Exploring the Potential Value of [68Ga]Ga-FAPI-46 PET/CT for Molecular Assessment of Fibroblast Activation in Interstitial Lung Disease: A Single-Center Pilot Study.

BACKGROUND: The aim of the study was to evaluate the association of high-resolution computed tomography (HRCT) findings with pulmonary fibrotic activity in the corresponding regions using [68Ga]Ga-fibroblast activation fibroblast inhibitor (FAPI) PET/CT in patients with interstitial lung disease (ILD). Additionally, the potential of [68Ga]Ga-FAPI-46 PET/CT for evaluating the active fibrosis process and 99mTc-MIBI scintigraphy for assessing the inflammatory process in ILD patients was also assessed. METHODS: In this pilot study, 20 ILD patients underwent [68Ga]Ga-FAPI-46 PET/CT and 99mTc-MIBI SPECT/CT. Additionally, 10 patients without lung or thoracic involvement who were undergoing [68Ga]Ga-FAPI PET/CT for cancer detection were enrolled in the control group. The images were evaluated both visually and semiquantitatively and also compared with HRCT and pulmonary function tests. Multiple quantitative parameters were derived from the lung segments in the PET scan, including SUVmax, SUVmean, maximum target-to-liver ratio, mean target-to-liver ratio (TLRmean), and total lesion FAPI expression for the entire lung, as well as its lobes and zones. Additionally, the maximum Hounsfield unit (HU) and mean HU in HRCT were calculated for the whole lung as well as its lobes and zones. Furthermore, an HRCT fibrosis score (HFS) was defined according to the HRCT findings. RESULTS: Twenty ILD patients with a mean age of 58.70 (SD, 11.09) years were enrolled. Additionally, 10 control patients were enrolled with a mean age of 57.70 (SD, 15.19) years. Based on visual assessment, the FAPI scan was positive in 12 (60%) patients. Similarly, the MIBI scan was positive in 12 (60%) patients. In the 20 ILD cases, both scans were positive in 6 cases, and both were negative in 2 cases. Six cases showed FAPI-negative and MIBI-positive results, whereas another 6 cases showed FAPI-positive and MIBI-negative results. Comparing the control and ILD patients, there was a significant difference in SUVmax, SUVmean, total lesion FAPI expression, TLRmean, maximum HU, and mean HU (P < 0.05). When comparing HFS with PET-derived parameters in zones, a significant positive correlation was found between HFS and SUVmean, SUVmax, maximum target-to-liver ratio, and TLRmean (P < 0.05). Additionally, a significant difference was noted between FAPI results and HFS (P = 0.003). An ancillary finding, 9 of 20 (45%) ILD patients showed intense FAPI uptakes in gallbladder, whereas none of the 10 in the control group showed such uptake. CONCLUSION: The present study may suggest that combining [68Ga]Ga-FAPI PET/CT and 99mTc-MIBI SPECT/CT yields an additive effect for evaluating ILD-related fibrosis and inflammatory processes over using either modality alone. Furthermore, it appears that [68Ga]Ga-FAPI PET/CT has the potential to ascertain levels of fibrotic activity from population of resident fibroblasts, active fibroblasts, and scar maturation among ILD patients based on their HRCT patterns.

Exploring innovative strides in radiolabeled nanoparticle progress for multimodality cancer imaging and theranostic applications.

