PSMA Radioligand Therapy in Prostate Cancer: Where Are We and Where Are We Heading?

ABSTRACT: Diagnosis and treatment of prostate cancer are complex and very challenging, being a major health care burden. The efficacy of radioligand therapy with prostate-specific membrane antigen agents has been proven beneficial in certain clinical indications. In this review, we describe management of prostate cancer patients according to current guidelines, especially focusing on the available clinical evidence for prostate-specific membrane antigen radioligand therapy.

Erratum: Single-center developing country analysis of radium-223 therapy in prostate cancer-preliminary results.

[This corrects the article on p. 352 in vol. 11, PMID: 34754606.].

Does TRODAT-1 SPECT Uptake Correlate with Cerebrospinal Fluid α-Synuclein Levels in Mid-Stage Parkinson's Disease?

BACKGROUND: Parkinson's disease (PD) is characterized by a progressive loss of nigrostriatal dopaminergic neurons with impaired motor and non-motor symptoms. It has been suggested that motor asymmetry could be caused due to an imbalance in dopamine levels, as visualized by dopamine transporter single emission computed tomography test (DAT-SPECT), which might be related to indirect measures of neurodegeneration, evaluated by the Montreal Cognitive Assessment (MOCA) and α-synuclein levels in the cerebrospinal fluid (CSF). Therefore, this study aimed to understand the correlation between disease laterality, DAT-SPECT, cognition, and α-synuclein levels in PD. METHODS: A total of 28 patients in the moderate-advanced stage of PD were subjected to neurological evaluation, TRODAT-1-SPECT/CT imaging, MOCA, and quantification of the levels of α-synuclein. RESULTS: We found that α-synuclein in the CSF was correlated with global cognition (positive correlation, r2 = 0.3, p = 0.05) and DAT-SPECT concentration in the putamen (positive correlation, r2 = 0.4, p = 0.005), and striatum (positive correlation, r2 = 0.2, p = 0.03), thus working as a neurodegenerative biomarker. No other correlations were found between DAT-SPECT, CSF α-synuclein, and cognition, thus suggesting that they may be lost with disease progression. CONCLUSIONS: Our data highlight the importance of understanding the dysfunction of the dopaminergic system in the basal ganglia and its complex interactions in modulating cognition.

Interictal and postictal 18F-FDG PET/CT in epileptogenic zone localization.

Objective: To evaluate the performance of 18F-fluorodeoxyglucose positron-emission tomography/computed tomography ( 18F-FDG PET/CT) in localizing epileptogenic zones, comparing 18F-FDG injection performed in the traditional interictal period with that performed near the time of a seizure. Materials and Methods: We evaluated patients with refractory epilepsy who underwent 18F-FDG PET/CT. The reference standards for localization of the epileptogenic zone were histopathology and follow-up examinations (in patients who underwent surgery) or serial electroencephalography (EEG) recordings, long-term video EEG, and magnetic resonance imaging (in patients who did not). The 18F-FDG injection was performed whether the patient had an epileptic seizure during the EEG monitoring period or not. The 18F-FDG PET/CT results were categorized as concordant or discordant with the reference standards. Results: Of the 110 patients evaluated, 10 were in a postictal group (FDG injection after a seizure) and 100 were in the interictal group. The 18F-FDG PET/CT was concordant with the reference standards in nine (90%) of the postictal group patients and in 60 (60%) of the interictal group patients. Among the nine postictal group patients in whom the results were concordant, the 18F-FDG PET/CT showed hypermetabolism and hypometabolism in the epileptogenic zone in four (44.4%) and five (55.6%), respectively. Conclusion: Our data indicate that 18F-FDG PET/CT is a helpful tool for localization of the epileptogenic zone and that EEG monitoring is an important means of correlating the findings. In addition, postictal 18F-FDG PET/CT is able to identify the epileptogenic zone by showing either hypometabolism or hypermetabolism.

Objetivo: Avaliar a capacidade da PET/CT FDG detectar a zona epileptogênica, com injeção da FDG realizada tanto no período interictal como perto de uma crise epiléptica. Materiais e Métodos: Foram avaliados pacientes com epilepsia de difícil controle que realizaram PET/CT FDG. A zona epileptogênica foi definida pelo follow up/anatomopatológico ou eletroencefalogramas (EEGs) seriados, telemetria e ressonância magnética. PET/CT FDG foi realizada independentemente se o paciente tinha crise epiléptica durante a monitoração com EEG ou no período interictal. Os resultados foram definidos como concordantes ou discordantes, comparando com a zona epileptogênica. Resultados: Foram incluídos no estudo 110 pacientes: 10 no grupo pós-ictal (injeção de FDG depois da crise) e 100 no grupo interictal. A PET/CT FDG foi concordante com a zona epileptogênica em nove pacientes do grupo pós-ictal (90%) e 60 pacientes do grupo interictal (60%). Entre os nove pacientes concordantes do grupo pós-ictal, quatro mostraram hipermetabolismo (44,4%) e cinco mostraram hipometabolismo na zona epileptogênica (55,6%). Conclusão: Nossos resultados confirmaram que a PET/CT FDG é uma ferramenta útil na localização da zona epileptogênica e a monitoração com EEG é muito importante para correlacionar os achados. Além disso, PET/CT FDG realizada no período pós-ictal é capaz de identificar a zona epileptogênica, mostrando tanto hipometabolismo como hipermetabolismo.

