18f-Fluorodeoxyglucose Positron Emission Tomography Versus Bone Marrow Biopsy for the Evaluation of Bone Marrow Infiltration in Newly Diagnosed Lymphoma Patients

ABSTRACT Background: Bone marrow evaluation (BME) is crucial for establishing an accurate staging and prognosis in lymphoma patients. Objective: The objective of the study was to study the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) against bone marrow biopsy (BMB) for BME. Methods: Five hundred patient files of newly diagnosed lymphoma patients treated at an academic medical center were reviewed for BME at diagnosis by BMB and FDG PET-CT. Diagnostic performance of FDG PET-CT for detecting bone marrow infiltration (BMI) was assessed, as well as clinical predictors for positive BMB and positive FDG PET-CT. Results: BMB was positive in 16.3% of all patients, and 28.7% had a positive FDG PET-CT for BMI. Overall, the sensitivity of FDG PET-CT was 74.1% and specificity 80.1%. As for predictors for BMB and FDG PET-CT positivity, B symptoms and thrombocytopenia were independent factors for BMI. Seventy-four patients had discordant results between BMB and FDG PET-CT, non-Hodgkin lymphoma (NHL) having the most significant discordance. This discrepancy did not affect treatment. Conclusions: FDG PET-CT shows excellent performance for the detection of BMI in Hodgkin lymphoma. For diffuse large B-cell lymphoma, we recommend performing BMB and FDG PET-CT as complementary tests. In all other NHL, a unilateral BMB is mandatory at diagnosis.

18f-Fluorodeoxyglucose Positron Emission Tomography Versus Bone Marrow Biopsy for the Evaluation of Bone Marrow Infiltration in Newly Diagnosed Lymphoma Patients.

BACKGROUND: Bone marrow evaluation (BME) is crucial for establishing an accurate staging and prognosis in lymphoma patients. OBJECTIVE: The objective of the study was to study the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) against bone marrow biopsy (BMB) for BME. METHODS: Five hundred patient files of newly diagnosed lymphoma patients treated at an academic medical center were reviewed for BME at diagnosis by BMB and FDG PET-CT. Diagnostic performance of FDG PET-CT for detecting bone marrow infiltration (BMI)was assessed, as well as clinical predictors for positive BMB and positive FDG PET-CT. RESULTS: BMB was positive in 16.3% of all patients, and 28.7% had a positive FDG PET-CT for BMI. Overall, the sensitivity of FDG PET-CT was 74.1% and specificity 80.1%. As for predictors for BMB and FDG PET-CT positivity, B symptoms and thrombocytopenia were independent factors for BMI. Seventy-four patients had discordant results between BMB and FDG PET-CT, non-Hodgkin lymphoma (NHL) having the most significant discordance. This discrepancy did not affect treatment. CONCLUSIONS: FDG PET-CT shows excellent performance for the detection of BMI in Hodgkin lymphoma. For diffuse large B-cell lymphoma, we recommend performing BMB and FDG PET-CT as complementary tests. In all other NHL, a unilateral BMB is mandatory at diagnosis.

Hybrid (2D/3D) Dosimetry of Radiolabeled Gold Nanoparticles for Sentinel Lymph Node Detection in Patients with Breast Cancer.

Previously, we reported the preparation and preclinical studies of 99mTc-labeled gold nanoparticles-mannose (99mTc-AuNP-mannose) with potential for sentinel lymph node (SLN) detection by using nuclear medicine procedures. This study aimed to evaluate the biokinetics and hybrid (2D/3D) dosimetry of 99mTc-AuNP-mannose in five patients with breast cancer under a sentinel lymph node detection protocol. Anterior and posterior whole-body planar images (2D, at 0.5, 2, 6, and 24 h) and single-photon emission computed tomography (3D at 6.5 h)/computed tomography (SPECT/CT) images were acquired after 99mTc-AuNP-mannose administration (37 MBq). Through a hybrid quantification method, activity in tissues of interest at the different acquisition times was determined and integrated over time to obtain the total nuclear transformations (N), as well as the mean residence time, in each tissue. N values and the OLINDA code were used for estimating the internal radiation absorbed doses. Results demonstrated that 99mTc-AuNP-mannose successfully accumulates and remains up to 24 h in the sentinel lymph node without detectable migration to other lymph nodes and no side effects on patients. Negligible absorption of the radiolabeled nanoparticles into the circulatory system was observed, from which the radio-nanosystem is rapidly eliminated by kidneys. Hybrid (2D/3D) dosimetry evaluations showed equivalent doses to SLN, breast, and kidneys of 172.34, 5.32, and 0.08 mSv/37 MBq, respectively, with an effective dose of 2.05E - 03 mSv/MBq. The mean effective residence time in SLN was 0.92 h. This preliminary study indicates that the use of 99mTc-AuNP-mannose for successful SLN detection in patients is safe, producing an effective dose at the level recommended for diagnostic studies (<10 mSv).

