Linfogammagrafía para la evaluación de trastornos del flujo linfático de las extremidades: informe de estándares de procedimientos técnicos de un panel de expertos de medicina nuclear italiano / Lymphoscintigraphy for the evaluation of limb lymphatic flow disorders: report of technical procedural standards from an Italian Nuclear Medicine expert panel

La linfogammagrafía representa el patrón para el diagnóstico del linfedema, pero una limitación importante es la falta de estandarización de los procedimientos. El objetivo de este panel de expertos italiano es proporcionar un estándar de procedimiento para la linfogammagrafía en la evaluación de los trastornos del sistema linfático. Se deben evitar los geles anestésicos tópicos que contengan lidocaína. Los pacientes deben retirar los apósitos compresivos. La actividad total recomendada para la administración de 99mTc-nanocoloides en adultos es de 74MBq, o 37MBq por miembro y por compartimento investigado, en alícuotas simples o múltiples. Se deben realizar 2-3 inyecciones subcutáneas (II-III+/-I espacio interdigital de cada mano/pie), evitando la inyección intravascular. El sistema linfático profundo de los miembros inferiores debe evaluarse en presencia de reflujo dérmico o estasis linfática (1-2 administraciones subfasciales en la región retromaleolar o plantar). Las imágenes planares deben ser tomadas desde el sitio de la inyección hasta el hígado, con adquisiciones estáticas de cuerpo entero o en serie de 20' y 90' después de la administración subcutánea. Se obtiene información adicional sobre las vías linfáticas después de un protocolo de ejercicio rápido y/o prolongado. Se recomienda SPECT/TC para estudiar los territorios torácicos, abdominales y pélvicos. Cuando sea necesario, el sistema linfático profundo de los miembros inferiores debe ser evaluado con adquisición estática a 90' después de la administración subfascial. El informe debe describir el procedimiento de administración e imágenes, el protocolo de ejercicio, el análisis cualitativo y semicuantitativo (tasa de lavado, índice de transporte) y las posibles fuentes de error. Dado el papel esencial que desempeña la linfogammagrafía en el tratamiento clínico del linfedema primario y secundario, se debe hacer un esfuerzo para la estandarización de esta técnica a fin de proporcionar a los médicos una metodología técnica homogénea y fiable

Lymphoscintigraphy represents the "gold standard" for diagnosis of lymphedema, but an important limitation is the lack of procedural standardization. The aim of this Italian expert panel was to provide a procedural standard for lymphoscintigraphy in the evaluation of lymphatic system disorders. Topic anaesthetic gels containing lidocaine should be avoided. Patients should remove compressive dressings. Total recommended activity for 99mTc-nanocolloid administration in adults is 74MBq, or 37MBq per limb and per investigated compartment, in single or multiple aliquots.2-3 subcutaneous injections should be performed (II-III+/-I interdigital space of each hand/foot), avoiding intravascular injection. Deep lymphatic system of lower limbs should be evaluated in presence of dermal back-flow or lymphatic stasis (1-2 subfascial administrations in retro-malleolar or plantar region). Planar images should be acquired from injection site to liver with whole-body or serial static acquisitions 20' and 90' after subcutaneous administration. Additional information on lymphatic pathways is obtained after a quick and/or prolonged exercise protocol. SPECT/CT is recommended to study the thoracic, abdominal and pelvic territories. When required, deep lymphatic system of lower limbs should be evaluated with static acquisition 90' after subfascial administration. The report should describe administration and imaging procedure, exercise protocol, qualitative and semi-quantitative analysis (wash-out rate, transport index), potential sources of error. Due to the essential role fulfilled by lymphoscintigraphy in clinical management of primary and secondary lymphedema, an effort for the standardization of this technique should be made to provide the clinicians with a homogeneous and reliable technical methodology

Lymphoscintigraphy for the evaluation of limb lymphatic flow disorders: Report of technical procedural standards from an Italian Nuclear Medicine expert panel. / Linfogammagrafía para la evaluación de trastornos del flujo linfático de las extremidades: informe de estándares de procedimientos técnicos de un panel de expertos de medicina nuclear italiano.

