Hybrid Ga-68 prostate-specific membrane antigen PET/MRI in the detection of skeletal metastasis in patients with newly diagnosed prostate cancer: Contribution of each part to the diagnostic performance.

PURPOSE: Bone metastasis is essential in patients with prostate cancer (PCa) as it determines prognosis and survival. Hybrid PET/MRI allows simultaneous acquisition of PET and MRI data, thus combining the strength of both technologies allows the detection of bone marrow metastases that are missed by PET/CT. In this retrospective study, we aimed to evaluate the diagnostic efficiency of hybrid PET/MRI with Ga-68 prostate-specific membrane antigen (PSMA) in detecting skeletal metastases in newly diagnosed PCa patients and compared the effectiveness of stand-alone PSMA PET reviewing versus stand-alone whole-body (WB) MRI evaluation. We also investigated the effect of the interpretation of all PET/MR data together on clinical management. METHODS: We studied 74 newly diagnosed PCa patients who underwent PSMA PET/MRI for staging purposes. At first, PET and MRI were evaluated separately for bone lesions on a patient-and-lesion basis and then a further joint PSMA PET/MRI interpretation was made. RESULTS: Patient-based sensitivity, specificity, positive predictive value, negative predictive value and accuracy analysis for bone metastasis was, respectively, 1.0, 0.83, 0.54, 1.0, 0.86 for PET; 0.75, 0.96, 0.81, 0.95, 0.93 for WB MRI and 0.91, 0.95, 0.78, 0,98, 0.94 for PET/MRI. The combined PET/MRI evaluation changed the clinical impact in 13.5% of patients (eight correct and two wrong decisions) compared to PET stand-alone interpretation. CONCLUSION: PSMA PET imaging showed superior sensitivity to WB MRI in detecting bone metastases in newly diagnosed PCa patients, whereas WB MRI has superior specificity and PPV. Furthermore, the specificity and PPV of joint PET/MRI evaluation are better than PSMA PET alone. Despite the longer acquisition period, adding WB MRI sequences to PSMA PET imaging appears beneficial for PCa patient management.

99mTc-Vitamin C SPECT/CT imaging in SARS-CoV-2 associated pneumonia.

We present the first 99mTc-Vitamin C single-photon emission computed tomography/computed tomography (SPECT/CT) images obtained in patients with SARS-CoV-2 (COVID-19) infection. The CT portion of SPECT/CT images showed mostly peripheral patchy and ground-glass opacities in both lungs, which are consistent with a diagnosis of SARS-CoV-2-associated pneumonia in both patients. 99mTc-Vitamin C SPECT images showed increased tracer uptake corresponding to abnormal lung findings seen on CT in patient 1 who was newly diagnosed and treatment naïve. However, no abnormal uptake corresponding to lung CT findings was seen in patient 2 who received anti-SARS-CoV-2 treatment.

Radiopharmaceutical for detecting PSMA - positive metastatic colon cancer: Matched-pair comparison of 18F-BF3-Cy3-ACUPA and 68Ga-PSMA PET/MRI.

Prostate-specific membrane antigen (PSMA) - based radiopharmaceuticals are promising for the evaluation of PSMA-positive non-prostate cancers. In this case study, 18F-BF3-Cy3-ACUPA and 68Ga-PSMA positron emission tomography/magnetic resonance imaging (PET/MRI) were compared in a patient with metastatic colon cancer. Both 18F-BF3-Cy3-ACUPA and 68Ga-PSMA PET/MRI showed biopsy-proven metastatic left external iliac adenopathy, highlighting the feasibility of PSMA uptake in PET/MRI of metastatic nodal disease from colon cancer. Along with imaging evaluation, PSMA-based radiopharmaceuticals may also be used as a surrogate imaging tracer for potential theranostic applications using alpha or beta emitters in the context of PSMA-directed radiopharmaceutical therapy in advanced and progressive colorectal cancer.

225Actinium-labeled prostate-specific membrane antigen targeting peptide induces complete response in a metastatic prostate cancer patient.

Targeted radionuclide therapy has emerged as a promising and potentially curative strategy for high-grade prostate cancer. However, limited data are available on efficacy, quality of life, and pretherapeutic biomarkers. Here, we highlight the case of a patient with prostate-specific membrane antigen (PSMA)-positive metastatic castrate-resistant prostate cancer who displayed complete response to 225Ac-PSMA-617 after having been resistant to standard-of-care therapy, then initially partially responsive but later resistant to subsequent immunotherapy, and resistant to successive 177Lu-PSMA-617. In addition, the patient's baseline germline mutation likely predisposed him to more aggressive disease.

Evaluation of F-18 DOPA PET/CT in the detection of recurrent or metastatic medullary thyroid carcinoma: comparison with GA-68 DOTA-TATE PET/CT.