Multimodal imaging unfolds as an innovative approach that synergistically employs a spectrum of imaging techniques either simultaneously or sequentially. The integration of computed tomography (CT), magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and optical imaging (OI) results in a comprehensive and complementary understanding of complex biological processes. This innovative approach combines the strengths of each method and overcoming their individual limitations. By harmoniously blending data from these modalities, it significantly improves the accuracy of cancer diagnosis and aids in treatment decision-making processes. Nanoparticles possess a high potential for facile functionalization with radioactive isotopes and a wide array of contrast agents. This strategic modification serves to augment signal amplification, significantly enhance image sensitivity, and elevate contrast indices. Such tailored nanoparticles constructs exhibit a promising avenue for advancing imaging modalities in both preclinical and clinical setting. Furthermore, nanoparticles function as a unified nanoplatform for the co-localization of imaging agents and therapeutic payloads, thereby optimizing the efficiency of cancer management strategies. Consequently, radiolabeled nanoparticles exhibit substantial potential in driving forward the realms of multimodal imaging and theranostic applications. This review discusses the potential applications of molecular imaging in cancer diagnosis, the utilization of nanotechnology-based radiolabeled materials in multimodal imaging and theranostic applications, as well as recent advancements in this field. It also highlights challenges including cytotoxicity and regulatory compliance, essential considerations for effective clinical translation of nanoradiopharmaceuticals in multimodal imaging and theranostic applications.

Prognostic Significance of Baseline Clinical and [68Ga]Ga-PSMA PET Derived Parameters on Biochemical Response, Overall Survival, and PSA Progression-Free Survival in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients Undergoing [177Lu]Lu-PSMA Therapy.

BACKGROUND: In this study, we sought to identify the clinical baseline characteristics and pre-therapy 68Ga-PSMA PET derived parameters that can have impact on PSA (biochemical) response, OS and PSA PFS in patients with metastatic castration-resistant prostate cancer (mCRPC) who undergo RLT with [177Lu]Lu-PSMA-617. METHODS: Various pre-treatment clinical and PSMA PET derived parameters were gathered and computed. We used PSA response as the criteria for more than a 50% decrease in PSA level, and OS and PSA PFS as endpoints. We assessed the collected parameters in relation to PSA response. Additionally, we employed univariable Cox regression and Kaplan-Meier analysis with log rank to evaluate the influence of the parameters on OS and PFS. RESULTS: A total of 125 mCRPC patients were included in this study. The median age was 68 years (range: 49-89). Among the cases, 77 patients (62%) showed PSARS, while 48 patients (38%) did not show PSA response. The median OS was 14 months (range: 1-60), and the median PSA-PFS was 10 months (range: 1-56). Age, prior history of chemotherapy, and SUVmax had a significant impact on PSA response (p<0.05). PSA response, RBC count, hemoglobin, hematocrit, neutrophil to lymphocyte ratio (NLR), alkaline phosphatase (ALP), number of metastases, wbPSMA-TV, and wbTL-PSMA significantly affected OS. GS, platelet count, NLR, and number of metastases were found to have a significant impact on PSA PFS. CONCLUSION: We have identified several baseline clinical and PSMA PET derived parameters that can serve as prognostic factors for predicting PSA response, OS, and PSA PFS after RLT. Based on the findings, we believe that these clinical baseline characteristics can assist nuclear medicine specialists in identifying RLT responders who have long-term survival and PFS.

Prostate Cancer Theranostics With 177Lu-PSMA.

This review paper highlights the transformative role of PSMA-targeted diagnostics and therapy in prostate cancer management, particularly focusing on 177Lu-PSMA-617, approved by the FDA and EMA for metastatic castration-resistant prostate cancer (mCRPC) patients post-chemotherapy and ARPI treatment. Originating from the VISION trial's success, this paper navigates the current radioligand therapy (RLT) indications, emphasizing practical patient selection, planning, and treatment execution. It critically examines Lu-PSMA's comparative effectiveness against cabazitaxel and Ra-223, addressing decision-making dilemmas for mCRPC treatments. Furthermore, the paper discusses Lu-PSMA in chemotherapy-naïve patients and its application in hormone-sensitive prostate cancer, underlined by ongoing global studies. A significant concern is Lu-PSMA's long-term safety profile, particularly nephrotoxicity risks, necessitating further investigation. The possibility of Lu-PSMA rechallenge in responsive patients is explored, stressing the need for comprehensive analyses and real-world data to refine treatment protocols. Conclusively, PSMA-targeted therapy marks a significant advance in prostate cancer therapy, advocating for its integration into a multimodal, patient-centric treatment approach. The review underscores the imperative for additional comparative studies to optimize treatment sequences and outcomes, ultimately enhancing long-term prognosis and disease control in prostate cancer management.

