Preclinical Evaluation of Biodistribution and Toxicity of [211At]PSMA-5 in Mice and Primates for the Targeted Alpha Therapy against Prostate Cancer.

Astatine (211At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the 211At-labeled prostate-specific membrane antigen (PSMA) compound ([211At]PSMA-5) exhibited excellent tumor growth suppression in a xenograft model. We conducted preclinical biodistribution and toxicity studies for the first-in-human clinical trial. [211At]PSMA-5 was administered to both normal male ICR mice (n = 85) and cynomolgus monkeys (n = 2). The mice were divided into four groups for the toxicity study: 5 MBq/kg, 12 MBq/kg, 35 MBq/kg, and vehicle control, with follow-ups at 1 day (n = 10 per group) and 14 days (n = 5 per group). Monkeys were observed 24 h post-administration of [211At]PSMA-5 (9 MBq/kg). Blood tests and histopathological examinations were performed at the end of the observation period. Blood tests in mice indicated no significant myelosuppression or renal dysfunction. However, the monkeys displayed mild leukopenia 24 h post-administration. Despite the high accumulation in the kidneys and thyroid, histological analysis revealed no abnormalities. On day 1, dose-dependent single-cell necrosis/apoptosis was observed in the salivary glands of mice and intestinal tracts of both mice and monkeys. Additionally, tingible body macrophages in the spleen and lymph nodes indicated phagocytosis of apoptotic B lymphocytes. Cortical lymphopenia (2/10) in the thymus and a decrease in the bone marrow cells (9/10) were observed in the 35 MBq/kg group in mice. These changes were transient, with no irreversible toxicity observed in mice 14 days post-administration. This study identified no severe toxicities associated with [211At]PSMA-5, highlighting its potential as a next-generation targeted alpha therapy for prostate cancer. The sustainable production of 211At using a cyclotron supports its applicability for clinical use.

Comparison of Nuclear Medicine Therapeutics Targeting PSMA among Alpha-Emitting Nuclides.

Currently, targeted alpha therapy (TAT) is a new therapy involving the administration of a therapeutic drug that combines a substance of α-emitting nuclides that kill cancer cells and a drug that selectively accumulates in cancer cells. It is known to be effective against cancers that are difficult to treat with existing methods, such as cancer cells that are widely spread throughout the whole body, and there are high expectations for its early clinical implementation. The nuclides for TAT, including 149Tb, 211At, 212/213Bi, 212Pb (for 212Bi), 223Ra, 225Ac, 226/227Th, and 230U, are known. However, some nuclides encounter problems with labeling methods and lack sufficient preclinical and clinical data. We labeled the compounds targeting prostate specific membrane antigen (PSMA) with 211At and 225Ac. PSMA is a molecule that has attracted attention as a theranostic target for prostate cancer, and several targeted radioligands have already shown therapeutic effects in patients. The results showed that 211At, which has a much shorter half-life, is no less cytotoxic than 225Ac. In 211At labeling, our group has also developed an original method (Shirakami Reaction). We have succeeded in obtaining a highly purified labeled product in a short timeframe using this method.

FAPI PET: Fibroblast Activation Protein Inhibitor Use in Oncologic and Nononcologic Disease.

Gallium 68 (68Ga)-labeled fibroblast activation protein (FAP) inhibitor (FAPI) PET is based on the molecular targeting of the FAP, which is known to be highly expressed in the major cell population in tumor stroma, termed cancer-associated fibroblasts. Among many FAP-targeted radiopharmaceuticals developed so far, 68Ga-FAPI exhibits rapid tracer accumulation in target lesions and low background signal, which results in excellent imaging features. FAPI PET can be integrated in the clinical workflow and enables the detection of small primary or metastatic lesions, especially in the brain, liver, pancreas, and gastrointestinal tract due to the low tracer accumulation in these organs. Moreover, the DOTA (1,4,7,10-tetraazacylclododecane-1,4,7,10-tetrayl tetraacetic acid) chelator in the molecular structure allows coupling of the FAPI molecules with therapeutic emitters such as yttrium 90 for theranostic applications. This review provides an overview of the state of the art in FAP imaging, summarizes the current knowledge of relevant cancer biology, and highlights the latest findings in the clinical use of 68Ga-FAPI PET and other current FAPI tracers. Published under a CC BY 4.0 license.