99mTc-CXCR4-L for Imaging of the Chemokine-4 Receptor Associated with Brain Tumor Invasiveness: Biokinetics, Radiation Dosimetry, and Proof of Concept in Humans.

Overexpression of the chemokine-4 receptor (CXCR4) in brain tumors is associated with high cancer cell invasiveness. Recently, we reported the preclinical evaluation of 99mTc-CXCR4-L (cyclo-D-Tyr-D-[NMe]Orn[EDDA-99mTc-6-hydrazinylnicotinyl]-Arg-NaI-Gly) as a SPECT radioligand capable of specifically detecting the CXCR4 protein. This research aimed to estimate the biokinetic behavior and radiation dosimetry of 99mTc-CXCR4-L in healthy subjects, as well as to correlate the radiotracer uptake by brain tumors in patients, with the histological grade of differentiation and CXCR4 expression evaluated by immunohistochemistry. 99mTc-CXCR4-L was obtained from freeze-dried kits prepared under GMP conditions (radiochemical purities >97%). Whole-body scans from six healthy volunteers were acquired at 0.3, 1, 2, 4, 6, and 24 h after 99mTc-CXCR4-L administration (0.37 GBq). Time-activity curves of different source organs were obtained from the image sequence to adjust the biokinetic models. The OLINDA/EXM code was employed to calculate the equivalent and effective radiation doses. Nine patients with evidence of brain tumor injury (6 primaries and 3 recurrent), determined by MRI, underwent cerebral SPECT at 3 h after administration of 99mTc-CXCR4-L (0.74 GBq). Data were expressed as a T/B (tumor uptake/background) ratio. Biopsy examinations included histological grading and anti-CXCR4 immunohistochemistry. Results showed a fast blood activity clearance (T 1/2 α = 0.81 min and T 1/2 ß = 12.19 min) with renal and hepatobiliary elimination. The average equivalent doses were 6.10E - 04, 1.41E - 04, and 3.13E - 05 mSv/MBq for the intestine, liver, and kidney, respectively. The effective dose was 3.92E - 03 mSv/MBq. SPECT was positive in 7/9 patients diagnosed as grade II oligodendroglioma (two patients), grade IV glioblastoma (two patients), grade IV gliosarcoma (one patient), metastasis, and diffuse astrocytoma with T/B ratios of 1.3, 2.3, 13, 7, 19, 5.5, and 3.9, respectively, all of them with positive immunohistochemistry. A direct relationship between the grade of differentiation and the expression of CXCR4 was found. The two negative SPECT studies showed negative immunohistochemistry with a diagnosis of reactive gliosis. This "proof-of-concept" research warrants further clinical studies to establish the usefulness of 99mTc-CXCR4-L in the diagnosis and prognosis of brain tumors.

177Lu-DOTA-HYNIC-Lys(Nal)-Urea-Glu: Biokinetics, Dosimetry, and Evaluation in Patients with Advanced Prostate Cancer.

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 177Lu-iPSMA therapeutic doses. 177Lu-iPSMA was obtained from lyophilized formulations with radiochemical purities >98%. Whole-body images from five 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 177Lu-iPSMA (3.7 or 7.4 GBq) every 8-10 weeks. Response was evaluated using the 68Ga-PSMA-ligand-PET/CT or 99mTc-iPSMA-SPECT/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 (T 1/2 α = ln2/0.614), 9.2 h for the first slow component (T 1/2 ß = ln2/0.075), and 79.6 h for the second slow component (T 1/2 γ = 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 effect of this therapeutic agent on survival of patients.