Optimal Indications of Radioimmunotherapy in Nuclear Medicine: A Mini-Review.

Immunotherapy has emerged as a very considerable and potent therapeutic method in which immune inhibitors have gained a lot of attention in the curative field of various cancers. Under certain circumstances, when radiotherapy is accompanied by immunotherapy, the efficacy of the therapeutic procedure increases. Irradiated tumor cells follow a pathway called immunogenic cell death, which targets tumor associated antigens. The application of radiolabeled antibodies under the concept of "radioimmunotherapy" (RIT) makes the synergistic targeted therapeutic effect possible. Since antibodies themselves are cytotoxic, they can kill the cells that not only bind but are within the path length of their radiation emissions. RIT can be categorized as a substantial progress in nuclear medicine. The main concept of RIT includes targeting specified tumor-expressing antibodies. The mentioned purpose is achievable by formulation of radiolabeled antibodies, which could be injected intravenously or directly into the tumor, as well as compartmentally into a body cavity such as the peritoneum, pleura, or intrathecal space. RIT has demonstrated very optimistic therapeutic outcomes in radioresistant solid tumors. Wide ranges of efforts are accomplished in order to improve clinical trial accomplishments. In this review, we intend to summarize the performed studies on RIT and their importance in medicine.

Pain Outcomes in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with 223Ra: PARABO, a Prospective, Noninterventional Study.

223Ra, a targeted α-therapy, is approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who have bone metastases. In the phase 3 ALSYMPCA study, 223Ra prolonged survival and improved quality of life versus placebo. Our real-world study, PARABO, investigated pain and bone pain-related quality of life in patients with mCRPC and symptomatic bone metastases receiving 223Ra in clinical practice. Methods: PARABO was a prospective, observational, noninterventional single-arm study conducted in nuclear medicine centers across Germany (NCT02398526). The primary endpoint was a clinically meaningful pain response (≥2-point improvement from baseline for the worst-pain item score in the Brief Pain Inventory-Short Form). Results: The analysis included 354 patients, who received a median of 6 223Ra injections (range, 1-6). Sixty-seven percent (236/354) received 5-6 injections, and 33% (118/354) received 1-4 injections. Of 216 patients with a baseline worst-pain score of more than 1, 59% (128) had a clinically meaningful pain response during treatment. Corresponding rates were 67% (range, 98/146) with 5-6 223Ra injections versus 43% (range, 30/70) with 1-4 injections, 60% (range, 60/100) in patients with no more than 20 lesions versus 59% (range, 65/111) in those with more than 20 lesions, and 65% (range, 69/106) in patients without prior or concomitant opioid use versus 54% (range, 59/110) in those with prior or concomitant opioid use. Mean subscale scores (pain severity and pain interference) on the Brief Pain Inventory-Short Form improved during treatment. Conclusion: 223Ra reduced pain in patients with mCRPC and symptomatic bone metastases, particularly in patients who received 5-6 injections. The extent of metastatic disease did not impact pain response.

Potential Role of Somatostatin Receptor Scintigraphy for In Vivo Imaging of Vulnerable Atherosclerotic Plaques and Its Association with Myocardial Perfusion Imaging Finding: A Preliminary Study.