Targeted α-therapy using astatine (211At)-labeled PSMA1, 5, and 6: a preclinical evaluation as a novel compound.

PURPOSE: Targeted α-therapy (TAT) for prostate-specific membrane antigen (PSMA) is a promising treatment for metastatic castration-resistant prostate cancer (CRPC). Astatine is an α-emitter (half-life=7.2 h) that can be produced by a 30-MeV cyclotron. This study evaluated the treatment effect of 211At-labeled PSMA compounds in mouse xenograft models. METHODS: Tumor xenograft models were established by subcutaneous transplantation of human prostate cancer cells (LNCaP) in NOD/SCID mouse. [211At]PSMA1, [211At]PSMA5, or [211At]PSMA6 was administered to LNCaP xenograft mice to evaluate biodistribution at 3 and 24 h. The treatment effect was evaluated by administering [211At]PSMA1 (0.40 ± 0.07 MBq), [211At]PSMA5 (0.39 ± 0.03 MBq), or saline. Histopathological evaluation was performed for the at-risk organs at 3 and 6 weeks after administration. RESULTS: [211At]PSMA5 resulted in higher tumor retention compared to [211At]PSMA1 and [211At]PSMA6 (30.6 ± 17.8, 12.4 ± 4.8, and 19.1 ± 4.5 %ID/g at 3 h versus 40.7 ± 2.6, 8.7 ± 3.5, and 18.1 ± 2.2%ID/g at 24 h, respectively), whereas kidney excretion was superior in [211At]PSMA1 compared to [211At]PSMA5 and [211At]PSMA6. An excellent treatment effect on tumor growth was observed after [211At]PSMA5 administration. [211At]PSMA1 also showed a substantial treatment effect; however, the tumor size was relatively larger compared to that with [211At]PSMA5. In the histopathological evaluation, regenerated tubules were detected in the kidneys at 3 and 6 weeks after the administration of [211At]PSMA5. CONCLUSION: TAT using [211At]PSMA5 resulted in excellent tumor growth suppression with minimal side effects in the normal organs. [211At]PSMA5 should be considered a new possible TAT for metastatic CRPC, and translational prospective trials are warranted.

Evaluation of Astatine-211-Labeled Fibroblast Activation Protein Inhibitor (FAPI): Comparison of Different Linkers with Polyethylene Glycol and Piperazine.

Fibroblast activation proteins (FAP) are overexpressed in the tumor stroma and have received attention as target molecules for radionuclide therapy. The FAP inhibitor (FAPI) is used as a probe to deliver nuclides to cancer tissues. In this study, we designed and synthesized four novel 211At-FAPI(s) possessing polyethylene glycol (PEG) linkers between the FAP-targeting and 211At-attaching moieties. 211At-FAPI(s) and piperazine (PIP) linker FAPI exhibited distinct FAP selectivity and uptake in FAPII-overexpressing HEK293 cells and the lung cancer cell line A549. The complexity of the PEG linker did not significantly affect selectivity. The efficiencies of both linkers were almost the same. Comparing the two nuclides, 211At was superior to 131I in tumor accumulation. In the mouse model, the antitumor effects of the PEG and PIP linkers were almost the same. Most of the currently synthesized FAPI(s) contain PIP linkers; however, in our study, we found that PEG linkers exhibit equivalent performance. If the PIP linker is inconvenient, a PEG linker is expected to be an alternative.

Head-to-head intra-individual comparison of biodistribution and tumor uptake of 68Ga-FAPI and 18F-FDG PET/CT in cancer patients.