Interictal and postictal 18F-FDG PET/CT in epileptogenic zone localization / PET/CT FDG- 18F interictal e pós-ictal na localização da zona epileptogênica

Abstract Objective: To evaluate the performance of 18F-fluorodeoxyglucose positron-emission tomography/computed tomography ( 18F-FDG PET/CT) in localizing epileptogenic zones, comparing 18F-FDG injection performed in the traditional interictal period with that performed near the time of a seizure. Materials and Methods: We evaluated patients with refractory epilepsy who underwent 18F-FDG PET/CT. The reference standards for localization of the epileptogenic zone were histopathology and follow-up examinations (in patients who underwent surgery) or serial electroencephalography (EEG) recordings, long-term video EEG, and magnetic resonance imaging (in patients who did not). The 18F-FDG injection was performed whether the patient had an epileptic seizure during the EEG monitoring period or not. The 18F-FDG PET/CT results were categorized as concordant or discordant with the reference standards. Results: Of the 110 patients evaluated, 10 were in a postictal group (FDG injection after a seizure) and 100 were in the interictal group. The 18F-FDG PET/CT was concordant with the reference standards in nine (90%) of the postictal group patients and in 60 (60%) of the interictal group patients. Among the nine postictal group patients in whom the results were concordant, the 18F-FDG PET/CT showed hypermetabolism and hypometabolism in the epileptogenic zone in four (44.4%) and five (55.6%), respectively. Conclusion: Our data indicate that 18F-FDG PET/CT is a helpful tool for localization of the epileptogenic zone and that EEG monitoring is an important means of correlating the findings. In addition, postictal 18F-FDG PET/CT is able to identify the epileptogenic zone by showing either hypometabolism or hypermetabolism.

Resumo Objetivo: Avaliar a capacidade da PET/CT FDG detectar a zona epileptogênica, com injeção da FDG realizada tanto no período interictal como perto de uma crise epiléptica. Materiais e Métodos: Foram avaliados pacientes com epilepsia de difícil controle que realizaram PET/CT FDG. A zona epileptogênica foi definida pelo follow up/anatomopatológico ou eletroencefalogramas (EEGs) seriados, telemetria e ressonância magnética. PET/CT FDG foi realizada independentemente se o paciente tinha crise epiléptica durante a monitoração com EEG ou no período interictal. Os resultados foram definidos como concordantes ou discordantes, comparando com a zona epileptogênica. Resultados: Foram incluídos no estudo 110 pacientes: 10 no grupo pós-ictal (injeção de FDG depois da crise) e 100 no grupo interictal. A PET/CT FDG foi concordante com a zona epileptogênica em nove pacientes do grupo pós-ictal (90%) e 60 pacientes do grupo interictal (60%). Entre os nove pacientes concordantes do grupo pós-ictal, quatro mostraram hipermetabolismo (44,4%) e cinco mostraram hipometabolismo na zona epileptogênica (55,6%). Conclusão: Nossos resultados confirmaram que a PET/CT FDG é uma ferramenta útil na localização da zona epileptogênica e a monitoração com EEG é muito importante para correlacionar os achados. Além disso, PET/CT FDG realizada no período pós-ictal é capaz de identificar a zona epileptogênica, mostrando tanto hipometabolismo como hipermetabolismo.

Validation of Convolutional Neural Networks for Fast Determination of Whole-Body Metabolic Tumor Burden in Pediatric Lymphoma.

18F-FDG PET/CT quantification of whole-body tumor burden in lymphoma is not routinely performed because of the lack of fast methods. Although the semiautomatic method is fast, it is not fast enough to quantify tumor burden in daily clinical practice. Our purpose was to evaluate the performance of convolutional neural network (CNN) software in localizing neoplastic lesions in whole-body 18F-FDG PET/CT images of pediatric lymphoma patients. Methods: The retrospective image dataset, derived from the data pool of the International Atomic Energy Agency (coordinated research project E12017), included 102 baseline staging 18F-FDG PET/CT studies of pediatric lymphoma patients (mean age, 11 y). The images were quantified to determine the whole-body tumor burden (whole-body metabolic tumor volume [wbMTV] and whole-body total lesion glycolysis [wbTLG]) using semiautomatic software and CNN-based software. Both were displayed as semiautomatic wbMTV and wbTLG and as CNN wbMTV and wbTLG. The intraclass correlation coefficient (ICC) was applied to evaluate concordance between the CNN-based software and the semiautomatic software. Results: Twenty-six patients were excluded from the analysis because the software was unable to perform calculations for them. In the remaining 76 patients, CNN and semiautomatic wbMTV tumor burden metrics correlated strongly (ICC, 0.993; 95% CI, 0.989 - 0.996; P < 0.0001), as did CNN and semiautomatic wbTLG (ICC, 0.999; 95% CI, 0.998-0.999; P < 0.0001). However, the time spent calculating these metrics was significantly (<0.0001) less by CNN (mean, 19 s; range, 11-50 s) than by the semiautomatic method (mean, 21.6 min; range, 3.2-62.1 min), especially in patients with advanced disease. Conclusion: Determining whole-body tumor burden in pediatric lymphoma patients using CNN is fast and feasible in clinical practice.