Correlación entre el volumen molecular tumoral evaluado con PET/TC con 68Ga-PSMA y los niveles de antígeno prostático específico / Correlation between molecular tumor volume evaluated with 68Ga-PSMA PET/CT and prostatic specific antigen levels

Objetivo: Investigar la asociación entre el nivel del antígeno prostático específico (PSA) en el mismo momento de la realización de PET/TC con 68Ga-PSMA y el volumen tumoral metabólico (MTV) en pacientes con cáncer de próstata en progresión bioquímica. Métodos: En este análisis retrospectivo se estudió a 84 pacientes sometidos a PET/TC con 68Ga-PSMA, a quienes se midieron los niveles de PSA en la misma semana (Trigger-PSA). Se calculó el MTV a partir de la suma de las lesiones metastásicas. Para determinar las relaciones entre el nivel de Trigger-PSA y los hallazgos de PET/TC utilizamos la correlación de Spearman. Resultados: El MTV medio de la enfermedad ósea (mBD) fue significativamente superior al valor encontrado en los ganglios metastásicos (mLN) (139,5 frente a 17,7; p<0,05). La enfermedad se limitó a la próstata en 8 pacientes (9,5%), mLN en 21 pacientes (25%), mBD en 32 pacientes (38,1%) y las 3 localizaciones (próstata, mBD y mLN) en 17 pacientes (20,2%). En 6 pacientes (6,14%), la PET/TC con 68Ga-PSMA no fue capaz de detectar la enfermedad. Los niveles medios de Trigger-PSA en los pacientes con enfermedad limitada a próstata (2,8ng/ml), mLN (6,8ng/ml) y mBD (16,8ng/ml) fueron estadísticamente significativos (p<0,05). Los pacientes positivos tuvieron un Trigger-PSA medio de 4,3ng/ml frente a 1,5ng/ml en los pacientes negativos (p<0,05). Establecimos 3 puntos límite para la tasa de detección del nivel de Trigger-PSA:≤1ng/ml (47,3%), 1-4ng/ml (68,4%) y≥4ng/ml (96,7%). Cuando el Trigger-PSA excedió de 4ng/ml, el MTV fue superior (p<0,001). Conclusión: Los resultados evidencian la correlación de MTV con Trigger-PSA, lo cual puede tener impacto sobre el tratamiento. Sin embargo, los niveles de Trigger-PSA no permitieron distinguir entre la enfermedad localizada o a distancia. La estadificación precisa de la enfermedad podría permitir planificar la mejor estrategia terapéutica

Objective: To investigate the association between prostatic-specific antigen (PSA) levels and molecular tumor volume (MTV) measured in the 68Ga-PSMA PET/CT, both done in a short period of time, in prostate cancer patients with biochemical failure. Methods: Eighty-four patients who underwent 68Ga-PSMA PET/CT and measurement of PSA levels in the same week (trigger-PSA) were studied in this retrospective analysis. MTV was calculated from the sum of the metastatic lesions. To determine the association between trigger-PSA level and PET/CT findings, Spearman rank correlation was used. Results: The median MTV of metastatic bone disease (mBD) was significantly higher than in metastatic lymph-nodes (mLN) (139.5 versus 17.7; P<.05). Disease was limited to the prostate in 8 patients (9.5%), mLN in 21 patients (25%), mBD in 32 patients (38.1%) and the 3 sites (prostate, mLN, and mBD) in 17 patients (20.2%). In 6 patients (6.14%), 68Ga-PSMA-PET/CT was not capable of detecting disease. The median trigger-PSA levels of patients with disease limited to the prostate (2.8ng/mL), mLN (6.8ng/mL), and for mBD (16.8ng/mL) was statically significant (P<.05). Positive patients had a mean trigger-PSA of 4.3ng/mL vs 1.5ng/mL in negative patients (P<.05). We established 3 threshold-points for trigger-PSA level detection rate:≤1ng/mL (47.3%), 1-4ng/mL (68.4%) and≥4ng/mL (96.7%). When trigger-PSA exceeded 4ng/mL, the MTV was higher (P<.001). Conclusion: The correlation of MTV with trigger-PSA is demonstrated, which may have an impact on management. However, trigger-PSA levels were not capable of distinguishing between localized or distant disease. An accurate detection of disease can lead to a better therapeutic strategy