Lymphoscintigraphy represents the "gold standard" for diagnosis of lymphedema, but an important limitation is the lack of procedural standardization. The aim of this Italian expert panel was to provide a procedural standard for lymphoscintigraphy in the evaluation of lymphatic system disorders. Topic anaesthetic gels containing lidocaine should be avoided. Patients should remove compressive dressings. Total recommended activity for 99mTc-nanocolloid administration in adults is 74MBq, or 37MBq per limb and per investigated compartment, in single or multiple aliquots. 2-3 subcutaneous injections should be performed (II-III±I interdigital space of each hand/foot), avoiding intravascular injection. Deep lymphatic system of lower limbs should be evaluated in presence of dermal back-flow or lymphatic stasis (1-2 subfascial administrations in retro-malleolar or plantar region). Planar images should be acquired from injection site to liver with whole-body or serial static acquisitions 20' and 90' after subcutaneous administration. Additional information on lymphatic pathways is obtained after a quick and/or prolonged exercise protocol. SPECT/CT is recommended to study the thoracic, abdominal and pelvic territories. When required, deep lymphatic system of lower limbs should be evaluated with static acquisition 90' after subfascial administration. The report should describe administration and imaging procedure, exercise protocol, qualitative and semi-quantitative analysis (wash-out rate, transport index), potential sources of error. Due to the essential role fulfilled by lymphoscintigraphy in clinical management of primary and secondary lymphedema, an effort for the standardization of this technique should be made to provide the clinicians with a homogeneous and reliable technical methodology.

Dosimetry-Based Consideration on Remission and Relapse after Therapy with 223Ra-Dichloride in Castration-Resistant Prostate Cancer (CRPC) with Bone Metastases. A Case Report.

Here, we present the case of a 64-year-old male patient diagnosed with castration-resistant prostate cancer (CRPC) with bone metastasis, treated with abiraterone prednisone/prednisolone in combination with 223Ra-dichloride therapy, who had remission and a subsequent relapse of bone metastasis on repeated bone scans after therapy. We also discuss the possibility of continuing the 223Ra-dichloride therapy over the six planned administrations by administering other cycles at the same dose or at higher doses, if shown to be devoid of a significant increase in side effects, based on dosimetry considerations.

Gamma camera calibrations for the Italian multicentre study for lesion dosimetry in 223Ra therapy of bone metastases.

PURPOSE: The aim was to calibrate gamma cameras in the framework of the Italian multicentre study for lesion dosimetry in 223Ra therapy of bone metastases. Equipments of several manufacturers and different models were used. METHODS: Eleven gamma cameras (3/8- and 5/8-inch crystal) were used, acquiring planar static images with double-peak (82 and 154keV, 20% wide) and MEGP collimator. The sensitivity was measured in air, varying source-detector distance and source size. Transmission curves were measured, calculating the parameters used for attenuation/scatter correction with the pseudo-extrapolation number method, and assessing their variations with the source size. RESULTS: Values of the calibration factor (geometric mean of both detector sensitivities) ranged from 41.1 to 113.9cps/MBq. For the smallest source (diameter of 3.5cm), the calibration factor decrease ranged from -30% to -4%, highlighting the importance of partial volume effects according to the equipment involved. The sensitivity variation with the source-detector distance, with respect to the 15cm-value, reached 10% (in absolute value) in the range 5-30cm, but fixing the distance between the two heads, the calibration factor variation with the distance from the midline was within 3.6%. Appreciable variation of the transmission curves with the source size were observed, examining the results obtained with six gamma cameras. CONCLUSION: Assessments of sensitivity and transmission curve variations with source size should be regularly implemented in calibration procedures. The results of this study represent a useful compendium to check the obtained calibrations for dosimetric purposes.

A case report of image-based dosimetry of bone metastases with Alpharadin ((223)Ra-dichloride) therapy: inter-fraction variability of absorbed dose and follow-up.