Single-center developing country analysis of radium-223 therapy in prostate cancer-preliminary results.

We reviewed the records of mCRPC patients treated with off-label use of Ra-223. Ra-223 efficiency in this non-study population was correlated to outcome measures overall survival (OS), progression-free survival (PFS), bone event-free survival, bone marrow failure (BMF), and disease-related biomarkers. There were no limits regarding the number of prior hormonal agents or chemotherapy received before or during Ra-223. Exclusion criteria consisted of baseline platelet counts below 50,000/mm3 and/or absolute neutrophil counts below 1,500/mm3. Twenty-eight patients received 130 cycles of Ra-223 between 2017 and 2018. The overall median OS was 15.6 months. However, in patients submitted to 4 or fewer cycles, the median OS was 9.1 months; in contrast, the median OS was 18.5 months in patients submitted to 5 or 6 cycles. There was a significant inverse correlation between the number of cycles and the occurrence of bone events (76.2% of the patients that completed 6 cycles did not present bone events, while 71.4% of the patients that had skeletal-related events were submitted to less than 6 cycles). 82.1% of the patients were submitted to concomitant therapies with no significant side effects. There was also a decrease in ALP and LDH levels throughout treatment. Radium-223 increased OS and decreased bone events, especially when patients were able to complete 5-6 cycles. The proper selection of patients is crucial to improve outcomes.

The ratio between the whole-body and primary tumor burden, measured on 18F-FDG PET/CT studies, as a prognostic indicator in advanced non-small cell lung cancer.

OBJECTIVE: To determine whether the whole-body tumor burden, as quantified by 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT), is a prognostic indicator in advanced (stage III or IV) non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: This was a prospective study in which we evaluated 18F-FDG PET/CT staging parameters to quantify tumor burdens in patients with stage III or IV NSCLC. The following parameters were evaluated for the whole body (including the primary tumor) and for the primary tumor alone, respectively: maximum standardized uptake volume (wbSUVmax and tuSUVmax); metabolic tumor volume (wbMTV and tuMTV); and total lesion glycolysis (wbTLG and tuTLG). To determine whether the 18F-FDG PET/CT parameters were associated with overall survival (OS) and progression-free survival (PFS), we evaluated the wbSUVmax/tuSUVmax, wbMTV/tuMTV, and wbTLG/tuTLG ratios. RESULTS: 18F-FDG PET/CT was performed for staging in 52 patients who were followed for a median of 11.0 months (mean, 11.7 months). The estimated median PFS and OS were 9.6 months and 11.6 months, respectively. In the univariate analysis, OS was found to correlate significantly with wbTLG (hazard ratio [HR] = 1.001; 95% confidence interval [95 CI]: 1.000-1.001; p = 0.0361) and with the wbTLG/tuTLG ratio (HR = 1.705; 95% CI: 1.232-2.362; p = 0.0013). In the multivariate analysis, only the wbTLG/tuTLG ratio was independently associated with OS (HR = 1.660; 95% CI: 1.193-2.310; p = 0.0027). CONCLUSION: The wbTLG/tuTLG ratio is an independent prognostic indicator of OS in advanced-stage NSCLC.

OBJETIVO: Avaliar se a carga metabólica tumoral do corpo inteiro medida na tomografia por emissão de pósitrons/tomografia computadorizada com 18F-fluordesoxiglicose (18F-FDG PET/CT) é um indicador prognóstico em pacientes com câncer de pulmão de células não pequenas (CPCNP) em estágio avançado (estágio III ou IV). MATERIAIS E MÉTODOS: Avaliamos, prospectivamente, a carga tumoral na 18F-FDG-PET/CT de estadiamento em pacientes com CPCNP avançado. Os parâmetros avaliados do tumor primário (tu) e do corpo inteiro (wb) (incluindo o primário) foram: SUV máximo (wbSUVmax e tuSUVmax), volume metabólico tumoral (wbMTV e tuMTV), glicólise total da(s) lesão(ões) (wbTLG e tuTLG), além das seguintes razões: wbSUVmax/tuSUVmax, wbMTV/tuMTV e wbTLG/tuTLG. Os parâmetros medidos na 18F-FDG-PET/CT, variáveis clínicas e patológicas foram correlacionados com a sobrevida global (SG) e a sobrevida livre de progressão (SLP). RESULTADOS: 18F-FDG-PET/CT foi realizada em 52 pacientes (tempos mediano/médio de sobrevida = 11,0/11,7 meses). A SLP mediana foi de 9,6 meses e a SG foi de 11,6 meses. Houve correlação significativa da wbTLG (hazard ratio [HR] = 1,001; intervalo de confiança de 95% [IC 95%]: 1,000-1,001; p = 0,0361) e wbTLG/tuTLG (HR = 1,705; IC 95%: 1,232-2.362; p = 0,0013) com a SG. Na análise multivariada, a razão wbTLG/tuTLG associou-se independentemente com a SG (HR = 1,660; IC 95%: 1,193-2,310; p = 0,0027). CONCLUSÃO: A razão wbTLG/tuTLG é um indicador prognóstico independente de SG em CPCNP avançado.