Evaluation of recurrence of musculoskeletal tumors with thallium-201 scintigraphy plus SPECT/CT in pediatric population. / Evaluación de la recurrencia de tumores musculoesqueléticos mediante gammagrafía complementada con SPECT/CT con talio-201 en población pediátrica

Background: Imaging studies, particularly simple and contrast-enhanced tomography, constitute the first diagnostic approach to detect recurrence of musculoskeletal tumors. The aim of the present retrospective study was to demonstrate the usefulness of scintigraphy plus SPECT/CT (single photon emission computed tomography) with thallium-201 (201Tl) in the evaluation of malignant musculoskeletal tumors with suspicion of recurrence or metastatic disease. Methods: Eight weeks after the last therapy, 72 scintigraphy and SPECT/CT studies were performed to assess regional recurrence and metastatic disease in 42 patients with different types of malignant musculoskeletal tumors, such as osteosarcoma, Ewing's sarcoma, rhabdomyosarcoma, retinoblastoma, synovial sarcoma, and Wilms tumor at the Hospital Infantil de México Federico Gómez. The positive predictive value (PPV) and the confidence interval of the scintigraphy and SPECT/CT were calculated when compared with the results of the histopathological analysis and the clinical and radiological follow-up for the identification of recurrence. Results: Scintigraphy was abnormal in 30 (71.4%) of the 42 patients; 33 lesions (30 patients) were detected by scintigraphy and 25 lesions (21 patients) by chest X-ray and tomography of two regions. The SPECT/CT was performed on 30 patients, where 12 lesions were detected in addition to the planar scintigraphy. Scintigraphy showed a PPV of 82%; SPECT/CT, 100%. Conclusion: 201Tl-scintigraphy can be considered as an adequate study to identify the sites of tumor viability with a high degree of diagnostic certainty combined with the SPECT/CT technique.

Introducción: Los estudios de imagen, como la tomografía simple y contrastada, son la primera aproximación diagnóstica para detectar la recurrencia de tumores musculoesqueléticos. El objetivo de este estudio retrospectivo fue demostrar la utilidad de la gammagrafía acoplada a tomografía computarizada por emisión de fotón único (SPECT/CT) con talio-201(201Tl) en la valoración de tumores musculoesqueléticos malignos con sospecha de recurrencia o enfermedad metastásica. Métodos: Se realizaron 72 estudios gammagráficos y de SPECT/CT para la valoración de la recurrencia locorregional y a distancia, al menos 8 semanas tras la última terapia, en 42 pacientes con diferentes tipos de tumores musculoesqueléticos malignos, como osteosarcoma, sarcoma de Ewing, rabdomiosarcoma, retinoblastoma, sarcoma sinovial y tumor de Wilms en el Hospital Infantil de México. Se calcularon el valor predictivo positivo (VPP) y el intervalo de confianza del gammagrama y de la SPECT/CT en comparación con el resultado del análisis histopatológico y el seguimiento clínico y radiológico para identificar la recurrencia. Resultados: La gammagrafía fue anormal en 30 (71.4%) de los 42 pacientes. Se detectaron 33 lesiones (30 pacientes) por gammagrafía y 25 (21 pacientes) por telerradiografía de tórax y tomografía de dos regiones. La SPECT/CT se realizó en 30 pacientes y se detectaron 2 lesiones adicionales al rastreo planar. El VPP con la gammagrafía fue del 82%, y con la SPECT/CT, del 100%. Conclusión: La gammagrafía con 201Tl puede considerarse un estudio adecuado para identificar los sitios de viabilidad tumoral, con alto grado de certeza diagnóstica al complementar con SPECT/CT.

Correlation between molecular tumor volume evaluated with 68Ga-PSMA PET/CT and prostatic specific antigen levels. / Correlación entre el volumen molecular tumoral evaluado con PET/TC con 68Ga-PSMA y los niveles de antígeno prostático específico.