A 70-year-old man affected by bone metastases from castration resistant prostate cancer underwent Alpharadin ((223)Ra-dichloride) therapy (6 administrations of 50 kBq per kg i.v., once every 4 weeks). The inter-fraction variability of the absorbed dose to lesions was evaluated for four injections. Dosimetric assessments were performed following the MIRD approach and a recently published methodology. The mean absorbed dose and standard deviation for 4 lesions [mean (σ %)] were: 434 mGy (15%) and 516 mGy (21%) for the right and left humeral head, 1205 mGy (14%) and 781 mGy (8%) for the right and left glenoid. The estimated total absorbed dose after the whole treatment, considering also the relative-biological effectiveness of alpha particles (RBE = 5), yielded a D RBE range of 13-36 Gy. A good correlation between (99m)Tc and (223)Ra uptake was obtained (R (2) = 0.7613). The tumour-non-tumour (TNT) ratio of 8 lesions (those above, plus 4 additional), monitored by six (99m)Tc-MDP bone scans over a period of about 10 months, evidenced a TNT reduction in two lesions (-42 and -48 %), but in most lesions the TNT remained fairly constant, evidencing that (223)Ra-dichloride therapy tends to prevent further progression of osseous disease, leading to chronicity of the metastatic status.

Dosimetry of bone metastases in targeted radionuclide therapy with alpha-emitting (223)Ra-dichloride.

PURPOSE: Ra-dichloride is an alpha-emitting radiopharmaceutical used in the treatment of bone metastases from castration-resistant prostate cancer. Image-based dosimetric studies remain challenging because the emitted photons are few. The aim of this study was to implement a methodology for in-vivo quantitative planar imaging, and to assess the absorbed dose to lesions using the MIRD approach. METHODS: The study included nine Caucasian patients with 24 lesions (6 humeral head lesions, 4 iliac wing lesions, 2 scapular lesions, 5 trochanter lesions, 3 vertebral lesions, 3 glenoid lesions, 1 coxofemoral lesion). The treatment consisted of six injections (one every 4 weeks) of 50 kBq per kg body weight. Gamma-camera calibrations for (223)Ra included measurements of sensitivity and transmission curves. Patients were statically imaged for 30 min, using an MEGP collimator, double-peak acquisition, and filtering to improve the image quality. Lesions were delineated on (99m)Tc-MDP whole-body images, and the ROIs superimposed on the (223)Ra images after image coregistration. The activity was quantified with background, attenuation, and scatter correction. Absorbed doses were assessed deriving the S values from the S factors for soft-tissue spheres of OLINDA/EXM, evaluating the lesion volumes by delineation on the CT images. RESULTS: In 12 lesions with a wash-in phase the biokinetics were assumed to be biexponential, and to be monoexponential in the remainder. The optimal timing for serial acquisitions was between 1 and 5 h, between 18 and 24 h, between 48 and 60 h, and between 7 and 15 days. The error in cumulated activity neglecting the wash-in phase was between 2 % and 12 %. The mean effective half-life (T 1/2eff) of (223)Ra was 8.2 days (range 5.5-11.4 days). The absorbed dose (D) after the first injection was 0.7 Gy (range 0.2-1.9 Gy. Considering the relative biological effectiveness (RBE) of alpha particles (RBE = 5), D RBE = 899 mGy/MBq (range 340-2,450 mGy/MBq). The percent uptake of (99m)Tc and (223)Ra (activity extrapolated to t = 0) were significantly correlated. CONCLUSION: The feasibility of in vivo quantitative imaging in (223)Ra therapy was confirmed. The lesion uptake of (223)Ra-dichloride was significantly correlated with that of (99m)Tc-MDP. The D RBE to lesions per unit administered activity was much higher than that of other bone-seeking radiopharmaceuticals, but considering a standard administration of 21 MBq (six injections of 50 kBq/kg to a 70-kg patient), the mean cumulative value of D RBE was about 19 Gy, and was therefore in the range of those of other radiopharmaceuticals. The macrodosimetry of bone metastases in treatments with (223)Ra-dichloride is feasible, but more work is needed to demonstrate its helpfulness in predicting clinical outcomes.

Improving the dose-myelotoxicity correlation in radiometabolic therapy of bone metastases with 153Sm-EDTMP.