The ratio between the whole-body and primary tumor burden, measured on 18F-FDG PET/CT studies, as a prognostic indicator in advanced non-small cell lung cancer / A relação entre a carga de doença de corpo inteiro e lesão primária medida em estudos de 18F-FDG PET/CT como um indicador prognóstico em câncer de pulmão não pequenas células avançado

Abstract Objective: To determine whether the whole-body tumor burden, as quantified by 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT), is a prognostic indicator in advanced (stage III or IV) non-small cell lung cancer (NSCLC). Materials and Methods: This was a prospective study in which we evaluated 18F-FDG PET/CT staging parameters to quantify tumor burdens in patients with stage III or IV NSCLC. The following parameters were evaluated for the whole body (including the primary tumor) and for the primary tumor alone, respectively: maximum standardized uptake volume (wbSUVmax and tuSUVmax); metabolic tumor volume (wbMTV and tuMTV); and total lesion glycolysis (wbTLG and tuTLG). To determine whether the 18F-FDG PET/CT parameters were associated with overall survival (OS) and progression-free survival (PFS), we evaluated the wbSUVmax/tuSUVmax, wbMTV/tuMTV, and wbTLG/tuTLG ratios. Results: 18F-FDG PET/CT was performed for staging in 52 patients who were followed for a median of 11.0 months (mean, 11.7 months). The estimated median PFS and OS were 9.6 months and 11.6 months, respectively. In the univariate analysis, OS was found to correlate significantly with wbTLG (hazard ratio [HR] = 1.001; 95% confidence interval [95 CI]: 1.000-1.001; p = 0.0361) and with the wbTLG/tuTLG ratio (HR = 1.705; 95% CI: 1.232-2.362; p = 0.0013). In the multivariate analysis, only the wbTLG/tuTLG ratio was independently associated with OS (HR = 1.660; 95% CI: 1.193-2.310; p = 0.0027). Conclusion: The wbTLG/tuTLG ratio is an independent prognostic indicator of OS in advanced-stage NSCLC.

Resumo Objetivo: Avaliar se a carga metabólica tumoral do corpo inteiro medida na tomografia por emissão de pósitrons/tomografia computadorizada com 18F-fluordesoxiglicose (18F-FDG PET/CT) é um indicador prognóstico em pacientes com câncer de pulmão de células não pequenas (CPCNP) em estágio avançado (estágio III ou IV). Materiais e Métodos: Avaliamos, prospectivamente, a carga tumoral na 18F-FDG-PET/CT de estadiamento em pacientes com CPCNP avançado. Os parâmetros avaliados do tumor primário (tu) e do corpo inteiro (wb) (incluindo o primário) foram: SUV máximo (wbSUVmax e tuSUVmax), volume metabólico tumoral (wbMTV e tuMTV), glicólise total da(s) lesão(ões) (wbTLG e tuTLG), além das seguintes razões: wbSUVmax/tuSUVmax, wbMTV/tuMTV e wbTLG/tuTLG. Os parâmetros medidos na 18F-FDG-PET/CT, variáveis clínicas e patológicas foram correlacionados com a sobrevida global (SG) e a sobrevida livre de progressão (SLP). Resultados: 18F-FDG-PET/CT foi realizada em 52 pacientes (tempos mediano/médio de sobrevida = 11,0/11,7 meses). A SLP mediana foi de 9,6 meses e a SG foi de 11,6 meses. Houve correlação significativa da wbTLG (hazard ratio [HR] = 1,001; intervalo de confiança de 95% [IC 95%]: 1,000-1,001; p = 0,0361) e wbTLG/tuTLG (HR = 1,705; IC 95%: 1,232-2.362; p = 0,0013) com a SG. Na análise multivariada, a razão wbTLG/tuTLG associou-se independentemente com a SG (HR = 1,660; IC 95%: 1,193-2,310; p = 0,0027). Conclusão: A razão wbTLG/tuTLG é um indicador prognóstico independente de SG em CPCNP avançado.

Knee radiosynovectomy with 153Sm-hydroxyapatite compared to 90Y-hydroxyapatite: initial results of a prospective trial.

