Biases in Multicenter Longitudinal PET Standardized Uptake Value Measurements

This study investigates measurement biases in longitudinal positron-emission tomography/computed tomography (PET/CT) studies that are due to instrumentation variability including human error. Improved estimation of variability between patient scans is of particular importance for assessing response to therapy and multicenter trials. We used National Institute of Standards and Technology-traceable calibration methodology for solid germanium-68/gallium-68 (⁶⁸Ge/⁶⁸Ga) sources used as surrogates for fluorine-18 (¹⁸F) in radionuclide activity calibrators. One cross-calibration kit was constructed for both dose calibrators and PET scanners using the same 9-month half-life batch of ⁶⁸Ge/⁶⁸Ga in epoxy. Repeat measurements occurred in a local network of PET imaging sites to assess standardized uptake value (SUV) errors over time for six dose calibrators from two major manufacturers and for six PET/CT scanners from three major manufacturers. Bias in activity measures by dose calibrators ranged from -50% to 9% and was relatively stable over time except at one site that modified settings between measurements. Bias in activity concentration measures by PET scanners ranged from -27% to 13% with a median of 174 days between the six repeat scans (range, 29 to 226 days). Corresponding errors in SUV measurements ranged from -20% to 47%. SUV biases were not stable over time with longitudinal differences for individual scanners ranging from -11% to 59%. Bias in SUV measurements varied over time and between scanner sites. These results suggest that attention should be paid to PET scanner calibration for longitudinal studies and use of dose calibrator and scanner cross-calibration kits could be helpful for quality assurance and control.     

The 68Ge phantom-based FDG-PET site qualification program for clinical trials adopted by FIL (Italian Foundation on Lymphoma)

PurposeThe quantitative assessment of Positron Emission Tomography (PET) scans using standardized uptake value and derived parameters proved to be superior to traditional qualitative assessment in several retrospective or mono-centric prospective reports. Since different scanners give different quantitative readings, a program for clinical trial qualification (CTQ) is mandatory to guarantee a reliable and reproducible use of quantitative PET in prospective multi-centre clinical trials and in every-day clinical life.MethodsWe set up, under the auspices of Italian Foundation on Lymphoma (FIL), a CTQ program consisting of the PET/CT scan acquisition and analysis of ¹⁸F and ⁶⁸Ge NEMA/IEC image quality phantoms for the reduction of inter-scanner variability. Variability was estimated on background activity concentration (BAC) and sphere to background ratio (SBR).ResultsThe use of a ⁶⁸Ge phantom allowed reducing the inter-scanner variability among different scanners from 74.0% to 20.5% in BAC and from 63.3% to 17.4% in SBR compared to using the ¹⁸F phantom. The CTQ criteria were fulfilled at first round in 100% and 28% of PET scanners with ⁶⁸Ge and ¹⁸F respectively.ConclusionsThe ⁶⁸Ge phantom proved a reliable tool for PET scanner qualification, able to significantly reduce the potential sources of error while increasing the reproducibility of PET derived quantitative parameter measurement.     

Production of Ga-68 with a General Electric PETtrace cyclotron by liquid target

PurposeIn recent years the use of ⁶⁸Ga (t_1/2 = 67.84 min, β⁺: 88.88%) for the labelling of different PET radiopharmaceuticals has significantly increased. This work aims to evaluate the feasibility of the production of ⁶⁸Ga via the ⁶⁸Zn(p,n)⁶⁸Ga reaction by proton irradiation of an enriched zinc solution, using a biomedical cyclotron, in order to satisfy its increasing demand.MethodsIrradiations of 1.7 M solution of ⁶⁸Zn(NO₃)₂ in 0.2 N HNO₃ were conducted with a GE PETtrace cyclotron using a slightly modified version of the liquid target used for the production of fluorine-18. The proton beam energy was degraded to 12 MeV, in order to minimize the production of ⁶⁷Ga through the ⁶⁸Zn(p,2n)⁶⁷Ga reaction. The product’s activity was measured using a calibrated activity meter and a High Purity Germanium gamma-ray detector.ResultsThe saturation yield of ⁶⁸Ga amounts to (330 ± 20) MBq/µA, corresponding to a produced activity of ⁶⁸Ga at the EOB of (4.3 ± 0.3) GBq in a typical production run at 46 µA for 32 min. The radionuclidic purity of the ⁶⁸Ga in the final product, after the separation, is within the limits of the European Pharmacopoeia (>99.9%) up to 3 h after the EOB. Radiochemical separation up to a yield not lower than 75% was obtained using an automated purification module. The enriched material recovery efficiency resulted higher than 80–90%.ConclusionsIn summary, this approach provides clinically relevant amounts of ⁶⁸Ga by cyclotron irradiation of a liquid target, as a competitive alternative to the current production through the ⁶⁸Ge/⁶⁸Ga generators.     