Objectives: This study was conducted to detect atherosclerotic plaques with somatostatin receptor scintigraphy (SRS) using Tc-99m-octreotide that binds to somatostatin receptor-2. Methods: Of the 783 patients referred for myocardial perfusion imaging (MPI), 52 underwent additional chest single-photon emission computed tomography (SPECT) with Tc-99m-octreotide and participated in this study. In addition, 43 patients who underwent Tc-99m-octreotide scan for neuroendocrine tumor (NET) also received cardiac SPECT. Angiography was performed within 1 month after SRS for 19 patients who showed intensive uptake in SRS and had cardiac risk factors. Results: Of 52 patients who underwent MPI and SRS, 15 showed intensive cardiac uptake in SRS. Moreover, of 43 patients who were referred for NET, 4 patients had marked cardiac uptake in SRS in the heart. Nineteen patients including 12 women and 7 men aged 28 to 84 (58±8.04) years underwent coronary angiography. SRS and angiography in the left anterior descending territory were concordant in 15/19 (79%) patients, whereas only 7/15 (46%) cases had concordant MPI and angiography results. In the right coronary artery territory, SRS and angiography were concordant in 16/19 (84%) cases, while MPI and angiography were concordant in 11/15 (73%) cases. In the left circumflex artery territory, SRS and angiography were concordant in 15/19 (79%) cases, whereas MPI and angiography were concordant in 6/15 (40%) cases. In the remaining 76 patients who did not undergo coronary angiography based on cardiovascular profile and SRS, no cardiac events occurred in a follow-up of 2-11 months (7.52±2.71). Conclusion: Tc-99m-octreotide uptake was more concordant with coronary plaques relative to MPI findings, suggesting a potential role for Tc-99m-octreotide in the evaluation of atherosclerosis.

Clinical Translation of Targeted α-Therapy: An Evolution or a Revolution?

The field of radioligand therapy has advanced greatly in recent years, driven largely by ß-emitting therapies targeting somatostatin receptor-expressing tumors and the prostate-specific membrane antigen. Now, more clinical trials are under way to evaluate α-emitting targeted therapies as potential next-generation theranostics with even higher efficacy due to their high linear energy and short range in human tissues. In this review, we summarize the important studies ranging from the first Food and Drug Administration-approved α-therapy, 223Ra-dichloride, for treatment of bone metastases in castration-resistant prostate cancer, including concepts in clinical translation such as targeted α-peptide receptor radiotherapy and 225Ac-PSMA-617 for treatment of prostate cancer, innovative therapeutic models evaluating new targets, and combination therapies. Targeted α-therapy is one of the most promising fields in novel targeted cancer therapy, with several early- and late-stage clinical trials for neuroendocrine tumors and metastatic prostate cancer already in progress, along with significant interest and investment in additional early-phase studies. Together, these studies will help us understand the short- and long-term toxicity of targeted α-therapy and potentially identify suitable therapeutic combination partners.

[Procedure Guideline for Prostate Cancer Imaging with PSMA-ligand PET/CT]. / DGN-Handlungsempfehlung (S1-Leitlinie) ­ PSMA-Liganden-PET/CT in der Diagnostik des Prostatakarzinoms ­ Stand: 01/2022 ­ AWMF-Registernummer: 031-055.

PSMA-PET/CT for imaging prostate cancer (PC) has spread worldwide since its clinical introduction in 2011. The majority of experiences have been collected for PSMA-PET-imaging of recurrent PC. Data for primary staging of high-risk PC are highly promising. Meanwhile, a plethora of PSMA-ligands are available for clinical use (e. g. 68Ga-PSMA-11, 68Ga-PSMA-I&T, 68Ga-PSMA-617, 18F-DCFBC, 18F-DCFPyL, 18F-PSMA-1007, 18F-rhPSMA-7 and 18F-JK-PSMA-7). However, an official approval is available only for 68Ga-PSMA-11 (approved by the US FDA in 2020) and 18F-DCFPyL (approved by the US FDA in 2021).Recommendations for acquisition times vary from 1-2 h p. i. It has been shown that for the majority of tumour lesions, the contrast in PSMA-PET/CT increases with time. Therefore, additional late imaging can help to clarify unclear findings. PSMA-PET/CT should be performed prior to commencing an androgen deprivation therapy (ADT) since (long term) ADT reduces the visibility of PC lesions. Following injection of PSMA-ligands, hydration and forced diuresis are recommended for PSMA-ligands with primarily excretion via the kidneys in order to increase the visibility of tumour lesions adjacent to the urinary bladder.PSMA-ligands are physiologically taken up in multiple normal organs. For some 18F-labelled PSMA-ligands, presence of unspecific focal bone uptake has been reported. When using these tracers, focal bone uptake without CT-correlate should be interpreted with great caution. Besides prostate cancer, practically all solid tumors express PSMA in their neovasculature thereby taking up PSMA-ligands, although usually at a lower extent compared to PC. Also multiple benign lesions and inflammatory processes (e. g. lymph nodes) take up PSMA-ligands, also usually at lower extent compared to PC.