INTRODUCTION: Radiosynovectomy (RS) with 90Y-hydroxyapatite (90Y-HyA) aims to control knee hemarthrosis in hemophiliac patients to prevent secondary arthropathy. However, knee RS using 153Sm-hydroxyapatite (153Sm-HyA) is considered less suitable due to the lower average soft tissue range and energy of 153Sm for large joints, such as the knees. PURPOSE: The objective of this investigation was to assess the efficacy and safety of knee RS with 153Sm-HyA, compared to 90Y-HyA. METHODS: Forty patients were prospectively assigned to undergo knee RS with 153Sm-HyA (n = 19) or with 90Y-HyA (n = 21). The frequency of hemarthrosis episodes before and after treatment were compared. RESULTS: After six months of knee RS, 153Sm-HyA and 90Y-HyA promoted a similar reduction of hemarthrosis episodes (50% and 66.7%, respectively). However, after 12 months of knee RS, the reduction of hemarthrosis episodes was significantly (p = 0.037) higher using 153Sm-HyA (87.5%) compared to 90Y-HyA (50.0%). This discrepancy was more pronounced (p = 0.002) for 153Sm-HyA compared to 90Y-HyA in adults/adolescents. CONCLUSION: Knee radiosynovectomy with 153Sm-HyA is safe, reduces hemarthrosis episodes after 12 months of treatments, especially in adults/adolescents and even with grades III/IV arthropathy, similar to 90Y-HyA. 90Y-HyA seems to promote better hemarthrosis control in small children.

PSMA whole-body tumor burden in primary staging and biochemical recurrence of prostate cancer.

PURPOSE: The objective of this study was to evaluate whether 68Ga-PSMA PET/CT whole-body tumor burden (PSMAwbtb) is associated with clinical parameters and laboratory parameters in prostate cancer patients. METHODS: We retrospectively evaluated prostate cancer patients submitted to PSMA PET/CT for primary staging purposes or due to biochemical recurrence (BR). PSMAwbtb metrics (total volume of PSMA-avid tumor (PSMA-TV)) and total uptake of PSMA-avid lesions (PSMA-TL) were calculated semi-automatically. Spearman's rank correlations between PSMAwbtb metrics and clinical, laboratory parameters (age, time-to-BR, years of diagnosis of prostate cancer, free and total serum PSA levels, and the Gleason score) and with the highest SUVmax of a lesion (hSUVmax) were analyzed. RESULTS: Among the 257 PSMA PET/CT studies, there were 46 scans (17.9%) performed for primary staging and 211 (82.1%) for BR. PSMA-TV and PSMA-TL were calculated for the 157 positive scans (58.8%), which were 43 patients (93.5%) in the primary staging group and 114 patients (54.0%) in the BR group. In the primary staging group, we observed a significant correlation between PSMA-TL and hSUVmax (p = 0.0021). In the BR group, there was a significant direct correlation between PSMA-TL and the variables age (p = 0.0031), total serum PSA values (p = < 0.0001), free serum PSA values (p = < 0.0001), and the hSUVmax (p = < 0.0001). Similar results were obtained for PSMA-TV. CONCLUSION: PSMAwbtb has a direct and positive correlation with serum PSA values and age in prostate cancer patients with BR.

99mTc-sestamibi SPECT/CT and 18F-FDG-PET/CT have similar performance but different imaging patterns in newly diagnosed multiple myeloma.

PURPOSE: F-fluorodeoxiglucose (F-FDG)-PET/CT has been widely used to evaluate multiple myeloma. Tc-sestamibi (MIBI) scintigraphy has also been proposed for assessing multiple myeloma, but its use with state-of-the-art single-photon emission computed tomography/computed tomography (SPECT/CT) technology has not been fully evaluated.This study aimed to compare these two imaging modalities in multiple myeloma staging. MATERIALS AND METHODS: Sixty-two patients with recently diagnosed multiple myeloma were submitted to whole-body F-FDG-PET/CT and whole-body MIBI scans plus SPECT/CT of the chest and abdomen/pelvis. Number of focal lesions, contiguous soft tissue involvement (CSTI), extramedullary lesions (EMLs) and diffuse bone marrow (BM) involvement were recorded. RESULTS: PET/CT was positive in 59 patients (95%) and MIBI SPECT/CT in 58 (93%) (P = 0.69). MIBI detected more diffuse bone marrow involvement than PET/CT (respectively 78 vs. 58% of the patients), while PET/CT demonstrated more focal lesions than MIBI SPECT/CT (81 vs. 54% of the patients) (P = 0.002). PET/CT detected EMLs in four subjects and MIBI in one subject. CSTI was found in 28 (45%) and 23 (37%) patients on PET/CT and MIBI images, respectively (P = 0.36). Three patients with lytic lesions and no FDG uptake were MIBI positive, and two subjects with lytic lesions without MIBI uptake were FDG positive. CONCLUSION: MIBI SPECT/CT performs similarly to F-FDG-PET/CT in identifying sites of active disease in multiple myeloma staging. MIBI is more efficient than FDG for detecting the diffuse involvement of bone marrow but less efficient for detecting focal lesions. Some patients presented a 'mismatch' pattern of FDG/MIBI uptake.

Typical Acute Traumatic Fracture Healing in an 83-Year-Old Man Undergoing 223Ra Treatment for Prostatic Cancer Bone Metastases.

We report the case of a fracture healing after Ra in an 83-year-old wheelchair-bound man with prostate castration-resistant adenocarcinoma treated due to uncontrollable pain from widespread bone metastases. The patient fractured both right tibia and fibula 15 days prior to the first Ra cycle. After the first cycle, there was complete remission of his metastatic bone pain; after the second cycle, he began walking with support, which helped improve fracture healing; and after the third cycle, he presented complete mobility. Posttreatment images showed consolidated fractures. By improving metastatic bone pain with Ra, consolidation of the insufficiency fracture was possible.