OBJECTIVE: To investigate the association between prostatic-specific antigen (PSA) levels and molecular tumor volume (MTV) measured in the 68Ga-PSMA PET/CT, both done in a short period of time, in prostate cancer patients with biochemical failure. METHODS: Eighty-four patients who underwent 68Ga-PSMA PET/CT and measurement of PSA levels in the same week (trigger-PSA) were studied in this retrospective analysis. MTV was calculated from the sum of the metastatic lesions. To determine the association between trigger-PSA level and PET/CT findings, Spearman rank correlation was used. RESULTS: The median MTV of metastatic bone disease (mBD) was significantly higher than in metastatic lymph-nodes (mLN) (139.5 versus 17.7; P<.05). Disease was limited to the prostate in 8 patients (9.5%), mLN in 21 patients (25%), mBD in 32 patients (38.1%) and the 3 sites (prostate, mLN, and mBD) in 17 patients (20.2%). In 6 patients (6.14%), 68Ga-PSMA-PET/CT was not capable of detecting disease. The median trigger-PSA levels of patients with disease limited to the prostate (2.8ng/mL), mLN (6.8ng/mL), and for mBD (16.8ng/mL) was statically significant (P<.05). Positive patients had a mean trigger-PSA of 4.3ng/mL vs 1.5ng/mL in negative patients (P<.05). We established 3 threshold-points for trigger-PSA level detection rate:≤1ng/mL (47.3%), 1-4ng/mL (68.4%) and≥4ng/mL (96.7%). When trigger-PSA exceeded 4ng/mL, the MTV was higher (P<.001). CONCLUSION: The correlation of MTV with trigger-PSA is demonstrated, which may have an impact on management. However, trigger-PSA levels were not capable of distinguishing between localized or distant disease. An accurate detection of disease can lead to a better therapeutic strategy.

Evaluación de la recurrencia de tumores musculoesqueléticos mediante gammagrafía complementada con SPECT/CT con talio-201 en población pediátrica / Evaluation of recurrence of musculoskeletal tumors with thallium-201 scintigraphy plus SPECT/CT in pediatric population

Resumen Introducción: Los estudios de imagen, como la tomografía simple y contrastada, son la primera aproximación diagnóstica para detectar la recurrencia de tumores musculoesqueléticos. El objetivo de este estudio retrospectivo fue demostrar la utilidad de la gammagrafía acoplada a tomografía computarizada por emisión de fotón único (SPECT/CT) con talio-201(201Tl) en la valoración de tumores musculoesqueléticos malignos con sospecha de recurrencia o enfermedad metastásica. Métodos: Se realizaron 72 estudios gammagráficos y de SPECT/CT para la valoración de la recurrencia locorregional y a distancia, al menos 8 semanas tras la última terapia, en 42 pacientes con diferentes tipos de tumores musculoesqueléticos malignos, como osteosarcoma, sarcoma de Ewing, rabdomiosarcoma, retinoblastoma, sarcoma sinovial y tumor de Wilms en el Hospital Infantil de México. Se calcularon el valor predictivo positivo (VPP) y el intervalo de confianza del gammagrama y de la SPECT/CT en comparación con el resultado del análisis histopatológico y el seguimiento clínico y radiológico para identificar la recurrencia. Resultados: La gammagrafía fue anormal en 30 (71.4%) de los 42 pacientes. Se detectaron 33 lesiones (30 pacientes) por gammagrafía y 25 (21 pacientes) por telerradiografía de tórax y tomografía de dos regiones. La SPECT/CT se realizó en 30 pacientes y se detectaron 12 lesiones adicionales al rastreo planar. El VPP con la gammagrafía fue del 82%, y con la SPECT/CT, del 100%. Conclusión: La gammagrafía con 201Tl puede considerarse un estudio adecuado para identificar los sitios de viabilidad tumoral, con alto grado de certeza diagnóstica al complementar con SPECT/CT.