68Ga-DOTA and analogs: Current status and future perspectives

The construction of the ⁶⁸Ge/⁶⁸Ga generator has increased application of radiopharmaceuticals labeled with this isotope in medicine. ⁶⁸Ga-PET is widely employed in the management of neuroendocrine tumors but favorable chemistry with tri- and tetraaza-ring molecules has opened wide range of ⁶⁸Ga application in other fields of PET imaging. This review covers the radiopharmaceuticals labeled with gallium in molecular imaging and shows perspectives on the use of gallium-68 as a substitute for technetium-99, fluorine-18 and carbon-11 in some applications.     

A Generator-Produced Gallium-68 Radiopharmaceutical for PET Imaging of Myocardial Perfusion

Lipophilic cationic technetium-99m-complexes are widely used for myocardial perfusion imaging (MPI). However, inherent uncertainties in the supply chain of molybdenum-99, the parent isotope required for manufacturing ⁹⁹Mo/^99mTc generators, intensifies the need for discovery of novel MPI agents incorporating alternative radionuclides. Recently, germanium/gallium (Ge/Ga) generators capable of producing high quality ⁶⁸Ga, an isotope with excellent emission characteristics for clinical PET imaging, have emerged. Herein, we report a novel ⁶⁸Ga-complex identified through mechanism-based cell screening that holds promise as a generator-produced radiopharmaceutical for PET MPI.     

[68Ga]Ga-DO2A-(OBu-l-tyr)2: Synthesis, 68Ga-radiolabeling and in vitro studies of a novel 68Ga-DO2A-tyrosine conjugate as potential tumor tracer for PET

The synthesis, ⁶⁸Ga-labeling and in vitro study of the novel tyrosine chelate derivative [⁶⁸Ga]Ga-1,4,7,10-tetraazacyclododecane-1,7-diacetic acid-4,10-di-(O-butyl)-l-tyrosine ([⁶⁸Ga]Ga-DO₂A-(OBu-l-tyr)₂) as a potential tracer for imaging tumor metabolism by positron emission tomography (PET) is presented. This approach combines the biological amino acid transporter targeting properties of l-tyrosine with the outstanding availability of ⁶⁸Ga^III via the ⁶⁸Ge/⁶⁸Ga generator. In vitro studies utilizing the F98-glioblastoma cell line revealed specific uptake of [⁶⁸Ga]Ga-DO2A-(OBu-l-tyr)₂ that was comparable to that of the reference O-(2-[¹⁸F]fluoroethyl)-l-tyrosine (FET). These promising results indicate a high potential of [⁶⁸Ga]Ga-DO₂A-(OBu-l-tyr)₂ for molecular imaging of tumor-driven amino acid uptake by PET.     

Le DOTATOC-(68Ga) pour l’imagerie TEP des tumeurs endocrines digestives : présentation d’un cas et revue de la littérature

⁶⁸Ga is a positron emitter, obtained from a ⁶⁸Ge/⁶⁸Ga generator, which can be used to label peptides of clinical interest. DOTATOC is a tracer of high affinity for the type 2 somatostatin receptors and is used for imaging of tumours which are expressing them, including endocrine tumours. We report on the case of a patient with a history of small bowel carcinoid tumour with hepatic metastases, treated by somatostatin analogues, in whom somatostatin receptor scintigraphy showed three liver foci and DOTATOC-(⁶⁸Ga) PET/CT highlighted much more liver lesions. Two recent studies emphasised on the superiority of DOTATOC-(⁶⁸Ga) PET over somatostatin receptor scintigraphy, and its complementarity with CT, especially for the diagnosis of bone metastases. DOTATOC-(⁶⁸Ga) PET/CT, which associates the specificity of somatostatin receptor scintigraphic detection with the spatial resolution of PET and the anatomical precision of CT, seems to be promised to a brilliant future, the more so as it offers many advantages to the patient: a shorter waiting time, one single image acquisition and a satisfying dosimetry.     