Radium-223 as an Approved Modality for Treatment of Bone Metastases.

Radium-223 dichloride (223Ra) is an α-emitter radionuclide approved for treatment of osteoblastic metastases in castrate-resistant prostate cancer (mCRPC) patients. 223Ra increases overall survival, improves bone pain, increases the median time to the first skeletal-related event, reduces the use of external beam radiation therapy for bone pain palliation, reduces the rates of spinal cord compression, and hospitalization. 223Ra therapy has minimal side effects; the most common hematological side effects are anemia, thrombocytopenia and neutropenia while the nonhematological side effects that may occur are bone pain flare, nausea, fatigue, and diarrhea. Alongside 223Ra therapy there are currently a variety of first-line therapeutic options available to treat mCRPC patients and much debate regarding the appropriate treatment algorithm for these patients and the possible combination of therapies among the ones available. In this article, we review the rationale behind 223Ra therapy as well as 223Ra mechanisms of action, biodistribution and dosimetry, optimal timing possibilities to initiate 223Ra in contrast to other treatments available, the association of 223Ra with other therapies and the means of evaluating patients in order to properly deliver to 223Ra therapy. Furthermore, we will discuss 223Ra dose administration possibilities, patient and dose preparation and the challenges of treatment response evaluation during and after 223Ra.

Head-to-head comparison of F-18 FDG PET/CT in radioidine refractory thyroid cancer patients with elevated versus suppressed TSH levels a pilot study.

INTRODUCTION: To perform a head-to-head comparison of the uptake pattern of F-18 fluorodeoxyglucose in positron emission computed tomography (FDG PET/CT) in radioiodine refractory thyroid carcinomas (RAIR) in the same patient under elevated TSH levels (eTSH) and suppressed TSH levels (sTSH). METHODS: FDG PET/CT studies were performed under two conditions: levothyroxine intake (sTSH) and 30 days after hormonal withdrawal (eTSH). SUVmax values and the number of lesions detected (local recurrence and metastases in cervical and distant lymph nodes, lungs and bone) where blindly evaluated. Blood serum TSH and Tg levels were obtained prior to both studies. FDG PET/CT imaging, neck ultrasound, biopsy and follow-up were considered the reference standard. RESULTS: Fifteen patients performed both eTSH and sTSH FDG PET/CT studies. Both were positive for metastases in 80% of the patients. eTSH FDG PET/CT studies did not reveal increased uptake (p = 0.0640) and did not demonstrate a higher number of lesions (p = 0.320) when compared to sTSH FDG PET/CT studies. There was no change in the clinical management of these patients. CONCLUSIONS: eTSH FDG PET/CT in patients with RAIR did not show more metastases in comparison to sTSH FDG PET/CT and there was no impact in clinical management of patients. Elevating TSH levels (whether by hormonal withdrawal or recombinant TSH) in patients being submitted to FDG PET/CT may not be necessary.

Validation of a Multifocal Segmentation Method for Measuring Metabolic Tumor Volume in Hodgkin Lymphoma.

Quantification of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) can be time-consuming. We evaluated the performance of an automatic multifocal segmentation (MFS) method of quantification in patients with different stages of Hodgkin lymphoma, using the multiple VOI (MV) method as reference. Methods: This prospective bicentric study included 50 patients with Hodgkin lymphoma who underwent staging 18F-FGD PET/CT. The examinations were centrally reviewed and processed with commercial MFS software to obtain MTV and TLG using 2 fixed relative thresholds (40% and 20% of SUVmax) for each lesion. All PET/CT scans were processed using the MV and MFS methods. Interclass correlation coefficients and Bland-Altman plots were used for statistical analysis. Repeated calculations of MTV and TLG values by 2 observers with different degrees of PET/CT imaging experience were used to ascertain interobserver agreement on the MFS method. Results: The means and SDs obtained for the MTV with MV and MFS were, respectively, 736 ± 856 mL and 660 ± 699 mL for the 20% threshold and 313 ± 359 mL and 372 ± 434 mL for the 40% threshold. The time spent calculating the MTV was much shorter with the MFS method than with the MV method (median time, 11.6 min [range, 1-30 min] and 64.4 min [range, 1-240 min], respectively), especially in patients with advanced disease. Time spent was similar in patients with localized disease. There were no statistical differences between the MFS values obtained by the 2 different observers. Conclusion: MTV and TLG calculations using MFS are reproducible, generate similar results to those obtained with MV, and are much less timing-consuming. Main differences between the 2 methods were related to difficulties in avoiding overlay of VOIs in the MV technique. MV and MFS perform equally well in patients with a small number of lesions.

Proposal for a Quantitative 18F-FDG PET/CT Metabolic Parameter to Assess the Intensity of Bone Involvement in Multiple Myeloma.