Adoption of Lutetium-177 PSMA radioligand therapy for metastatic castration resistant prostate cancer: a total population analysis in Germany from 2016 to 2020.

PURPOSE: This study is to investigate the adoption and current trends of Lutetium-177 PSMA RLT for mCRPC in Germany. METHODS: We analyzed data from the reimbursement.INFO tool based on German hospitals' quality reports for Lutetium-177 PSMA RLT from 2016 to 2020 and from the nationwide German hospital billing database (Destatis) for general therapy with open radionuclides in combination with prostate cancer from 2006 to 2020. For validation of these billing data, we included the 177Lu-PSMA RLT cycles from two participating institutions from 2016 to 2020. For detection of trends over time we applied linear regression models. RESULTS: General therapy with open radionuclides increased from 2006 to 2020. We identified a total of 12,553 177Lu-PSMA RLT cycles. The number of 177Lu-PSMA RLTs steadily increased from a total of 1026 therapies in 2016 to 3328 therapies in 2020 (+ 576 RLT/year; p < 0.005). In 2016, 25 departments of nuclear medicine offered this treatment, which increased to 44 nuclear medicine departments in 2020. In 2016, 16% of nuclear medicine departments (4/25) performed more than 100 177Lu-PSMA RLTs, which increased to 36% (16/44) in 2020 (p < 0.005). In 2016, 88% (22/25) of 177Lu-PSMA RLTs were performed at a university hospital, which decreased to 70% (31/44) in 2020. The proportion of patients older than 65 years receiving 177Lu-PSMA RLT increased from 78% in 2016 to 81% in 2020. CONCLUSION: Treatment of mCRPC with 177Lu-PSMA RLT has been rapidly increasing in Germany in the recent years providing an additional therapy option. This development is remarkable, because of outstanding formal EMA approval.

Feasibility and therapeutic potential of the 68Ga/177Lu-DOTATATE theranostic pair in patients with metastatic medullary thyroid carcinoma.

BACKGROUND: This study assessed: 1) the clinical efficacy of imaging with 68Ga-DOTATATE PET/CT (SSTR (somatostatin receptor)-PET) to detect medullary thyroid carcinoma (MTC); and 2) the therapeutic efficacy of peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE in MTC patients. MATERIALS AND METHODS: Patients with histologically proven MTC and suspected recurrence following thyroidectomy, based on raised serum calcitonin levels, underwent SSTR-PET. In addition, to evaluate the clinical efficacy and safety of PRRT, the patients with intense uptake on SSTR-PET or 99mTc-octreotide scintigraphy underwent PRRT. The Common Terminology Criteria for Adverse Events (version 4.03) was used to grade adverse events after PRRT. Treatment response was classified as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). RESULTS: Twenty MTC patients (10 male, 10 female) with a median age of 48.5 years underwent SSTR-PET. SSTR-PET was positive in 17/20 patients (85%). Four of the 17 patients with positive SSTR-PET were scheduled for PRRT. In addition, 2 patients had positive 99mTc-octreotide scintigraphy results (Krenning score ≥ 2) and were scheduled for PRRT. Two of the 6 patients who underwent PRRT showed PR, 2 SD and 2 PD. Two patients died during the follow-up period. Median overall survival was 19 months (95% CI: 5.52-29.48). There were no cases of significant toxicity. CONCLUSION: Radiolabeled somatostatin analogs are contributive for the management of recurrent MTC. 68Ga-DOTATAE PET-CT showed a relatively high detection rate in recurrent MTC. In addition, PRRT with 177Lu-DOTATATE was found to be a safe alternative therapeutic option for MTC.

