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Prostate cancer is a leading cause of cancer death in men worldwide. Imaging plays a key role in disease detection and initial staging. Emerging data has shown the superiority of PSMA imaging with PET/CT over conventional imaging for primary diagnoses. Single photon emission computed tomography is more available worldwide, and the imaging agent is low in cost. The aim of this study is to compare the diagnostic accuracy of 99m Tc-EDDA/HYNIC-iPSMA SPECT/CT to 18 F-PSMA-1007 PET/CT in the primary diagnosis of prostate cancer and the impact on clinical staging., Methods: In this prospective controlled study, 18 patients with histologically confirmed prostate cancer with unfavorable intermediate-, high-, and very high-risk characteristics were recruited to undergo 18 F-PSMA-PET/CT and 99m Tc-iPSMA SPECT/CT. The median age of the patients was 71 years old, and the median PSA level was 23.3 ng/mL. Lesions were divided into the prostate, seminal vesicles, lymph nodes, bone, and visceral metastases. Volumetric analysis was also performed between the two imaging modalities and correlated with PSA levels., Results: A total of 257 lesions were detected on 18 F-PSMA-PET/CT: prostate (n = 18), seminal vesicles (n = 12), locoregional lymph nodes (n = 62), non-locoregional (n = 67), bone (n = 90), and visceral (n = 8). Of these, 99m Tc-iPSMA-SPECT/CT detected 229 lesions, while both reviewers detected 100% of the lesions in the prostate (18/18), seminal vesicles (12/12), and visceral (8/8); LN LR (56/62; 90%), NLR (57/67; 85%), and bone (78/90; 86%). There were no statistically significant differences between volumetric parameters ( t = -0.02122; p = 0.491596)., Conclusions: 99m Tc-iPSMA SPECT/CT is useful in the primary diagnosis of prostate cancer. Despite it showing a slightly lower lesion detection rate compared to 18 F-PSMA PET/CT, it exhibited no impact on clinical staging and, consequently, the initial treatment intention.

Fibroblast activation protein (FAP) is highly expressed on the cancer-associated fibroblasts (CAF) of the tumor stroma. Recently, we reported the preclinical evaluation and clinical biokinetics of a novel 99m Tc-labeled FAP inhibitor radioligand ([ 99m Tc]Tc-iFAP). This research aimed to evaluate [ 99m Tc]Tc-iFAP for the tumor stroma imaging of six different cancerous entities and analyze them from the perspective of stromal heterogeneity. [ 99m Tc]Tc-iFAP was prepared from freeze-dried kits with a radiochemical purity of 98 ± 1%. The study included thirty-two patients diagnosed with glioma ( n = 5); adrenal cortex neuroendocrine tumor ( n = 1); and breast ( n = 21), lung ( n = 2), colorectal ( n = 1) and cervical ( n = 3) cancer. Patients with glioma had been evaluated with a previous cranial MRI scan and the rest of the patients had been involved in a [ 18 F]FDG PET/CT study. All oncological diagnoses were corroborated histopathologically. The patients underwent SPECT/CT brain imaging (glioma) or thoracoabdominal imaging 1 h after [ 99m Tc]Tc-iFAP administration (i.v., 735 ± 63 MBq). The total lesions ( n = 111) were divided into three categories: primary tumors (PT), lymph node metastases (LNm), and distant metastases (Dm). [ 99m Tc]Tc-iFAP brain imaging was positive in four high-grade WHO III-IV gliomas and negative in one treatment-naive low-grade glioma. Both [ 99m Tc]Tc-iFAP and [ 18 F]FDG detected 26 (100%) PT, although the number of positive LNm and Dm was significantly higher with [ 18 F]FDG [82 (96%)], in comparison to [ 99m Tc]Tc-iFAP imaging (35 (41%)). Peritoneal carcinomatosis lesions in a patient with recurrent colorectal cancer were only visualized with [ 99m Tc]Tc-iFAP. In patients with breast cancer, a significant positive correlation was demonstrated among [ 99m Tc]Tc-iFAP uptake values (Bq/cm 3 ) of PT and the molecular subtype, being higher for subtypes HER2+ and Luminal B HER2-enriched. Four different CAF subpopulations have previously been described for LNm of breast cancer (from CAF-S1 to CAF-S4). The only subpopulation that expresses FAP is CAF-S1, which is preferentially detected in aggressive subtypes (HER2 and triple-negative), confirming that FAP+ is a marker for poor disease prognosis. The results of this pilot clinical research show that [ 99m Tc]Tc-iFAP SPECT imaging is a promising tool in the prognostic assessment of some solid tumors, particularly breast cancer.