Many efforts have been made to standardize the interpretation of 18F-FDG PET/CT in multiple myeloma (MM) with qualitative visual analysis or with quantitative metabolic parameters using various methods for lesion segmentation of PET images. The aim of this study was to propose a quantitative method for bone and bone marrow evaluation of 18F-FDG PET/CT considering the extent and intensity of bone 18F-FDG uptake: Intensity of Bone Involvement (IBI). Whole body 18F-FDG PET/CT of 59 consecutive MM patients were evaluated. Compact bone tissue was segmented in PET images using a global threshold for HU of the registered CT image. A whole skeleton mask was created and the percentage of its volume with 18F-FDG uptake above hepatic uptake was calculated (Percentage of Bone Involvement - PBI). IBI was defined by multiplying PBI by mean SUV above hepatic uptake. IBI was compared with visual analysis performed by two experienced nuclear medicine physicians. IBI calculation was feasible in all images (range:0.00-1.35). Visual analysis categorized PET exams into three groups (negative/mild, moderate and marked bone involvement), that had different ranges of IBI (multi comparison analysis, p < 0.0001). There was an inverse correlation between the patients' hemoglobin values and IBI (r = -0.248;p = 0.02). IBI score is an objective measure of bone and bone marrow involvement in MM, allowing the categorization of patients in different degrees of aggressiveness of the bone disease. The next step is to validate IBI in a larger group of patients, before and after treatment and in a multicentre setting.

SPECT/CT with 99mTc-sestamibi for the evaluation of skeletal muscle perfusion after electrical muscle stimulation in athletes.

OBJECTIVE: The purpose of this study was to evaluate the effects of electrical muscle stimulation (EMS) on muscles, using 99mTc-sestamibi SPECT/CT. MATERIALS AND METHODS: We prospectively enrolled 20 consecutive male professional water polo players. The mean age was 25 years (range, 18-36 years). All athletes underwent 99mTc-sestamibi SPECT/CT of the thigh (rectus femoris and vastus medialis muscle groups) before and after EMS. Images were quantified to identify increases in perfusion after EMS. RESULTS: Before EMS, there were no significant differences between the right and left thigh (rectus femoris and vastus medialis muscles) in terms of perfusion (p = 0.4). However, the comparison between the pre- and post-EMS analyses of the same muscle groups showed significant differences in radiotracer uptake (p < 0.001), with a mean increase in perfusion of 128% for the rectus femoris muscle group (95% CI: 0.86-1.61) and 118% for the vastus medialis muscle group (95% CI: 0.96-1.79). CONCLUSION: 99mTc-sestamibi SPECT/CT is an objective means of evaluating blood flow in muscles submitted to EMS, which appears to promote significant increases in such blood flow.

OBJETIVO: O objetivo deste estudo foi avaliar o efeito da estimulação elétrica transcutânea na musculatura esquelética utilizando-se SPECT/CT com 99mTc- sestamibi. MATERIAIS E MÉTODOS: Foram prospectivamente avaliados 20 atletas masculinos de polo aquático (18-36 anos de idade; média de 25 anos). Todos os atletas foram submetidos a SPECT/CT com 99mTc- sestamibi das coxas antes e após estimulação elétrica transcutânea dos grupos musculares reto femoral e vasto medial. As imagens foram quantificadas para identificar aumento da perfusão. RESULTADOS: A comparação da perfusão dos grupos musculares (reto femoral e vasto medial) direito versus esquerdo durante o repouso não demonstrou diferença significativa (p = 0,4). Entretanto, quando comparados esses mesmos grupos musculares antes e após a estimulação elétrica, observou-se diferença significativa na captação do traçador (p < 0,001), com aumento perfusional médio de 128% do grupo reto femoral (IC 95%: 0,86-1,61) e 118% do grupo vasto medial (IC 95%: 0,96-1,79) no grupo estimulado. CONCLUSÃO: A SPECT/CT com 99mTc- sestamibi é capaz de demonstrar de forma objetiva que a estimulação elétrica transcutânea aumenta significativamente o fluxo sanguíneo muscular.

SPECT/CT with 99mTc-sestamibi for the evaluation of skeletal muscle perfusion after electrical muscle stimulation in athletes / SPECT/CT com sestamibi-99mTc para avaliação da perfusão após estímulo elétrico da musculatura esquelética em atletas

Abstract Objective: The purpose of this study was to evaluate the effects of electrical muscle stimulation (EMS) on muscles, using 99mTc-sestamibi SPECT/CT. Materials and Methods: We prospectively enrolled 20 consecutive male professional water polo players. The mean age was 25 years (range, 18-36 years). All athletes underwent 99mTc-sestamibi SPECT/CT of the thigh (rectus femoris and vastus medialis muscle groups) before and after EMS. Images were quantified to identify increases in perfusion after EMS. Results: Before EMS, there were no significant differences between the right and left thigh (rectus femoris and vastus medialis muscles) in terms of perfusion (p = 0.4). However, the comparison between the pre- and post-EMS analyses of the same muscle groups showed significant differences in radiotracer uptake (p < 0.001), with a mean increase in perfusion of 128% for the rectus femoris muscle group (95% CI: 0.86-1.61) and 118% for the vastus medialis muscle group (95% CI: 0.96-1.79). Conclusion: 99mTc-sestamibi SPECT/CT is an objective means of evaluating blood flow in muscles submitted to EMS, which appears to promote significant increases in such blood flow.