Multicentric 68Ga-PSMA PET radiomics for treatment response assessment of 177Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer.

Objective: The treatment with 177Lutetium PSMA (177Lu-PSMA) in patients with metastatic castration-resistant prostate cancer (mCRPC) has recently been approved by the FDA and EMA. Since treatment success is highly variable between patients, the prediction of treatment response and identification of short- and long-term survivors after treatment could help tailor mCRPC diagnosis and treatment accordingly. The aim of this study is to investigate the value of radiomic parameters extracted from pretreatment 68Ga-PSMA PET images for the prediction of treatment response. Methods: A total of 45 mCRPC patients treated with 177Lu-PSMA-617 from two university hospital centers were retrospectively reviewed for this study. Radiomic features were extracted from the volumetric segmentations of metastases in the bone. A random forest model was trained and validated to predict treatment response based on age and conventionally used PET parameters, radiomic features and combinations thereof. Further, overall survival was predicted by using the identified radiomic signature and compared to a Cox regression model based on age and PET parameters. Results: The machine learning model based on a combined radiomic signature of three features and patient age achieved an AUC of 0.82 in 5-fold cross-validation and outperformed models based on age and PET parameters or radiomic features (AUC, 0.75 and 0.76, respectively). A Cox regression model based on this radiomic signature showed the best performance to predict overall survival (C-index, 0.67). Conclusion: Our results demonstrate that a machine learning model to predict response to 177Lu-PSMA treatment based on a combination of radiomics and patient age outperforms a model based on age and PET parameters. Moreover, the identified radiomic signature based on pretreatment 68Ga-PSMA PET images might be able to identify patients with an improved outcome and serve as a supportive tool in clinical decision making.

Multidisciplinary Postoperative Validation of 18F-FDG PET/CT Scan in Nodal Staging of Resected Non-Small Cell Lung Cancer.

BACKGROUND: The aim of this study was to examine the validity of PET/CT scans in the preoperative identification of lymph node metastases (LNM) and compare them with postoperative outcomes. METHODS: In this retrospective study, we included 87 patients with a solitary lung nodule or biopsy-proven non-small cell lung cancer treated in our institution from 2009 to 2015. Patients were divided into two groups and four subgroups, depending on pre- and postoperative findings. RESULTS: According to our analysis, PET/CT scan has a sensitivity of 50%, a specificity of 88.89%, a positive predictive value of 63.16%, and a negative predictive value of 82.35%. Among the patients, 13.8% were downstaged in PET-CT, while 8% were upstaged. In 78.2% of cases, the PET/CT evaluation was consistent with the histology. Metastases without extracapsular invasion were seldom recognized on PET/CT. CONCLUSIONS: This analysis showed the significance of extracapsular tumor invasion, which causes an inflammatory reaction, on LNM, which is probably responsible for preoperative false-positive findings. In conclusion, PET/CT scans are very effective in identifying patients without tumors. Furthermore, it is highly probable that patients with negative findings are free of disease.

Comparison of 18 F-NaF Imaging, 99m Tc-MDP Scintigraphy, and 18 F-FDG for Detecting Bone Metastases.

Bone is a common metastasis site in several malignancies, most importantly prostate and breast cancers. Given the significance of the early and accurate diagnosis of bone metastases for preliminary staging, treatment planning and monitoring, restaging, and survival prediction in patients with malignancy, it is critical to compare and contrast the strengths and weaknesses of imaging modalities. Although technetium-99m-labeled diphosphonates [ 99m Tc-MDP] scintigraphy has been used for assessing skeletal involvement, there is a renewed interest in fluorine-18-labeled sodium fluoride [ 18 F-NaF] bone imaging with positron emission tomography or positron emission tomography/computed tomography, since this approach provides essential advantages in bone metastases evaluation. This review study aimed to discuss the basic and technical aspects of 18 F-NaF imaging and its mechanism of action, and compare this modality with the 99m Tc-MDP bone scan and 18F-fluorodeoxyglucose using current evidence from the pertinent literature and case examples of the center in the study.