PURPOSE: (153)Sm-ethylene diamine tetramethylene phosphonic acid ((153)Sm-EDTMP) is widely used to palliate pain from bone metastases, and is being studied for combination therapy beyond palliation. Conceptually, red marrow (RM) dosimetry allows myelotoxicity to be predicted, but the correlation is poor due to dosimetric uncertainty, individual sensitivity and biological effects from previous treatments. According to EANM guidelines, basic dosimetric procedures have been studied to improve the correlation between dosimetry and myelotoxicity in (153)Sm-EDTMP therapy. METHODS: RM dosimetry for 33 treatments of bone metastases from breast, prostate and lung tumours was performed prospectively (with (99m)Tc-MDP) and retrospectively, acquiring whole-body scans early and late after injection. The (153)Sm-EDTMP activity was calculated by prospective dosimetry based on measured skeletal uptake and full physical retention, with the RM absorbed dose not exceeding 3.8 Gy. Patient-specific RM mass was evaluated by scaling in terms of body weight (BW), lean body mass (LBM) and trabecular volume (TV) estimated from CT scans of the L2­L4 vertebrae. Correlations with toxicity were determined in a selected subgroup of 27 patients, in which a better correlation between dosimetry and myelotoxicity was expected. RESULTS: Skeletal uptakes of (99m)Tc and (153)Sm (Tc% and Sm%) were well correlated. The median Sm% was higher in prostate cancer (75.3 %) than in lung (60.5%, p = 0.005) or breast (60.8%, p = 0.008). PLT and WBC nadirs were not correlated with administered activity, but were weakly correlated with uncorrected RM absorbed doses, and the correlation improved after rescaling in terms of BW, LBM and TV. Most patients showed transient toxicity (grade 1­3), which completely and spontaneously recovered over a few days. Using TV, RM absorbed dose was in the range 2­5 Gy, with a median of 312 cGy for PLT in patients with toxicity and 247 cGy in those with no toxicity (p = 0.019), and 312 cGy for WBC in those with toxicity and 232 cGy in those with no toxicity (p = 0.019). ROC curves confirmed the correlations, yielding toxicity absorbed dose thresholds of 265 cGy for PLT and 232 cGy for WBC. CONCLUSION: The best predictor of myelotoxicity and blood cells nadir was obtained scaling the RM absorbed dose in terms of the estimated TV. It seems clear that the increase in skeletal uptake due to the presence of bone metastases and the assumption of full physical retention cause an overestimation of the RM absorbed dose. Nevertheless, an improvement of the dose­toxicity correlation is easily achievable by simple methods, also leading to possible improvement in multifactorial analyses of myelotoxicity.

Reduced value of thallium-201 single-photon emission computed tomography in the management of HIV-related focal brain lesions in the era of highly active antiretroviral therapy.

To evaluate the diagnostic value of thallium-201 single-photon emission computed tomography (201Tl SPECT) in the management of focal brain disorders in the era of highly active antiretroviral therapy (HAART), a validation study of diagnostic procedure was performed in a tertiary clinical care center in Italy. Thirty-eight consecutive HIV-infected patients with neurological impairment and focal brain lesions (FBL) were enrolled in a prospective evaluation and underwent diagnostic procedures according to a standardized protocol based on modified previously released guidelines. Six out of seven PCNSL presented high uptake at 201Tl SPECT [sensitivity 86% (95% CI 42-99); specificity 77% (95% CI 58-90); positive predictive value (PPV) 46% (95% CI 20-74); negative predictive value (NPV) 96% (95% CI 78-100)]. Among toxoplasmic encephalitis (TE) cases 14 showed no uptake and 5 showed an increased uptake [sensitivity 74% (95% CI 49-90); specificity 42% (95% CI 21-66); PPV 56% (95% CI 35-75); NPV 61% (95% CI 32-85)]. Patients taking HAART were more likely to display an increased uptake of 201Tl in the cerebral lesions than patients without HAART (OR 5.07; 95% CI 1.19-21.5). Considering only the patients with diagnosis of TE, 60% of patients who showed high radionuclide uptake were taking HAART, while 79% of patients without relevant uptake were not taking HAART. As a result of the impact of HAART, the diagnostic value of 201Tl SPECT in the management of HIV-associated FBL could be substantially reduced. This observation suggests that in HAART-treated patients, this diagnostic tool be used only when combined with other more specific diagnostic markers.