Resumo Objetivo: O objetivo deste estudo foi avaliar o efeito da estimulação elétrica transcutânea na musculatura esquelética utilizando-se SPECT/CT com 99mTc- sestamibi. Materiais e Métodos: Foram prospectivamente avaliados 20 atletas masculinos de polo aquático (18-36 anos de idade; média de 25 anos). Todos os atletas foram submetidos a SPECT/CT com 99mTc- sestamibi das coxas antes e após estimulação elétrica transcutânea dos grupos musculares reto femoral e vasto medial. As imagens foram quantificadas para identificar aumento da perfusão. Resultados: A comparação da perfusão dos grupos musculares (reto femoral e vasto medial) direito versus esquerdo durante o repouso não demonstrou diferença significativa (p = 0,4). Entretanto, quando comparados esses mesmos grupos musculares antes e após a estimulação elétrica, observou-se diferença significativa na captação do traçador (p < 0,001), com aumento perfusional médio de 128% do grupo reto femoral (IC 95%: 0,86-1,61) e 118% do grupo vasto medial (IC 95%: 0,96-1,79) no grupo estimulado. Conclusão: A SPECT/CT com 99mTc- sestamibi é capaz de demonstrar de forma objetiva que a estimulação elétrica transcutânea aumenta significativamente o fluxo sanguíneo muscular.

18F-FDG PET/CT performed immediately after percutaneous ablation to evaluate outcomes of the procedure: preliminary results.

OBJECTIVE: To determine whether 18F-fluorodeoxyglucose positron emission tomography/computed tomography performed immediately after percutaneous ablation (iPA 18F-FDG PET/CT) is useful in evaluating the outcomes of the procedure. MATERIALS AND METHODS: This was a retrospective study of 20 patients (13 males, 7 females; mean age, 65.8 ± 12.1 years) submitted to percutaneous ablation of metastases. All of the lesions treated had shown focal uptake on a 18F-FDG PET/CT scan obtained at baseline. The primary tumors were mainly colorectal cancer (in 45%) or lung cancer (in 40%). iPA 18F-FDG PET/CT was performed to identify any residual viable tumor cells. The treatment was considered a success (no viable tumor cells present) if no uptake of 18F-FDG was noted on the iPA 18F-FDG PET/CT scan. RESULTS: Twenty-six lesions were submitted to percutaneous ablation with either cryoablation (n = 7) or radiofrequency ablation (n = 19). The mean lesion diameter was 2.52 ± 1.49 cm. For the detection of viable tumor cells, iPA 18F-FDG PET/CT had a sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 66.7%, 95%, 88.5%, 80%, and 90.5%, respectively. There was a significant correlation between the iPA 18F-FDG PET/CT findings and the results of the follow-up studies (kappa = 0.66; p < 0.01). CONCLUSION: iPA 18F-FDG PET/CT studies appear to constitute a useful means of evaluating the outcomes of percutaneous ablation. By detecting residual viable tumor cells, this strategy might allow early re-intervention, thus reducing morbidity. Studies involving larger numbers of patients are needed in order to confirm our findings.

OBJETIVO: Demonstrar se a tomografia por emissão de pósitrons acoplada a tomografia computadorizada usando-se fluorodesoxiglicose marcada com flúor-18 realizada imediatamente após ablação percutânea (iAP 18F-FDG PET/CT) pode ser útil na avaliação do resultado desse tratamento. MATERIAIS E MÉTODOS: Foram avaliados, retrospectivamente, 20 pacientes (13 homens e 7 mulheres; média de idade: 65,8 ± 12,1 anos) submetidos a ablação percutânea de metástases apresentando captação de 18F-FDG no exame de PET/CT. Os tumores primários foram, principalmente, câncer colorretal (45%) ou câncer de pulmão (40%). A iAP 18F-FDG PET/CT foi realizada para avaliar tumor residual viável. O tratamento foi considerado sucesso (sem lesão viável) se nenhuma captação de 18F-FDG fosse observada na iAP 18F-FDG PET/CT. RESULTADOS: Vinte e seis lesões foram submetidas a ablação percutânea por meio de crioablação (n = 7) ou radiofrequência (n = 19). O tamanho médio das lesões era de 2,52 ± 1,49 cm. A iAP 18F-FDG PET/CT detectou tumor viável com sensibilidade, especificidade, acurácia, valor preditivo positivo e valor preditivo negativo de 66,7%, 95%, 88,5%, 80% e 90,5%, respectivamente. Houve correlação significativa entre os achados da iAP 18F-FDG PET/CT e os resultados do seguimento clínico dos pacientes (kappa = 0,66; p < 0,01). CONCLUSÃO: A iAP 18F-FDG PET/CT é capaz de avaliar o resultado da ablação percutânea e poderá permitir reintervenção precoce de lesões residuais viáveis, reduzindo a morbidade. Um número maior de pacientes é necessário para confirmar esses achados.