Neuroendocrine differentiation of prostate cancer (NEDPC) includes de novo presentation and secondary to epigenetic changes, referred as therapy-induced neuroendocrine prostate cancer (t-NEPC). Molecular imaging with prostate-specific membrane antigen (PSMA) and somatostatin analogues positron emission tomography (PET/CT) in NEDPC have not been validated. 18 F-FDG (fluorodeoxyglucose) PET/CT has numerous limitations in prostate cancer (PCa) and the utility in NEDPC has only been reported in a few series of cases. The objective of this study is to compare the lesions detection rate of the three radiotracers in metastatic t-NEPC patients. (1) Material and Methods: Retrospective evaluation of patients with prostate adenocarcinoma treated with androgen deprivation therapy, chemotherapy, a novel androgen receptor pathway inhibitor or a combination of them and a second tumour biopsy confirming t-NEPC was made. All patients underwent 18 F PSMA-1007, 18 F AlF-NOTA-Octreotide, and 18 F-FDG PET/CT. Evaluation of positive lesions was determined and SUVmax of each radiotracer was estimated and correlated with computer tomography (CT) findings. (2) Results: A total of eight patients were included. The mean time from diagnosis of prostate adenocarcinoma to t-NEPC was 28.2 months, with a mean serum specific prostate antigen (PSA) of 16.6 ng/dl at the time of NEPC diagnosis. All patients were treated with antiandrogen therapy and 87.5% with chemotherapy. A total of 273 lesions were identified by CT from which 182 were detected by 18 F-FDG PET/CT, 174 lesions by 18 F PSMA-1007, and 59 by 18 F AlF-NOTA-Octreotide. An interpatient analysis of the lesions was performed and dual tracer 18 F-FDG PET/CT and 18 F PSMA-1007 PET/CT detected a total of 270/273 lesions (98.9%). (3) Conclusions: NEDPC patients demonstrated wide inter and intrapatient molecular imaging heterogeneity within the three radiotracers. 18 F-FDG detected most lesions in t-NEPC among all radiotracers, especially in visceral sites; 18 F PSMA-1007 detected more bone lesions. 18 F AlF-NOTA-Octreotide showed no significant utility.

A standard protocol for performance evaluation of positron emission mammography (PEM) systems has not yet been established. In this work we propose a methodology based on the design of specific phantoms for this imaging modality with component dimensions in accordance with typical breast lesion sizes together with the adaptation of current international protocols designed for clinical and preclinical positron emission tomographs (PET) systems. This methodology was used to evaluate the performance of the Flex Solo II PEM scanner in terms of spatial resolution, uniformity and contrast lesion detectability, recovery coefficients and spill-over ratios. Positron range effects were studied with 18 F and 68 Ga, which have very different energy spectra. Our results indicate that in-plane spatial resolution of the system is around 3.0 mm and 4.4 mm for 18 F and 68 Ga, respectively. Lesion detectability tests with sphere diameters between 4 and 10 mm confirmed that the PEM system can resolve all the spheres (hot or cold). Percent contrast values for 18 F lie between 6%-38% and 34%-51% for hot- and cold- spheres, respectively; the corresponding intervals for 68 Ga are lower, 4%-25% and 32%-44%. Regarding uniformity quantification, the system shows percentage standard deviations within 4.9%-5.7%, while the percent background variability measurements ranged between 6.7% and 10.9% for both radionuclides. Recovery coefficients measured with hot rod diameters between 1.5 and 9 mm, have values between 0.2-1.05 and 0.17-0.69 for 18 F and 68 Ga, respectively. Spill-over ratios have large values (0.22 in average) for both radionuclides. Our results indicate that the phantoms and the methodology developed in this work can serve as the basis for establishing an image quality protocol for the systematic evaluation of PEM systems, with a potential extension for performance evaluation of dedicated breastPET scanners.