Germanium-68 as a possible marker for silicon transport in rat brain

Silicon (Si) is an essential trace element normally present in brain and cerebrospinal fluid, although the mechanism by which it enters and distributes in brain is largely unknown. Due to the short radioactive half-life of³¹Si (156 min) we have investigated the use of⁶⁸Germanium (68-Ge, half-life 282 days) as a possible marker for Si transport in rat brain over longer periods than are possible with³¹Si. Adult male anaesthetised rats were given a bolus of⁶⁸Ge I. V. and arterial blood samples taken during experiments that lasted between 5 min and 3 days. At termination, the brain was removed and analysed for radioactivity as were the plasma samples. Data were analyzed by Graphical Analysis which showed that the blood-brain barrier permeability to⁶⁸Ge (K_in10^–4 ml/min/g) is similar to that for many non protein-bound electrolytes in plasma and that⁶⁸Ge fluxes across cerebral capillaries are bidirectional. The autoradiographic distribution of⁶⁸Ge in brain was homogenous. Our results are in agreement with those of previous studies using³¹Si or⁶⁸Ge, which suggest⁶⁸Ge may be a useful marker for Si when investigating the role of this element in conditions such as neurodegenerative diseases.     

68Ga-PSMA11 PET/CT for biochemically recurrent prostate cancer: Influence of dual-time and PMT- vs SiPM-based detectors

Objectives⁶⁸Ga-PSMA11 PET/CT is excellent for evaluating biochemically recurrent prostate cancer (BCR PC). Here, we compared the positivity rates of dual-time point imaging using a PET/CT scanner (DMI) with silicon photomultiplier (SiPM) detectors and a PET/CT scanner (D690) with photomultiplier tubes (PMT), in patients with BCR PC.MethodsFifty-eight patients were prospectively recruited and randomized to receive scans on DMI followed by D690 or vice-versa. Images from DMI were reconstructed using the block sequential regularized expectation maximization (BSREM) algorithm and images from D690 were reconstructed using ordered subset expectation maximization (OSEM), according to the vendor''s recommendations. Two readers independently reviewed all images in randomized order, recorded the number and location of lesions, as well as standardized uptake value (SUV) measurements.ResultsTwenty-eight patients (group A) had DMI as first scanner followed by D690, while 30 patients (group B) underwent scans in reversed order. Mean PSA was 30±112.9 (range 0.3–600.66) ng/mL for group A and 41.5 ± 213.2 (range 0.21–1170) ng/mL for group B (P = 0.796). The positivity rate in group A was 78.6% (22/28 patients) vs. 73.3% (22/30 patients) in group B. Although the performance of the two scanners was equivalent on a per-patient basis, DMI identified 5 additional sites of suspected recurrent disease when used as first scanner. The second scan time point did not reveal additional abnormal uptake.ConclusionsThe delayed time point in ⁶⁸Ga-PSMA11 PET/CT did not show a higher positivity rate. SiPM-based PET/CT identified additional lesions. Further studies with larger cohorts are needed to confirm these results.     

68Ga-labelled peptides for diagnosis of neuroendocrine tumours

On the basis of available literature, the aim of this paper is to describe the advantages and limitations of ⁶⁸Ga-DOTA peptide PET/CT imaging for the assessment of neuroendocrine tumours (NET) and to examine potential future perspectives. The introduction of new PET tracers labelled with ⁶⁸Ga has changed the diagnostic approach to NET. While in the past decades the gold standard imaging modality for NET detection was the somatostatin analogue tracers labelled with ¹¹¹In, several advantages now emerge by using both labelled somatostatin analogues with ⁶⁸Ga and PET/CT tomography for image acquisition, leading to a larger use of these tracers in clinical practice. There is an increasing number of reports showing the higher accuracy of ⁶⁸Ga-DOTA peptide PET/CT for the detection of NET lesions as compared to morphological imaging procedures and somatostatin receptor scintigraphy. The use of ⁶⁸Ga-DOTA peptides offers the possibility to non-invasively evaluate NET cells for the presence of somatostatin receptor expression, with direct therapeutic implications. Last but not least, the use of ⁶⁸Ga-DOTA peptides also leads to several practical advantages including the relatively easy and economic synthesis process and the fact that ⁶⁸Ga labelling can be performed in centres without an on-site cyclotron.     