Abstract Background: Imaging studies, particularly simple and contrast-enhanced tomography, constitute the first diagnostic approach to detect recurrence of musculoskeletal tumors. The aim of the present retrospective study was to demonstrate the usefulness of scintigraphy plus SPECT/CT (single photon emission computed tomography) with thallium-201 (201Tl) in the evaluation of malignant musculoskeletal tumors with suspicion of recurrence or metastatic disease. Methods: Eight weeks after the last therapy, 72 scintigraphy and SPECT/CT studies were performed to assess regional recurrence and metastatic disease in 42 patients with different types of malignant musculoskeletal tumors, such as osteosarcoma, Ewing's sarcoma, rhabdomyosarcoma, retinoblastoma, synovial sarcoma, and Wilms tumor at the Hospital Infantil de México Federico Gómez. The positive predictive value (PPV) and the confidence interval of the scintigraphy and SPECT/CT were calculated when compared with the results of the histopathological analysis and the clinical and radiological follow-up for the identification of recurrence. Results: Scintigraphy was abnormal in 30 (71.4%) of the 42 patients; 33 lesions (30 patients) were detected by scintigraphy and 25 lesions (21 patients) by chest X-ray and tomography of two regions. The SPECT/CT was performed on 30 patients, where 12 lesions were detected in addition to the planar scintigraphy. Scintigraphy showed a PPV of 82%; SPECT/CT, 100%. Conclusion: 201Tl-scintigraphy can be considered as an adequate study to identify the sites of tumor viability with a high degree of diagnostic certainty combined with the SPECT/CT technique.

Response Assessment of 68Ga-DOTA-E-[c(RGDfK)]2 PET/CT in Lung Adenocarcinoma Patients Treated with Nintedanib Plus Docetaxel.

Nintedanib is an oral angiokinase inhibitor used as second-line treatment for non-small cell lung cancer. New radiotracers, such as 68Ga-DOTA-E-[c(RGDfK)]2, that target αvß3 integrin might have an impact as a noninvasive method for assessing angiogenesis inhibitors. Methods: From July 2011 through October 2015, 38 patients received second-line nintedanib plus docetaxel. All patients underwent PET/CT with 68Ga-DOTA-E-[c(RGDfK)]2 radiotracer and blood-sample tests to quantify angiogenesis factors (fibroblast growth factor, vascular endothelial growth factor, and platelet-derived growth factor AB) before and after completing 2 therapy cycles. Results: Of the 38 patients, 31 had available baseline and follow-up PET/CT. Baseline lung tumor volume addressed with 68Ga-DOTA-E-[c(RGDfK)]2 PET/CT correlated with serum vascular endothelial growth factor levels, whereas baseline lung/liver SUVmax index correlated with platelet-derived growth factor AB. After treatment, the overall response rate and disease control rate were 7.9% and 47.3%, respectively. A greater decrease in lung tumor volume (-37.2% vs. -27.6%) was associated with a better disease control rate in patients (P = 0.005). Median progression-free survival was 3.7 mo. Nonsmokers and patients with a higher baseline lung tumor volume were more likely to have a higher progression-free survival (6.4 vs. 3.74 [P = 0.023] and 6.4 vs. 2.1 [P = 0.003], respectively). Overall survival was not reached. Patients with a greater decrease in lung SUVmax (not reached vs. 7.1 mo; P = 0.016) and a greater decrease in the lung/spleen SUVmax index (not reached vs. 7.1; P = 0.043) were more likely to have a longer overall survival. Conclusion:68Ga-DOTA-E-[c(RGDfK)]2 PET/CT is a potentially useful tool for assessing responses to angiogenesis inhibitors. Further analysis and novel studies are warranted to identify patients who might benefit from this therapy.

Positron emission mammography in the evaluation of interim response to neoadjuvant chemotherapy in patients with locally advanced breast cancer.