PURPOSE: FAPI ligands (fibroblast activation protein inhibitor), a novel class of radiotracers for PET/CT imaging, demonstrated in previous studies rapid and high tumor uptake. The purpose of this study is the head-to-head intra-individual comparison of 68Ga-FAPI versus standard-of-care 18F-FDG in PET/CT in organ biodistribution and tumor uptake in patients with various cancers. MATERIAL AND METHODS: This international retrospective multicenter analysis included PET/CT data from 71 patients from 6 centers who underwent both 68Ga-FAPI and 18F-FDG PET/CT within a median time interval of 10 days (range 1-89 days). Volumes of interest (VOIs) were manually drawn in normal organs and tumor lesions to quantify tracer uptake by SUVmax and SUVmean. Furthermore, tumor-to-background ratios (TBR) were generated (SUVmax tumor/ SUVmax organ). RESULTS: A total of 71 patients were studied of, which 28 were female and 43 male (median age 60). In 41 of 71 patients, the primary tumor was present. Forty-three of 71 patients exhibited 162 metastatic lesions. 68Ga-FAPI uptake in primary tumors and metastases was comparable to 18F-FDG in most cases. The SUVmax was significantly lower for 68Ga-FAPI than 18F-FDG in background tissues such as the brain, oral mucosa, myocardium, blood pool, liver, pancreas, and colon. Thus, 68Ga-FAPI TBRs were significantly higher than 18F-FDG TBRs in some sites, including liver and bone metastases. CONCLUSION: Quantitative tumor uptake is comparable between 68Ga-FAPI and 18F-FDG, but lower background uptake in most normal organs results in equal or higher TBRs for 68Ga-FAPI. Thus, 68Ga-FAPI PET/CT may yield improved diagnostic information in various cancers and especially in tumor locations with high physiological 18F-FDG uptake.

Sorbitol as a Polar Pharmacological Modifier to Enhance the Hydrophilicity of 99mTc-Tricarbonyl-Based Radiopharmaceuticals.

The organometallic technetium-99m tricarbonyl core, [99mTc][Tc(CO)3(H2O)3]+, is a versatile precursor for the development of radiotracers for single photon emission computed tomography (SPECT). A drawback of the 99mTc-tricarbonyl core is its lipophilicity, which can influence the pharmacokinetic properties of the SPECT imaging probe. Addition of polar pharmacological modifiers to 99mTc-tricarbonyl conjugates holds the promise to counteract this effect and provide tumor-targeting radiopharmaceuticals with improved hydrophilicities, e.g., resulting in a favorable fast renal excretion in vivo. We applied the "Click-to-Chelate" strategy for the assembly of a novel 99mTc-tricarbonyl labeled conjugate made of the tumor-targeting, modified bombesin binding sequence [Nle14]BBN(7-14) and the carbohydrate sorbitol as a polar modifier. The 99mTc-radiopeptide was evaluated in vitro with PC-3 cells and in Fox-1nu mice bearing PC-3 xenografts including a direct comparison with a reference conjugate lacking the sorbitol moiety. The glycated 99mTc-tricarbonyl peptide conjugate exhibited an increased hydrophilicity as well as a retained affinity toward the Gastrin releasing peptide receptor and cell internalization properties. However, there was no significant difference in vivo in terms of pharmacokinetic properties. In particular, the rate and route of excretion was unaltered in comparison to the more lipophilic reference compound. This could be attributed to the intrinsic properties of the peptide and/or its metabolites. We report a novel glycated (sorbitol-containing) alkyne substrate for the "Click-to-Chelate" methodology, which is potentially of general applicability for the development of 99mTc-tricarbonyl based radiotracers displaying an enhanced hydrophilicity.

Manganese in PET imaging: Opportunities and challenges.

Several radionuclides of the transition metal manganese are known and accessible. Three of them, 51 Mn, 52m Mn, and 52g Mn, are positron emitters that are potentially interesting for positron emission tomography (PET) applications and, thus, have caught the interest of the radiochemical/radiopharmaceutical and nuclear medicine communities. This mini-review provides an overview of the production routes and physical properties of these radionuclides. For medical imaging, the focus is on the longer-living 52g Mn and its application for the radiolabelling of molecules and other entities exhibiting long biological half-lives, the imaging of manganese-dependent biological processes, and the development of bimodal PET/magnetic resonance imaging (MRI) probes in combination with paramagnetic nat Mn as a contrast agent.