Diagnostic Value of Radiolabelled Somatostatin Analogues for Neuroendocrine Tumour Diagnosis: The Benefits and Drawbacks of [64Cu]Cu-DOTA-TOC.

Neuroendocrine tumours (NETs) arise from secondary epithelial cell lines in the gastrointestinal or respiratory system organs. The rate of development of these tumours varies from an indolent to an aggressive course, typically being initially asymptomatic. The identification of these tumours is difficult, particularly because the primary tumour is often small and undetectable by conventional anatomical imaging. Consequently, diagnosis of NETs is complicated and has been a significant challenge until recently. In the last 30 years, the advent of novel nuclear medicine diagnostic procedures has led to a substantial increase in NET detection. Great varieties of exclusive single photon emission computed tomography (SPECT) and positron emission tomography (PET) radiopharmaceuticals for detecting NETs are being applied successfully in clinical settings, including [111In]In-pentetreotide, [99mTc]Tc-HYNIC-TOC/TATE, [68Ga]Ga-DOTA-TATE, and [64Cu]Cu-DOTA-TOC/TATE. Among these tracers for functional imaging, PET radiopharmaceuticals are clearly and substantially superior to planar or SPECT imaging radiopharmaceuticals. The main advantages include higher resolution, better sensitivity and increased lesion-to-background uptake. An advantage of diagnosis with a radiopharmaceutical is the capacity of theranostics to provide concomitant diagnosis and treatment with particulate radionuclides, such as beta and alpha emitters including Lutetium-177 (177Lu) and Actinium-225 (225Ac). Due to these unique challenges involved with diagnosing NETs, various PET tracers have been developed. This review compares the clinical characteristics of radiolabelled somatostatin analogues for NET diagnosis, focusing on the most recently FDA-approved [64Cu]Cu-DOTA-TATE as a state-of-the art NET-PET/CT radiopharmaceutical.

A Review of Nuclear Medicine Approaches in the Diagnosis and the Treatment of Gynecological Malignancies.

Nuclear medicine is defined as the diagnosis and the treatment of disease using radiolabeled compounds known as radiopharmaceuticals. Single-photon emission computed tomography/computed tomography (SPECT/CT) and positron emission tomography/computer tomography (PET/CT) based radiopharmaceuticals have proven reliable in diagnostic imaging in nuclear medicine and cancer treatment. One of the most critical cancers that also relies on an early diagnosis is gynecological cancer. Given that approximately 25% of all cancers in developing countries are a subset of gynecological cancer, investigating this cancer subtype is of significant clinical worth, particularly in light of its high rate of mortality. With accurate identification of high grade distant abdominal endometrial cancer as well as extra abdominal metastases, 18F-Fluorodeoxyglucose ([18F]FDG) PET/CT imaging is considered a valuable step forward in the investigation of gynecological cancer. Considering these factors, [18F]FDG PET/CT imaging can assist in making management of patient therapy more feasible. In this literature review, we will provide a short overview of the role of nuclear medicine in the diagnosis of obstetric and gynecological cancers.

Radioembolization, Principles and indications.

Radioembolization is the selective application of radionuclide-loaded microspheres into liver arteries for the therapy of liver tumours and metastases. In this review, we focused on therapy planning and dosimetry, as well as the main indications of 90Y-glass and resin microspheres and 166Ho-microspheres.

