was associated with classic variant (88.5% vs. 11.5%; P=0.0001), desmoplastic reaction (85.7% vs. 14.3%; P=0.002), smaller tumor size (1.5 vs. 2.1 cm; P=0.024), nodal disease (3.3 vs. 1; P=0.001) and advanced stages (76.9% vs. 23%; P=0.014). The BRAFmut group had a lower percentage of 131I uptake at 2 days (0.17% vs. 0.47%; P=0.001) and at 7 days (0.02% vs. 0.1%; P=0.013); and a lower time-integrated activity coefficient (0.05h vs. 0.17 h; P=0.002). In univariate analysis, in addition to the mutation, the histological variant was significant but only for time-integrated activity coefficient (P=0.04). In multivariate analysis, only mutation determined the 2-day uptake (P<0.001) and the time-integrated activity coefficient (P<0.001). CONCLUSIONS: The BRAF V600E mutation is associated with lower 131I uptake in thyroid remnants. Furthermore, it is an independent factor that decreases the effect of post-surgical 131I therapy, and therefore, it could be used as a potential tool to optimize the treatment of PTC.

Microdosimetry-based determination of tumour control probability curves for treatments with 225Ac-PSMA of metastatic castration resistant prostate cancer.

We performed Monte Carlo simulations in order to determine, by means of microdosimetry calculations, tumour control probability (TCP) curves for treatments with 225Ac-PSMA of metastatic castration resistant prostate cancer (mCRPC). Realistic values of cell radiosensitivity, nucleus size and lesion size were used for calculations. As the cell radiosensitivity decreased, the nucleus size decreased and the lesion size increased, the absorbed dose to reach a given TCP increased. The widest variations occurred with regard to the cell radiosensitivity. For the Monte Carlo simulations, in order to address a non-uniform PSMA expression, different 225Ac-PSMA distributions were considered. The effect of these different PSMA distributions resulted in small variations in the TCP curves (maximum variation of 5%). Absorbed doses to reach a TCP of 0.9 for a uniform 225Ac-PSMA distribution, considering a relative biological effectiveness (RBE) of 5, ranged between 35.0 Gy and 116.5 Gy. The lesion absorbed doses per administered activity reported in a study on treatments with 225Ac-PSMA of mCRPC ranged between 1.3 Gy MBq-1 and 9.8 Gy MBq-1 for a RBE = 5. For a 70 kg-patient to whom 100 kBq kg-1 of 225Ac-PSMA are administered, the range of lesion absorbed doses would be between 9.1 Gy and 68.6 Gy. Thus, for a single cycle of 100 kBq kg-1, a number of lesions would not receive an absorbed dose high enough to reach a TCP of 0.9.

Mutación del gen BRAF V600E en el cáncer papilar de tiroides y su efecto en la terapia con yodo radiactivo (131I) posquirúrgica: ¿deberíamos modificar nuestra estrategia terapéutica? / BRAF V600E mutation in papillary thyroid cancer and its effect on postoperative radioiodine (131I) therapy: Should we modify our therapeutic strategy?

INTRODUCCIÓN: La mutación BRAF V600E en el cáncer papilar de tiroides (CPT) parece asociarse a una resistencia al 131I. Nuestro principal objetivo fue cuantificar la respuesta al 131I tras la cirugía tanto en pacientes que presentaban la mutación (BRAF+) como en los que no presentaban el gen mutado (BRAF-). MÉTODO: Estudio prospectivo de los CPT intervenidos y tratados con 131I desde septiembre de 2015 hasta enero de 2017. VARIABLES: edad, género, estadio tumoral, histológicas, tiroglobulina antes de 131I, a las 48h y a los 6 meses; dosis absorbida y % de actividad a los 2 y a los 7días y tiempo de eliminación. RESULTADOS: Cuarenta y un pacientes y 67 restos tiroideos. El 61% eran BRAF+. En los estadios III y IV, el 80% eran BRAF+. En el vaciamiento ganglionar terapéutico, el 100% eran BRAF+. El número de ganglios fue superior en BRAF+: 3,4 vs 1,2 (p = 0,01). La variante clásica fue predominante en BRAF+ (91,7% vs 8,3%; p = 0,03). El 85,7% vs 14,3% de los BRAF+ tuvieron reacción desmoplásica (p = 0,02). Los BRAF+ presentaban menor dosis absorbida respecto a la actividad administrada (5,4 vs 20Gy/MBq; p = 0,02); menor % de actividad respecto a la unidad de masa a los 2 (0,046 vs 0,103%/g; p = 0,02) y a los 7 días (0,006 vs 0,034%/g, p = 0,04). CONCLUSIONES: La mutación del gen BRAF V600E se relaciona con una mayor resistencia al tratamiento posquirúrgico con 131I desde el inicio de la enfermedad