Human copper transporter 1 (hCtr1) is the main transporter of copper which has been involved as an essential cofactor in biological processes and mechanisms of action for cisplatin and its analogues. Although expression of hCtr1 is present in all tissues that require copper, several studies have showed that levels of expression are highly variable between normal and neoplastic tissues. We evaluated the potential diagnostic of the 64 CuCl 2 -PET/CT in patients with wild type non-small cell lung cancer (NSCLC). Eleven patients were included. Baseline 18 F-FDG-PET/CT and 64 CuCl 2 -PET/CT performed before to initiate treatment with platinum-based chemotherapy. 18 F-FDG-PET/CT detected a total of 68 lesions in different corporal sites: lung (24), regional lymph node (30), distant non-bone metastases (17) and bone metastases (14). Of total, 73% demonstrated high focal uptake of 64 CuCl 2 -PET/CT: 36% in primary tumor and 27% in lymph-nodes metastases. The detection-rates (DRs) was lower with 64 CuCl 2 PET/CT compared to 18 F-FDG-PET/CT, however, these was not statistically significant ( P = 0.108). A complete match was found in 2 patients. All patients were treated with platinum-based chemotherapy. According to RECIST 1.1 and PERCIST 1.0 criteria, most patients with highest uptake 64 CuCl 2 -PET/CT presented partial response (mean 3 cycles) corroborated with 18 F-FDG PET/CT. On the other hand, patients with very low uptake or faint uptake have progressive disease (3/16 patients). To our knowledge, this is the first study with 64 CuCl 2 -PET/CT in-human in patients with NSCLC chemo-naïve. Our results may represent that 64 CuCl 2 -PET/CT had a good ability for detect lesions. In addition, the 64 CuCl 2 uptake is based on the expression of Ctr1 transporters seeking to differentiate between those patients who may benefit from platinum-based therapy. More studies are necessary for confirm these findings., Competing Interests: None., (AJNMMI Copyright © 2020.)

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.

Previously, we reported the preparation and preclinical studies of 99m Tc-labeled gold nanoparticles-mannose ( 99m Tc-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 99m Tc-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 99m Tc-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 99m Tc-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 2.05 E  - 03 mSv/MBq. The mean effective residence time in SLN was 0.92 h. This preliminary study indicates that the use of 99m Tc-AuNP-mannose for successful SLN detection in patients is safe, producing an effective dose at the level recommended for diagnostic studies (<10 mSv)., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Gerardo Ramírez-Nava et al.)

Overexpression of the chemokine-4 receptor (CXCR4) in brain tumors is associated with high cancer cell invasiveness. Recently, we reported the preclinical evaluation of 99m Tc-CXCR4-L (cyclo-D-Tyr-D-[NMe]Orn[EDDA- 99m Tc-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 99m Tc-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. 99m Tc-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 99m Tc-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 99m Tc-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 β  = 12.19 min) with renal and hepatobiliary elimination. The average equivalent doses were 6.10 E  - 04, 1.41 E  - 04, and 3.13 E  - 05 mSv/MBq for the intestine, liver, and kidney, respectively. The effective dose was 3.92 E  - 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 99m Tc-CXCR4-L in the diagnosis and prognosis of brain tumors., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Paola Vallejo-Armenta et al.)