99m Technetium-HMPAO-labeled platelet scan in practice: Preparation, quality control, and biodistribution studies

Abstract There is no biodistribution or imaging data on 99mtechnetium (Tc)-hexamethyl propylamine oxime (HMPAO)-labeled platelets in the literature. The current study aimed to present updated information about the clinical procedures for preparation and use of labeled platelets. Following two-step centrifugation at 1500 and 2500 rpm, the platelets were extracted from whole blood into platelet-rich plasma (PRP) above the buffy coat and then from PRP into a platelet pellet at the bottom of the tube. The 99mTc-HMPAO-labeled platelets were inspected for purity, viability, release of 99mTc from platelets, and sterility. Also, microscopic examination and thin layer chromatography (TLC) were performed. Biodistribution was assessed following necropsy in BALB/c mice and through imaging of New Zealand rabbits. The separation ratio was estimated at 98%, and radiochemical purity was measured to be 80%. The labeling efficiency was above 30% in more than half of the assays (range: 17-43%). The release of 99mTc from platelets was 9% per hour at 37ºC. After 24 hours, stability was estimated at 54% in the human serum. The target organs of mice included the spleen and liver. In rabbits, the imaging results indicated liver as the target organ. Thyroid uptake was negligible up to 90 minutes. Based on the findings, extraction of platelets and labeling them with 99mTc-HMPAO is a feasible and safe approach in routine practice.

Combination Therapies with PRRT.

Peptide receptor radionuclide therapy (PRRT) is a successful targeted radionuclide therapy in neuroendocrine tumors (NETs). However, complete responses remain elusive. Combined treatments anticipate synergistic effects and thus better responses by combining ionizing radiation with other anti-tumor treatments. Furthermore, multimodal therapies often have a balanced toxicity profile. To date, few studies have evaluated the effect of combination therapies with PRRT, some of them phase I/II trials. This review will focus on several clinically tested, tailored approaches to improving the effects of PRRT. The aim is to help clinicians in the treatment planning of NETs to choose the most effective and safe treatment for each patient in the sense of personalized medicine. Current promising combination partners of PRRT are somatostatin analogues (SSAs), chemotherapy, molecular targeted treatment, liver radioembolization, and dual radionuclide PRRT (Lutetium-177-PRRT combined with Yttrium-90-PRRT).

Feasibility and Therapeutic Potential of 177Lu-Fibroblast Activation Protein Inhibitor-46 for Patients With Relapsed or Refractory Cancers: A Preliminary Study.

INTRODUCTION: Fibroblast activation protein (FAP) is a member of the serine protease family and has a high expression in the stroma of approximately 90% of epithelial malignancies. The present investigation aimed to assess the feasibility, safety, and dosimetry data of 177Lu-FAPI-46 in diverse malignancies. PATIENTS AND METHODS: Patients with advanced cancers with nonoperable tumors, or tumors refractory to conventional therapies, were enrolled. Treatment included escalating doses of 177Lu-FAPI-46 (1.85-4.44 GBq) per cycle using a combination of clinical and statistical expertise design, and intervals of 4 to 6 weeks were considered between the cycles. Biodistribution and dosimetry were examined by whole-body scans. We applied the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 to measure peptide-targeted radionuclide therapy (PTRT)-associated toxicity. RESULTS: A total of 21 patients (11 females and 10 males) with a median age of 50 years (range, 6-79 years) were investigated. Of 21 participants, 18 cases were selected for PTRT. Overall, 36 PTRT cycles were performed. The median number of PTRT cycles and the median injected amount of activity in each cycle were 2 and 3.7 GBq, respectively. The dosimetric analysis revealed median absorbed doses of 0.026, 0.136, 0.886, and 0.02 with ranges of 0.023-0.034, 0.001-0.2, 0.076-1.39, and 0.002-0.2 mGy/MBq for the whole body, liver, kidneys, and spleen, respectively. The therapy was well tolerated in almost all patients. CONCLUSIONS: The findings of this preliminary investigation might indicate the potential feasibility and safety of PTRT using 177Lu-FAPI-46 for different aggressive tumors. Moreover, the current study could be beneficial in determining the suitable amount of activity for a phase 2 study.