OBJECTIVE: PET imaging with F-18 DOPA (FDOPA) and Ga-68 DOTATATE (TATE) shows the most promising results to detect medullary thyroid cancer (MTC) recurrence. We performed this comparative study to detect the site of recurrent or metastatic disease in MTC patients with elevated serum calcitonin (Ctn) and/or carcinoembryonic antigen (CEA) levels. METHODS: We studied 46 MTC patients (25 women, 21 men) with elevated Ctn and/or CEA levels during follow-up who had both FDOPA and TATE PET/CT scans for re-staging purposes. RESULTS: FDOPA PET imaging yielded an overall sensitivity of 86.8%, specificity of 100%, PPV of 100%, NPV of 61.5%, and accuracy of 89.1%, while TATE PET scan had the same values as 84.2%, 87.5%, 96.9%, 53.8%, and 84.6%, respectively, and there was no statistically significant difference between the two modalities with the exception of the specificity value that was higher for FDOPA imaging. In a subgroup of patients with overt Ctn or CEA elevation, sensitivity of FDOPA increased significantly, whereas TATE sensitivity did not change. FDOPA PET imaging was significantly superior in detecting liver and regional lymph node (LN) metastases, while TATE PET scan was significantly better in the skeletal metastases. Early FDOPA demonstrated 11 invisible lesions on late FDOPA. CONCLUSION: Both FDOPA and TATE PET/CT imaging are useful to localize recurrences in MTC patients. While TATE imaging is superior to reveal skeletal disease, FDOPA seems better in liver and regional LN metastases; therefore, the two modalities appear complementary in monitoring MTC patients with elevated serum Ctn and/or CEA levels.

Small Molecule, Multimodal, [18F]-PET and Fluorescence Imaging Agent Targeting Prostate-Specific Membrane Antigen: First-in-Human Study.

BACKGROUND: A first-in-human study of [18F]-BF3-Cy3-ACUPA, a small-molecule imaging agent that can be unimolecularly both positron emitting and fluorescent, is conducted to determine its safety, biodistribution, radiation dosimetry, feasibility in tumor detection by preoperative positron emission tomography (PET), as well as its intraoperative fluorescence imaging utility in patients with prostate-specific membrane antigen positive (PSMA+) tumors. METHODS: Ten patients aged 66 ± 7 years received a 6.5 ± 3.2 mCi intravenous injection of [18F]-BF3-Cy3-ACUPA and underwent PET/computed tomography (CT) imaging. Radiation dosimetry of [18F]-BF3-Cy3-ACUPA, normal organ biodistribution, and tumor uptakes were examined. Two patients were prescheduled for radical prostatectomy (RP) with extended pelvic lymphadenectomy approximately 24 hours following [18F]-BF3-Cy3-ACUPA injection and imaging. Without reinjection, intraoperative fluorescence imaging was performed on freshly excised tissue during RP. Frozen sections of excised tissue during RP were submitted for confirmatory histopathology and multiphoton fluorescence and brightfield microscopy. RESULTS: Absorbed doses by organs including the kidneys and salivary glands were similar to 68Ga-PSMA-11 imaging. [18F]-BF3-Cy3-ACUPA physiologic radiotracer accumulation and urinary/biliary excretion closely resembled the distribution of other published PSMA tracers including [18F]-JK-PSMA-7, [18F]-PSMA-1007, [18F]-DCFPyL, and [18F]-DCFBC. 19F-BF3-Cy3-ACUPA was retained in PSMA+ cancer tissues in patients for at least 24 hours, allowing for intraoperative fluorescence assessment of the prostate and of the embedded prostate cancer without contrast reinjection. After 24 hours, the imaging agent mostly decayed or cleared from the blood pool. Preoperative PET and fluorescence imaging findings were confirmed with final histopathology and multiphoton microscopy. CONCLUSION: Our first-in-human results demonstrate that [18F]-BF3-Cy3-ACUPA is safe and feasible in humans. Larger trials with this PET tracer are expected to further define its capabilities and its clinical role in the management of PSMA+ tumors, especially in prostate cancer.

A Fluorescent, [18F]-Positron-Emitting Agent for Imaging Prostate-Specific Membrane Antigen Allows Genetic Reporting in Adoptively Transferred, Genetically Modified Cells.