Neoadjuvant chemotherapy (NAC) has an important role in patients with locally advanced cancers, treating distant micrometastases, downstaging tumors, improving operability, and sometimes allowing breast-conserving surgery to take place. We studied the association between two Positron Emission Mammography with 18F-FDG (18F-FDG-PEM) semi-quantitative parameters in 108 patients and correlated with pathologic response in each of the following breast cancer subtype: Triple negative breast cancer (TPN), HER2-positive, and ER-positive/HER2-negative cancers. AIM: Examine the association between two Positron Emission Mammography (PEM) semi-quantitative parameters: PUVmax (maximum uptake value) and LTB (lesion to background) baseline and the end of NAC with pathologic response in each breast cancer subtype. METHODS: 108 patients, 71 with invasive ductal carcinoma and 37 with infiltrating lobular carcinoma were evaluate with 18F-FDG-PEM scans baseline and after end of NAC. We assessed the impact of 2 PEM semi-quantitative parameters for molecular subtype correlated with pathologic response according Miller-Payne grade (MPG). RESULTS: After NAC, an overall reduction of 2 PEM semi-quantitative parameters was found. Neither breast cancer subtypes nor Ki67 modified chemotherapy responses. Compared to PUVmax, an overall increase of LTB was found in baseline condition, independent of the expressed immunophenotype. Post-treatment values of PUVmax revealed a significant reduction compared to baseline values (4.8 ±â€¯0.26 vs. 1.9 ±â€¯0.18; p < 0.001) and LTB exhibited a significant decay after the first course of NACT (15.8 ±â€¯1.36 vs. 5.5 ±â€¯0.49; p < 0.001). Using the Kruskal-Wallis H test which showed no correlation between the different molecular subtypes and the MPG and PUVmax and LTB (p = 0.52), but if a correlation was found between the response rate by MPG and both semiquantitative parameters (p = 0.05). CONCLUSION: 2 PEM semi-quantitative parameters demonstrated a statically significant correlation and equivalence across the different breast cancer subtypes correlated with pathologic response according to MPG. PEM did not allow for prediction of NAC response in terms of breast cancer biomarkers, it is not discarded that this technology might be helpful for individual treatment stratification in breast cancer.

99mTc-labeled PSMA inhibitor: Biokinetics and radiation dosimetry in healthy subjects and imaging of prostate cancer tumors in patients.

The prostate-specific membrane antigen (PSMA) is expressed in epithelial cells of the prostate and highly overexpressed in 95% of advanced prostate cancers. The aims of this study was to estimate the biokinetics and dosimetry of 99mTc-EDDA/HYNIC-iPSMA (99mTc-labeled PSMA inhibitor) in eight healthy subjects and evaluate its usefulness as a tumor-imaging agent in eight prostate cancer patients. METHODS: 99mTc-EDDA/HYNIC-iPSMA was obtained from a lyophilized formulation with radiochemical purities >98%, determined by reversed-phase HPLC and ITLC-SG analyses. Whole-body images from eight healthy subjects were acquired at 20min, and at 2, 6 and 24h after 99mTc-EDDA/HYNIC-iPSMA administration. Regions of interest (ROIs) were drawn around the source organs on each time frame. Each ROI was corrected by background, attenuation, scattered radiation and physical decay. The image sequence was used to extrapolate the 99mTc-EDDA/HYNIC-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. In eight prostate cancer patients with histologically confirmed cancer, whole-body SPECT/CT images were obtained at 3h. RESULTS: The blood activity showed a half-life value of 4.98min for the fast component (T1/2α=ln2/8.34), 2.49h for the first slow component (T1/2ß=ln2/0.278), and 9.24h for the second slow component (T1/2γ=ln2/0.076). Images from patients showed an average tumor/background ratio of 8.99±3.27 at 3h. The average equivalent doses calculated for a study using 740MBq were 3.80, 7.06, 9.69, 10.70, and 28.80mSv for the breast, spleen, salivary glands, liver, and kidneys respectively, with an effective dose of 3.42±0.78mSv. CONCLUSIONS: All the absorbed doses were comparable to those known for most of the 99mTc studies. 99mTc-EDDA/HYNIC-iPSMA obtained from kit formulations showed high tumor uptake in patients with malignant lesions, making it a promising imaging radiopharmaceutical to target site-specific prostate cancer.

Clinical translation of a PSMA inhibitor for 99mTc-based SPECT.