SPECT/CT images in patients have demonstrated the ability of [ 99m Tc]Tc-EDDA/HYNIC-Lys(Nal)-Urea-Glu ([ 99m Tc]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 177 Lu-DOTA-HYNIC-Lys(Nal)-Urea-Glu ( 177 Lu-iPSMA) in healthy subjects and analyze the response in patients receiving 177 Lu-iPSMA therapeutic doses. 177 Lu-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 177 Lu-iPSMA administration (185 MBq). The image sequence was used to extrapolate the 177 Lu-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 177 Lu-iPSMA (3.7 or 7.4 GBq) every 8-10 weeks. Response was evaluated using the 68 Ga-PSMA-ligand-PET/CT or 99m Tc-iPSMA-SPECT/CT diagnostic images and serum PSA levels before and after 177 Lu-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 β = 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. 177 Lu-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.

Positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) has found widespread use for the diagnosis of biochemical recurrence of prostate cancer (PCa). Unfortunately, PET/CT is not as widely available; thus a PSMA-targeting compound for scintigraphy is of special interest. The aim of this study was to compare 99m Tc-EDDA/HYNIC-iPSMA and 68 Ga-PSMA-11 PET/CT qualitatively and semi-quantitatively. Twenty-three patients with metastatic PCa were underwent 99m Tc-EDDA/HYNIC-iPSMA SPECT/CT followed by 68 Ga-PSMA-11 PET/CT. Gleason score in all patients was obtained. Maximal standardized uptake value (SUVmax) and counts per organ, including the primary and metastatic tumor, were normalized and compared using Pearson's correlation test. Sites considered as positive have increased SUVmax and tumor-to-background ratio (TBR) in comparison with non-diseased organs/tissues (SUVmax =25.2±4.7, 18.4±1.6, 11.4±1.2 (P=0.037) from prostate, bone and lymph nodes versus TBR =35.9±45.2, 15.4±18.9, 19.1±51.7 (P=0.035) for prostate, bone and lymph nodes. 99m Tc-HYNIC-iPSMA and 68 Ga-PSMA-11 uptake values in the evaluation of the affected nodes were very similar, although their ranges ranged from 5-21 mm (12±7.6). Correlation coefficient was normalized between SUVmax and TBR, demonstrating r values for prostate of r 2 =0.731; for bone of r 2 =0.720; and lymph nodes of r 2 =0.864 (P<0.05 in all cases). Values and confidence interval at the 95% are supporting the equivalency of both parameters in primary tumor and metastases (prostate 95% CI=4.61, 4.38; bone tissue 95% CI=-2.21, 3.41 and lymph node 95% CI=4.67). We conclude that 68 Ga-PSMA-11 PET/CT and 99m Tc-EDDA/HYNIC-iPSMA SPECT/CT were comparable, supporting the use of 99m Tc-EDDA/HYNIC-iPSMA in patients with progressive metastatic castration-resistant PCa., Competing Interests: None.

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 ( 201 Tl) 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: 201 Tl-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., (Copyright: © 2018 Permanyer.)

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 18 F-FDG ( 18 F-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 18 F-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 ± 0.26 vs. 1.9 ± 0.18; p < 0.001) and LTB exhibited a significant decay after the first course of NACT (15.8 ± 1.36 vs. 5.5 ± 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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: In recent years, Copper-64 (T 1/2  = 12.7 h) in the chemical form of copper dichloride ([ 64 Cu]CuCl 2 ) has been identified as a potential agent for PET imaging and radionuclide therapy targeting the human copper transporter 1, which is overexpressed in a variety of cancer cells. Limited human biodistribution and radiation dosimetry data is available for this tracer. The aim of this research was to determine the biodistribution and estimate the radiation dosimetry of [ 64 Cu]CuCl 2 , using whole-body (WB) PET scans in healthy volunteers. Six healthy volunteers were included in this study (3 women and 3 men, mean age ± SD, 54.3 ± 8.6 years; mean weight ± SD, 77.2 ± 12.4 kg). After intravenous injection of the tracer (4.0 MBq/kg), three consecutive WB emission scans were acquired at 5, 30, and 60 min after injection. Additional scans were acquired at 5, 9, and 24 h post-injection. Low-dose CT scan without contrast was used for anatomic localization and attenuation correction. OLINDA/EXM software was used to calculate human radiation doses using the reference adult model., Results: The highest uptake was in the liver, followed by lower and upper large intestine walls, and pancreas, in descending order. Urinary excretion was negligible. The critical organ was liver with a mean absorbed dose of 310 ± 67 μGy/MBq for men and 421 ± 56 μGy/MBq for women, while the mean WB effective doses were 51.2 ± 3.0 and 61.8 ± 5.2 μSv/MBq for men and women, respectively., Conclusions: To the best of our knowledge, this is the first report on biodistribution and radiation dosimetry of [ 64 Cu]CuCl 2 in healthy volunteers. Measured absorbed doses and effective doses are higher than previously reported doses estimated with biodistribution data from patients with prostate cancer, a difference that could be explained not just due to altered biodistribution in cancer patients compared to healthy volunteers but most likely due to the differences in the analysis technique and assumptions in the dose calculation.