INTRODUCTION: The BRAF V600E mutation in papillary thyroid cancer (PTC) has been associated with resistance to 131I. Our aim was to quantify the response to 131I after surgery in patients who had the mutation (BRAF+) and those who did not have the mutated gene (BRAF-). METHOD: A prospective cohort study was designed, from September 2015 to February 2016, which included patients with PTC receiving therapy after surgical treatment. Variables were described for age, gender, histology, tumor stage, thyroglobulin values before, 48 h after and 6months after 131I; absorbed dose and % activity on days 2 and 7 and elimination time. RESULTS: 41 patients giving in total 67 thyroid remnants were included. 61% were BRAF+. In stagesiii and IV, 80% were BRAF+. In lateral resection, 100% were BRAF+. The number of nodes was higher in BRAF+: 3.4 vs 1.2 (P = .01). The classic variant was predominant in BRAF+ (91.7% vs 8.3%, P = .03). 85.7% vs 14.3% of BRAF+ had desmoplastic reaction (P = .02). The BRAF+ had a lower absorbed dose than the administered activity (5.4Gy/MBq vs 20Gy/MBq, P = .02); lower% activity with respect to the unit of mass at 2 (0.046%/g vs 0.103%/g, P = .02) and at 7days (0.006%/gr vs 0.034%/gr, P = .04) CONCLUSIONS: The mutation of the BRAF V600E gene is related with greater resistance to postoperative treatment with 131I since the onset of the disease

BRAF V600E mutation in papillary thyroid cancer and its effect on postoperative radioiodine (131I) therapy: Should we modify our therapeutic strategy? / Mutación del gen BRAF V600E en el cáncer papilar de tiroides y su efecto en la terapia con yodo radiactivo (131I) posquirúrgica: ¿deberíamos modificar nuestra estrategia terapéutica?

INTRODUCTION: The BRAF V600E mutation in papillary thyroid cancer (PTC) has been associated with resistance to 131I. Our aim was to quantify the response to 131I after surgery in patients who had the mutation (BRAF+) and those who did not have the mutated gene (BRAF-). METHOD: A prospective cohort study was designed, from September 2015 to February 2016, which included patients with PTC receiving therapy after surgical treatment. Variables were described for age, gender, histology, tumor stage, thyroglobulin values before, 48h after and 6months after 131I; absorbed dose and % activity on days 2 and 7 and elimination time. RESULTS: 41 patients giving in total 67 thyroid remnants were included. 61% were BRAF+. In stagesiii and iv, 80% were BRAF+. In lateral resection, 100% were BRAF+. The number of nodes was higher in BRAF+: 3.4 vs 1.2 (P=.01). The classic variant was predominant in BRAF+ (91.7% vs 8.3%, P=.03). 85.7% vs 14.3% of BRAF+ had desmoplastic reaction (P=.02). The BRAF+ had a lower absorbed dose than the administered activity (5.4Gy/MBq vs 20Gy/MBq, P=.02); lower% activity with respect to the unit of mass at 2 (0.046%/g vs 0.103%/g, P=.02) and at 7days (0.006%/gr vs 0.034%/gr, P=.04) CONCLUSIONS: The mutation of the BRAF V600E gene is related with greater resistance to postoperative treatment with 131I since the onset of the disease.