Clinical trials involving genome-edited cells are growing in popularity, where CAR-T immunotherapy and CRISPR/Cas9 editing are more recognized strategies. Genetic reporters are needed to localize the molecular events inside these cells in patients. Specifically, a nonimmunogenic genetic reporter is urgently needed as current reporters are immunogenic due to derivation from nonhuman sources. Prostate-specific membrane antigen (PSMA) is potentially nonimmunogenic due to its natural, low-level expression in select tissues (self-MHC display). PSMA overexpression on human prostate adenocarcinoma is also visible with excellent contrast. We exploit these properties in a transduced, two-component, Human-Derived, Genetic, Positron-emitting, and Fluorescent (HD-GPF) reporter system. Mechanistically analogous to the luciferase and luciferin reporter, PSMA is genetically encoded into non-PSMA expressing 8505C cells and tracked with ACUPA-Cy3-BF3, a single, systemically injected small molecule that delivers positron emitting fluoride (18F) and a fluorophore (Cy3) to report on cells expressing PSMA. PSMA-lentivirus transduced tissues become visible by Cy3 fluorescence, [18F]-positron emission tomography (PET), and γ-scintillated biodistribution. HD-GPF fluorescence is visible at subcellular resolution, while a reduced PET background is achieved in vivo, due to rapid ACUPA-Cy3-BF3 renal excretion. Co-transduction with luciferase and GFP show specific advantages over popular genetic reporters in advanced murine models including, a "mosaic" model of solid-tumor intratumoral heterogeneity and a survival model for observing postsurgical recurrence. We report an advanced genetic reporter that tracks genetically modified cells in entire animals and with subcellular resolution with PET and fluorescence, respectively. This reporter system is potentially nonimmunogenic and will therefore be useful in human studies. PSMA is a biomarker of prostate adenocarcinoma and ACUPA-Cy3-BF3 potential in radical prostatectomy is demonstrated.

18F-Positron Emitting/Trimethine Cyanine-Fluorescent Contrast for Image-Guided Prostate Cancer Management.

[18/19F]-4, an anionic GCPII/PSMA inhibitor for image-guided intervention in prostate cancer, is described. [19F]-4 is radiolabeled with a radiochemical yield that is ≥27% and a molar activity of 190 ± 50 mCi/µmol in a <1 h, one-step, aqueous isotopic exchange reaction. [19F]-4 allows PSMA expression to be imaged by fluorescence (FL) and [18F]-PET. PC3-PIP (PSMA-positive, EC50 = 6.74 ± 1.33 nM) cancers are specifically delineated in mice that bear 3 million (18 mg) PC3-PIP and PC3 (control, PSMA-negative) cells. Colocalization of [18/19F]-4 PET, fluorescence, scintillated biodistribution, and PSMA expression are observed.

Utility of left lateral supine position for myocardial perfusion single-photon emission computed tomography compared with other methods of correcting inferior wall attenuation.

INTRODUCTION: Single-photon emission computed tomography (SPECT) myocardial perfusion imaging is an accepted method for reflecting the pathophysiological significance of lesions detected by coronary angiography. However, it has an inherent drawback in terms of false-positive perfusion defects for the inferior myocardial wall. To overcome this problem, different acquisition techniques have been proposed, including the computed tomographic-based attenuation correction method. In this respect, a new imaging technique, left supine lateral position SPECT myocardial perfusion imaging with technetium-99m methoxyisobutylisonitrile (Tc-99m MIBI), has been proposed to eliminate this problem and its value has been investigated in this report. MATERIALS AND METHODS: Sixty-two patients were prospectively and randomly enrolled in this study. They underwent Tc-99m MIBI SPECT in the supine, prone, left lateral, and sitting positions after an adequate stress test on the same day.The presence and extent of defects on stress images were noted in the supine image data set for the 11 myocardial segments, which were then labeled as 1 or 0 if a defect was present or absent, respectively. This evaluation sequence was repeated in all other image data sets. When defects persisted in other scan positions it was regarded as true positive, and when they were resolved they were regarded as false positive. By this means, the percentages of resolving perfusion defects by that imaging position were calculated for each observer per positional pair under comparison. RESULTS: From six interpretations carried out by the nuclear medicine physicians, 6×11×3=198 four-fold tables in 11 segments were analyzed for discrepancies between position pairs. In 31 of 33 discrepant interpretations, defects observed in any of the other positions were resolved in the lateral position. Only in two evaluations of one observer were the discrepancies against lateral positioning for the anterior wall. If the inferior wall was considered alone, it was clearly obvious that lateral positioning was more accurate than the other positions.Intraobserver evaluation showed the methodology to be highly reproducible.The SPECT findings were concordant with coronary angiography results in selected patients. CONCLUSION: Visual and quantitative evaluations of the variation in inferior wall activity lead us to suggest that SPECT imaging with Tc-99m MIBI be performed in the left lateral position to allow better visualization of the inferior and septal walls in those departments not able to utilize computed tomographic attenuation correction.

Significance of increased scrotal Tc-99m MDP uptake in patients with prostate cancer.