Meningiomas: A Comparative Study of 68Ga-DOTATOC, 68Ga-DOTANOC and 68Ga-DOTATATE for Molecular Imaging in Mice

Purpose

The goal of this study was to compare the tumor uptake kinetics and diagnostic value of three ⁶⁸Ga-DOTA-labeled somatostatin analogues (⁶⁸Ga-DOTATOC, ⁶⁸Ga-DOTANOC, and ⁶⁸Ga-DOTATATE) using PET/CT in a murine model with subcutaneous meningioma xenografts.

Methods

The experiment was performed with 16 male NUDE NU/NU mice bearing xenografts of a human meningioma cell line (CH-157MN). ⁶⁸Ga-DOTATOC, ⁶⁸Ga-DOTANOC, and ⁶⁸Ga-DOTATATE were produced in a FASTLab automated platform. Imaging was performed on an Argus small-animal PET/CT scanner. The SUV_max of the liver and muscle, and the tumor-to-liver (T/L) and tumor-to-muscle (T/M) SUV ratios were computed. Kinetic analysis was performed using Logan graphical analysis for a two-tissue reversible compartmental model, and the volume of distribution (V_t) was determined.

Results

Hepatic SUV_max and V_t were significantly higher with ⁶⁸Ga-DOTANOC than with ⁶⁸Ga-DOTATOC and ⁶⁸Ga-DOTATATE. No significant differences between tracers were found for SUV_max in tumor or muscle. No differences were found in the T/L SUV ratio between ⁶⁸Ga-DOTATATE and ⁶⁸Ga-DOTATOC, both of which had a higher fraction than ⁶⁸Ga-DOTANOC. The T/M SUV ratio was significantly higher with ⁶⁸Ga-DOTATATE than with ⁶⁸Ga-DOTATOC and ⁶⁸Ga-DOTANOC. The V_t for tumor was higher with ⁶⁸Ga-DOTATATE than with ⁶⁸Ga-DOTANOC and relatively similar to that of ⁶⁸Ga-DOTATOC.

Conclusions

This study demonstrates, for the first time, the ability of the three radiolabeled somatostatin analogues tested to image a human meningioma cell line. Although V_t was relatively similar with ⁶⁸Ga-DOTATATE and ⁶⁸Ga-DOTATOC, uptake was higher with ⁶⁸Ga-DOTATATE in the tumor than with ⁶⁸Ga-DOTANOC and ⁶⁸Ga-DOTATOC, suggesting a higher diagnostic value of ⁶⁸Ga-DOTATATE for detecting meningiomas.     

Impact of 68Ga-PSMA PET/CT in the treatment of prostate cancer: Initial experience in Spain

AimTo evaluate whether positron-emission tomography/computed tomography with ⁶⁸Ga-PSMA (⁶⁸Ga-PSMA PET/CT) influences the therapeutic management of patients with primary or recurrent prostate cancer (PCa).BackgroundAlthough ⁶⁸Ga-PSMA PET/CT is one of the best options for staging or restaging patients with PCa, its availability is still very limited in Spain. The present study reports the results of the first group of patients in Spain who underwent ⁶⁸Ga-PSMA PET/CT imaging.Materials and methodsAll patients (n = 27) with a histological diagnosis of PCa who underwent ⁶⁸Ga-PSMA PET/CT prior to the definitive treatment decision at the only centre with this technology in Spain during 2017–2018 were included. Two nuclear medicine physicians and a radiologist reviewed the imaging studies. The clinical impact was assessed from a theoretical perspective, based on the treatment that would have been applied if no data from the ⁶⁸Ga-PSMA PET/CT were available.ResultsMost patients (n = 26; 96%) had persistent disease or biochemical recurrence after radical prostatectomy, radiotherapy, or combined treatment. One patient underwent ⁶⁸Ga-PSMA PET/CT imaging to stage high-risk PCa. Overall, ⁶⁸Ga-PSMA PET/CT was positive in 19 patients (70.4%). In 68.75% of these patients, none of the other imaging tests—MRI, CT, or bone scans—performed prior to the ⁶⁸Ga-PSMA PET/CT were able to detect the presence of cancerous lesions. Overall, the findings of the ⁶⁸Ga-PSMA PET/CT led to a modification of the therapeutic approach in 62.96% of the patients in the study.Conclusions⁶⁸Ga-PSMA PET/CT alters the therapeutic approach in a substantial proportion of patients with PCa.     