BACKGROUND: Prostate-specific membrane antigen (PSMA) is highly over-expressed in advanced prostate cancers. 68Ga-labeled PSMA inhibitors (iPSMA) are currently used for prostate cancer detection by PET imaging. The availability of simple, efficient and reproducible radiolabeling procedures is essential for developing new SPECT radiopharmaceuticals for clinical translation. The aim of this research was to prepare 99mTc-EDDA/HYNIC-Lys(Nal)-Urea-Glu (99mTc-EDDA/HYNIC-iPSMA) obtained from lyophilized kit formulations and evaluate the in vitro and in vivo radiopharmaceutical binding to prostate cancer cells over-expressing PSMA, as well as the 99mTc-EDDA/HYNIC-iPSMA normal biodistribution in humans and the preliminary uptake in patients with prostate cancer. METHODS: 99mTc labeling was performed by adding sodium pertechnetate solution and a 0.2M phosphate buffer (pH 7.0) to a lyophilized formulation containing HYNIC-iPSMA, EDDA, tricine, mannitol and stannous chloride. The radiochemical purity was evaluated by reversed-phase HPLC and ITLC-SG analyses. Stability studies in human serum were performed by size-exclusion HPLC. In vitro cell uptake was tested using prostate cancer cells (LNCaP) with blocked and non-blocked receptors. Biodistribution and tumor uptake were determined in LNCaP tumor-bearing nude mice with blocked and non-blocked receptors, and images were obtained using a micro-SPECT/CT. Whole-body images from three healthy men and two patients with histologically-confirmed prostate cancer (one of them with a previous 68Ga-PSMA-617scan) were acquired at 1h and 3h after 99mTc-EDDA/HYNIC-iPSMA administration with radiochemical purities of >98%. RESULTS: In vitro and in vivo studies showed high radiopharmaceutical stability in human serum, specific recognition for PSMA, high tumor uptake (10.22±2.96% ID/g at 1h) with rapid blood clearance and mainly kidney elimination. Preliminary images in patients demonstrated the ability of 99mTc-EDDA/HYNIC-iPSMA to detect tumors and metastases of prostate cancer as well as 68Ga-PSMA-617 does. CONCLUSIONS: The results obtained in this study warrant further dosimetry and clinical studies to determine the specificity and sensitivity of 99mTc-EDDA/HYNIC-iPSMA.

68Ga-DTPA Anti-HER2 positron emission tomography/CT successfully predicts the overexpression of human epidermal growth factor receptor in lung metastases from breast cancer.

Molecular identification of a metastatic tumour without the inconvenience of a biopsy and the time required for pathological characterization is possible using molecular imaging. Here, we present the case of a patient with breast cancer in whom 68Ga-diethylenetriamine pentaacetic acid anti-human epidermal growth factor receptor 2 positron emission tomography-CT was successfully employed to characterize the expression of human epidermal growth factor receptor 2 in metastatic sites.

PET-Based Human Dosimetry of the Dimeric αvß3 Integrin Ligand 68Ga-DOTA-E-[c(RGDfK)]2, a Potential Tracer for Imaging Tumor Angiogenesis.

UNLABELLED: Peptides containing the Arg-Gly-Asp (RGD) sequence have high affinity for αvß3 integrin receptors overexpressed in tumor cells. The objective of this research was to determine the biodistribution and estimate the radiation dose from (68)Ga-DOTA-E-[c(RGDfK)]2 using whole-body PET scans in humans. METHODS: Five healthy volunteers (2 women, 3 men; mean age ± SD, 37.2 ± 15.6 y; range, 28-65 y; mean weight, 79.2 ± 21.0 kg; range, 64-115 kg) were included. After intravenous injection of the tracer (198.3 ± 3.3 MBq), 3 successive whole-body (vertex to mid thigh) PET/CT scans at 3 time points (30, 60, and 120 min) were obtained on a 16-slice PET/CT scanner. The subjects did not void the bladder until the entire series of images was completed. Low-dose CT without contrast agent was used for anatomic localization and attenuation correction. OLINDA/EXM software was applied to calculate human radiation doses using the reference adult model. RESULTS: The highest uptake was in the urinary bladder, followed by the liver, kidneys, and spleen, in descending order. The critical organ was the urinary bladder wall. The mean effective doses (all subjects, men and women) were 34.1 ± 4.9, 31.0 ± 2.4, and 20.9 ± 5.2 µSv/MBq for the no-voiding, 2.5-h-voiding, and 1-h-voiding models, respectively. CONCLUSION: Of particular interest in this research was the visualization of the choroid plexus and ventricular system, which seems to be a characteristic of RGD-dimeric peptides. Measured absorbed doses and effective doses are comparable to other previously reported RGD-based radiopharmaceuticals labeled with (68)Ga and (18)F. Therefore, (68)Ga-DOTA-E-[c(RGDfK)]2 can safely be used for imaging integrin αVß3 expression.