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 99m Tc-EDDA/HYNIC-iPSMA ( 99m Tc-labeled PSMA inhibitor) in eight healthy subjects and evaluate its usefulness as a tumor-imaging agent in eight prostate cancer patients., Methods: 99m Tc-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 99m Tc-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 99m Tc-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 (T 1/2 α=ln2/8.34), 2.49h for the first slow component (T 1/2 β=ln2/0.278), and 9.24h for the second slow component (T 1/2 γ=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 99m Tc studies. 99m Tc-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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Prostate-specific membrane antigen (PSMA) is highly over-expressed in advanced prostate cancers. 68 Ga-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 99m Tc-EDDA/HYNIC-Lys(Nal)-Urea-Glu ( 99m Tc-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 99m Tc-EDDA/HYNIC-iPSMA normal biodistribution in humans and the preliminary uptake in patients with prostate cancer., Methods: 99m Tc 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 68 Ga-PSMA-617scan) were acquired at 1h and 3h after 99m Tc-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 99m Tc-EDDA/HYNIC-iPSMA to detect tumors and metastases of prostate cancer as well as 68 Ga-PSMA-617 does., Conclusions: The results obtained in this study warrant further dosimetry and clinical studies to determine the specificity and sensitivity of 99m Tc-EDDA/HYNIC-iPSMA., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To determine the effectiveness of therapy with the radiolabelled somatostatin analogues, 90 Y-DOTATOC and 177 Lu-DOTATATE, in the treatment of metastatic neuroendocrine tumours with progression to first-line treatment., Material and Methods: A study was conducted on 30 patients diagnosed with neuroendocrine tumours (gastroenteropancreatic, bronchopulmonary, MEN2A, MEN2B, phaeochromocytoma, and paraganglioma) with metastatic disease diagnosed by the pathology department, with progression to first-line treatment, and recruited from December 2014 to February 2016. Efficacy was analysed using computed tomography (CT) according RECIST 1.1 criteria, and the molecular changes using the SUVmax of PET/CT with 68 Ga-DOTATOC. Safety was carried out with a renal scan with 99m Tc-MAG3., Results: The 30 patients received a total of 49 cycles 90 Y-DOTATOC (21 doses) and 177 Lu-DOTATATE (28 doses), with a mean of 1.5 cycles per patient. Of these, 17 (56.7%) showed a partial morphological response, 22 (73.3%) molecular and biochemical response, and 23 (76.6%) clinical response. One patient died during the median follow-up of 13 months. The median overall survival from diagnosis was 54 months (95% CI; 31.18-76.81), and median progression-free survival was 32 months (95% CI; 15.00-48.99)., Conclusion: Therapy with 90 Y-DOTATOC and 177 Lu-DOTATATE is a promising therapy for patients with well and moderately differentiated neuroendocrine tumours. The efficacy is better the larger the number of cycles administered, inversely proportional to the number of metastases (<10), and is associated with the level of uptake according to the SUVmax by the metastases, regardless of metabolically active tumour volume., (Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.)

Unlabelled: Peptides containing the Arg-Gly-Asp (RGD) sequence have high affinity for αvβ3 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 αVβ3 expression., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)