Convenient preparation of 68Ga-based PET-radiopharmaceuticals at room temperature

A straightforward labeling using generator produced positron emitting (68)Ga, which provides high quality images, may result in kit type production of PET radiopharmaceuticals and make PET examinations possible also at centers lacking accelerators. The introduction of macrocyclic bifunctional chelators that would provide fast (68)Ga-complexation at room temperature would simplify even further tracer preparation and open wide possibilities for (68)Ga-labeling of fragile and potent macromolecules. Gallium-68 has the potential to facilitate development of clinically practical PET and to promote PET technique for individualized medicine. The macrocyclic chelator, 1,4,7-triazacyclononanetriacetic acid (NOTA), and its derivative coupled to an eight amino acid residue peptide (NODAGA-TATE, [NODAGA (0), Tyr(3)]Octreotate) were labeled with (68)Ge/(68)Ga-generator produced positron emitting (68)Ga. Formation kinetics of (68)Ga-NOTA was studied as a function of pH and formation kinetics of (68)Ga-NODAGA-TATE was studied as a function of the bioconjugate concentration. The nearly quantitative radioactivity incorporation (RAI>95%) for (68)Ga-NOTA was achieved within less than 10 min at room temperature and pH 3.5. The concentrations of NODAGA-TATE required for RAI of >90% and >95% were, respectively, 2-5 and 10 microM. In both cases the purification of the (68)Ga-labeled products was not necessary since the radiochemical purity was >95% and the preparation buffer, 4-(2-hydroxyethyl) piperazine-1-ethanesulfonic acid (HEPES) is suitable for human use. In order to confirm the identity of the products, complexes comprising (nat)Ga were synthesized and analyzed by mass spectrometry. The complex was found to be stable in the reaction mixture, phosphate buffer, and human plasma during 4.5 h incubation. Free and peptide conjugated NOTA formed stable complexes with (68)Ga at room temperature within 10 min. This might be of special interest for the labeling of fragile and potent macromolecules and allow for kit type preparation of (68)Ga-based radiopharmaceuticals.     

Gallium-68-labeled macroaggregated human serum albumin, 68Ga-MAA

A technique is described that allows labeling of commercial MAA (macroaggregated human serum albumin) kits with generator-produced ⁶⁸Ga. This positron-emitting radiopharmaceutical should serve as an effective substitute for ⁶⁸Ga-albumin microspheres in PET imaging studies that require a particulate tracer of regional perfusion.     

Calibration Test of PET Scanners in a Multi-Centre Clinical Trial on Breast Cancer Therapy Monitoring Using 18F-FLT

A multi-centre trial using PET requires the analysis of images acquired on different systems We designed a multi-centre trial to estimate the value of 18F-FLT-PET to predict response to neoadjuvant chemotherapy in patients with newly diagnosed breast cancer. A calibration check of each PET-CT and of its peripheral devices was performed to evaluate the reliability of the results.

Material and Methods

11 centres were investigated. Dose calibrators were assessed by repeated measurements of a 68Ge certified source. The differences between the clocks associated with the dose calibrators and inherent to the PET systems were registered. The calibration of PET-CT was assessed with an homogeneous cylindrical phantom by comparing the activities per unit of volume calculated from the dose calibrator measurements with that measured on 15 Regions of Interest (ROIs) drawn on 15 consecutive slices of reconstructed filtered back-projection (FBP) images. Both repeatability of activity concentration based upon the 15 ROIs (ANOVA-test) and its accuracy were evaluated.