OBJECTIVE: We observed an unusually increased scrotal uptake as an interesting finding in some patients with prostate cancer who were scanned for any possible metastatic disease. This study was designed to investigate the significance of this incidental finding in the technetium-99m methylene diphosphonate scintigraphies. METHODS: The study population consisted of 104 patients with biopsy-proven prostate cancer (group I), 55 male patients with other cancers (group II), 30 male patients with nonmalignant diseases (group III) and finally 15 patients with benign prostate hypertrophy (group IV). The square-shaped regions of interest are placed centrally on the scrotum and then on the lateral femoral soft tissue. Then the simple ratios of the scrotal and femoral soft tissue mean counts (S/Bg) were calculated. The statistical significance of differences among the groups in terms of scrotal uptake was determined. RESULTS: Group I showed increased scrotal uptake relative to the other groups. The mean uptake ratios (S/Bg±standard deviation) were 3.49±1.42 in group I, 2.89±0.70 in group II, 2.87±0.75 in group III, and 2.91±0.60 in group IV. This ratio was significantly higher in patients with prostate cancer than the normal group (P=0.024), the group with benign prostate hypertrophy (P=0.004), and the patients with other cancers (P=0.004). CONCLUSION: Our results showed that technetium-99m methylene diphosphonate bone scintigraphy, as a routine for detecting metastatic disease or performed for other purposes, could give clues for a hidden prostate cancer. Then, in elderly male patients, we strongly recommend that it is wise to keep one's eye on scrotal activity when bone scans are read and where there is any doubt, take appropriate regions of interest to make quantitative evaluations.

The value of different washout parameters in the evaluation of renal transplants by technetium-99m-ethylene- l-l-dicysteine.

Technetium-99m-ethylene-l-l-dicysteine ((99m)Tc-EC) is an agent with a potential for renal imaging. It is reported that EC uses the same tubular transporter system as ortho-hippurate (OIH) and mercaptoacetyltriglycine (MAG3) and that this agent has good imaging properties and higher renal clearance than MAG3. In this study we used (99m)Tc-EC to compare different washout parameters in renal transplanted patients. Sixty nine scans in 55 patients (38 males, 17 females) were performed with (99m)Tc-EC during the follow-up period after kidney transplantation. After bolus injection of 280MBq (99m)Tc-EC, 60x1sec and 29x1min images were taken in anterior position. Perfusions of transplanted kidneys were examined visually and perfusion indices (PI) were calculated according to Hilson's method. The semiquantitative washout parameters such as 20 and 30min to peak activity ratios and 20 and 30min to 3min activity ratios were calculated. The patients were clinically evaluated by nephrologists experienced in renal transplantation cases and followed-up by serum creatinine and blood urea nitrogen determinants which were checked every postoperative day until stabilized to a optimal level for each patient. Two standard deviations above the mean values derived from all cases with normal functioning transplanted kidneys were calculated for each method. Then, these values served as the threshold to differentiate the pathological cases respectively. Of the 69 total studies performed, we found 34 normal kidneys, 14 rejections, 19 acute tubular necrosis (ATN) and 2 cyclosporin A toxicity cases. The number of abnormal cases detected with 30/3min, 30/max, 20/3min and 20/max indices were 27, 26, 24, and 18, respectively. In conclusion, we strongly recommend in studying renal transplants to consider the activity at the 3(rd) min post injection as a reference point instead of the time to maximum activity for washout index calculation. If, for any reason the time to maximum counts using (99m)Tc-(peak activity) is prefered, then the period of study should not be performed for less than 30min to achieve reliable results.

Intravascular radiation therapy with a Re-188 liquid-filled balloon in patients with in-stent restenosis.

OBJECTIVE: The aim of this study was to evaluate the feasibility and safety of intravascular radiation therapy (IVRT) using Re-188 filled balloon system in patients with in-stent stenosis. METHODS: A total of 39 patients with in-stent restenosis were enrolled as the IVRT (22 patients) and control groups (17 patients) of this study after a successful coronary angioplasty. For irradiation the angioplasty balloon was replaced by a noncompliant balloon of the same diameter but 10 mm longer in length with a proximal and distal radio-opaque marker to deliver the dose of 18 Gy at 0.5 mm depth from the surface of the balloon into the vessel wall. Angiographic follow-up was performed after 6 months. RESULTS: The length of the irradiated segment was between 9.14 and 22 mm and the diameter between 2.5 and 3 mm. In the IVRT group, two patients who did not receive antiplatelet therapy had myocardial infarction. Four patients who presented with stable angina earlier also had angiographically documented in-stent occlusion (two patients) and edge stenosis (two patients) of the target lesion and received angioplasty (18.1%). In the control group, three patients with recurrent angina and four asymptomatic patients had documented in-stent occlusion angiographically at 6 months and these seven patients underwent target lesion revascularization (41.2%). The overall restenosis rate in the IVRT and control groups were 23.91 and 39.86%, respectively (P=0.013). No complications were documented, except anginal pain and ST segment changes. CONCLUSION: Our results indicated that the Re-188 liquid-filled balloon is feasible, safe, and effective in patients with in-stent restenosis.