Results

There was no significant difference for dose calibrator measurements (median of difference −0.04%; min = −4.65%; max = +5.63%). Mismatches between the clocks were less than 2 min in all sites and thus did not require any correction, regarding the half life of 18F. For all the PET systems, ANOVA revealed no significant difference between the activity concentrations estimated from the 15 ROIs (median of difference −0.69%; min = −9.97%; max = +9.60%).

Conclusion

No major difference between the 11 centres with respect to calibration and cross-calibration was observed. The reliability of our 18F-FLT multi-centre clinical trial was therefore confirmed from the physical point of view. This type of procedure may be useful for any clinical trial involving different PET systems.     

Cyclotron vs generator-produced 68Ga PSMA: a single-institution,prospective clinical trial

The clinical utility of gallium 68 (⁶⁸Ga)-PSMA PET for the diagnosis and management of prostate cancer is driven in part by radioisotope availability and production costs. This study evaluates the equivalence between the two manufacturing processes for ⁶⁸Ga-PSMA: ⁶⁸Ga-PSMA-cyclotron (from a solid target) and ⁶⁸Ga-PSMA-generator. A prospective, single-arm, single-institution non-randomized study was conducted where 16 patients with prostate adenocarcinoma underwent PET/CTs consecutively within 12 to 48 hours with each type of manufactured ⁶⁸Ga-PSMA between December 2020 and June 2021. The intraclass correlation coefficients suggested acceptable reliability in all lesion parameters (ICC > 0.70). Bland-Altman analysis demonstrated acceptable bias levels for all lesion parameters. Thereby ⁶⁸Ga-cyclotron (solid target) and ⁶⁸Ga-generator production methods tagged to the same PSMA ligand resulted in scans which were deemed to be equivalent in detecting PSMA+ lesions in our study. As cyclotron-produced, solid- target ⁶⁸Ga can be made in large (Ci) quantities, it is a promising tool for future application in ⁶⁸Ga-PSMA PET scans with the potential to decrease radiotracer production costs and increase isotope availability.     

Accuracy of target delineation by positron emission tomography-based auto-segmentation methods after deformable image registration: A phantom study

PurposeDiagnostic positron emission tomography and computed tomography (PET/CT) images can be fused to the planning CT images by a deformable image registration (DIR). The aim of this study was to evaluate the standardized uptake value (SUV) and target delineation on deformed PET images.MethodsWe used a cylindrical phantom and removable inserts of four spheres (16–38 mm in diameter) and three ellipsoids with a volume equal to the 38-mm-diameter sphere (S38) in each. S38 was filled with 18F-fluorodeoxyglucose activity, and then PET/CT images were acquired. The contours of S38 were generated using original PET images by PET auto-segmentation (PET-AS) methods of (1) SUV2.5, (2) 40% of maximum SUV (SUV40%max), and (3) gradient-based (GB), and were deformed to the other inserts by DIR. We compared the volumes and the SUV_max with the generated contours using the deformed PET images.ResultsThe SUV_max was slightly decreased by DIR; the mean absolute difference was −0.10 ± 0.04. For SUV2.5 and SUV40%max, the differences in S38 volumes between the original and deformed PET images were less than 5%, regardless of deformation type. For the GB, the contoured volumes obtained from deformed PET images were larger than those of the original PET images for the deformation type of ellipsoids. When the S38 was deformed to the 16-mm-diameter sphere, the maximum volume difference was −22.8%.ConclusionsAlthough SUV fluctuations by DIR were negligible, the target delineation on deformed PET images by the GB should be carefully considered owing to the distortion of intensity profiles.     

Synthesis of 68Ga-labeled DOTA-nitroimidazole derivatives and their feasibilities as hypoxia imaging PET tracers

The imaging of hypoxia is important for therapeutic decision making in various diseases. (68)Ga is an important radionuclide for positron emission tomography (PET), and its usage is increasing, due to the development of the (68)Ge/(68)Ga-generator. In the present study, the authors synthesized two nitroimidazole derivatives by conjugating nitroimidazole and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) via an amide bond (4) and a thiourea bond (5). Both derivatives were labeled with (68)Ga with high labeling efficiency and were stable after labeling. The low partition coefficients (logP) of (68)Ga-4 (-4.6) and (68)Ga-5 (-4.5) demonstrated the hydrophilic natures of the derivatives, and both showed higher uptake in cancer cell lines cultured under hypoxic condition than under normoxic condition. However, (68)Ga-5 showed higher liver uptake than (68)Ga-4 in a biodistribution study due to higher lipophilicity. In an animal PET study, (68)Ga-4 showed higher standard uptake values (SUV) in tumors than (68)Ga-5 in mice xenografted with CT-26 mouse colon cancer cells.     

PSMA PET/CT to evaluate response to SBRT for prostate cancer bone metastases

BackgroundIn the current study we evaluated ⁶⁸Ga PSMA PET/ CT to measure local control of bone metastasis in oligometastatic prostate cancer patients treated with SBRT.Materials and methodsAfter the institutional review board approval, a retrospective review of medical records of consecutive prostate cancer patients treated between 2014 and 2018 was conducted. Only medical records of patients that were treated with SBRT for bone metastasis and had pre-and post-SBRT ⁶⁸Ga PSMA PET/CT scans were included in our study. Data extracted from the medical files included patient-related (age), disease-related (Gleason score, site of metastasis), and treatment-related factors and outcomes.ResultsDuring the study period, a total of 12 patients (15 lesions) were included, with a median age of 73 years. The median follow-up was 26.5 months (range 13–45 months). Median time of ⁶⁸Ga PSMA PET/ CT follow up was 17.0 months (range 3–39 months). The median pre-treatment PSA was 2 ng/mL (range 0.56–44 ng/mL) vs. post treatment PSA nadir of 0.01 ng/mL (0.01–4.32) with a median time to nadir of 7 months (range, 2–12). Local control was 93% during the follow up period and there was correlation with PS MA avidity on PE T. None patients developed recurrences in the treated bone. None of the patients had grade 3 or more toxicities during follow-up.ConclusionsSBRT is a highly effective and safe method for treatment of prostate cancer bone metastases. More studies are required to determine if SBRT provides greater clinical benefit than standard fractionation for oligometastatic prostate cancer patients. ⁶⁸Ga PSMA PET/CT should be further investigated for delineation and follow-up.     

Combination of [68Ga]Ga-PSMA PET/CT and [18F]FDG PET/CT in demonstrating dedifferentiation in castration-resistant prostate cancer

Aim of the studyIn this study, we aimed to determine the factors affecting increased glucose metabolism, which is one of the dedifferentiation mechanisms, by using [¹⁸F]FDG and [⁶⁸Ga]Ga-PSMA PET/CT in patients with castration-resistant prostate cancer (CRPC).Materials and methodNinety-three patients with CRPC were included in the study. Gleason score (GS), and total PSA and free PSA levels of the patients were recorded. Patient- and organ-based evaluations were performed according to the lesion uptakes as follows: score 0: PSMA (-) FDG (-), score 1: PSMA (+) FDG (-), score 2: PSMA (+) FDG (+) (FDG < PSMA), score 3: PSMA (+) FDG (+) (FDG = PSMA), score 4: PSMA (+) FDG (+) (FDG > PSMA), and score 5: PSMA (-) FDG (+). scores 1 and 2 were classified as group 1, and scores 3 to 5 were classified as group 2.ResultsThe median age of our patients was 70 (51–88) years. Eighty-eight patients (94.6%) were PSMA-positive, 78 patients (83.8%) were FDG-positive, and 89 patients (95.6%) were or PSMA or FDG positive. When the two groups were compared in terms of patient-based parameters, the median age and GS were found to be significantly higher in group 2. ROC analyses revealed that age and GS were significant in predicting group 2.ConclusionSince glucose metabolism can increase in CRPC patients with advanced age and high GS, we recommend combining [¹⁸F]FDG PET/CT with [⁶⁸Ga]Ga-PSMA PET/CT in routine clinical practice in order to identify this patient subset and refer them to additional therapies.