Simultaneous whole-body 18F-PSMA-1007-PET/MRI with integrated high-resolution multiparametric imaging of the prostatic fossa for comprehensive oncological staging of patients with prostate cancer: a pilot study.

INTRODUCTION: The aim of the present study was to explore the clinical feasibility and reproducibility of a comprehensive whole-body 18F-PSMA-1007-PET/MRI protocol for imaging prostate cancer (PC) patients. METHODS: Eight patients with high-risk biopsy-proven PC underwent a whole-body PET/MRI (3 h p.i.) including a multi-parametric prostate MRI after 18F-PSMA-1007-PET/CT (1 h p.i.) which served as reference. Seven patients presented with non-treated PC, whereas one patient presented with biochemical recurrence. SUVmean-quantification was performed using a 3D-isocontour volume-of-interest. Imaging data was consulted for TNM-staging and compared with histopathology. PC was confirmed in 4/7 patients additionally by histopathology after surgery. PET-artifacts, co-registration of pelvic PET/MRI and MRI-data were assessed (PI-RADS 2.0). RESULTS: The examinations were well accepted by patients and comprised 1 h. SUVmean-values between PET/CT (1 h p.i.) and PET/MRI (3 h p.i.) were significantly correlated (p < 0.0001, respectively) and similar to literature of 18F-PSMA-1007-PET/CT 1 h vs 3 h p.i. The dominant intraprostatic lesion could be detected in all seven patients in both PET and MRI. T2c, T3a, T3b and T4 features were detected complimentarily by PET and MRI in five patients. PET/MRI demonstrated moderate photopenic PET-artifacts surrounding liver and kidneys representing high-contrast areas, no PET-artifacts were observed for PET/CT. Simultaneous PET-readout during prostate MRI achieved optimal co-registration results. CONCLUSIONS: The presented 18F-PSMA-1007-PET/MRI protocol combines efficient whole-body assessment with high-resolution co-registered PET/MRI of the prostatic fossa for comprehensive oncological staging of patients with PC.

The Theranostic Optimization of PSMA-GCK01 Does Not Compromise the Imaging Characteristics of [99mTc]Tc-PSMA-GCK01 Compared to Dedicated Diagnostic [99mTc]Tc-EDDA/HYNIC-iPSMA in Prostate Cancer.

PURPOSE: Radiolabeled PSMA-ligands play a major role in today's nuclear medicine. Since approval of [177Lu]Lu-PSMA-617 for therapy of metastatic prostate cancer, availability of 177Lu became bottleneck of supply due to the high demand. Recently, a theranostic PSMA-ligand, PSMA-GCK01, was developed which can be labeled either diagnostically with 99mTc or therapeutically with 188Re with both nuclides available from well-known generator systems. This novel tracer might aid to overcome aforementioned supply limitations. In this investigation, the biodistribution and general imaging characteristics of [99mTc]Tc-PSMA-GCK01 were compared with the diagnostic reference compound [99mTc]Tc-EDDA/HYNIC-iPSMA in patients with advanced stage prostate cancer. In addition, the binding of both ligands to PSMA was analyzed at the molecular level using molecular docking. PROCEDURES: Two cohorts (n = 19 vs. n = 21) of patients with metastatic castration-resistant prostate cancer matched for age, tumor stage, and Gleason score underwent a planar gamma camera imaging with [99mTc]Tc-EDDA/HYNIC-iPSMA or [99mTc]Tc-PSMA-GCK01 prior to PSMA-ligand therapy for PSMA-phenotyping. The imaging data were retrospective analyzed for salivary gland, kidney, liver, soft tissue, and tumor uptake on a semi-automated ROI-analysis using HERMES Medical Solutions AB (HMS, Sweden). RESULTS: The data sets were semi-automated quantified on a ROI-based analysis. The tumor-to-background presented equal results of [99mTc]Tc-PSMA-GCK01 compared to [99mTc]Tc-EDDA/HYNIC-iPSMA. The physiological PSMA-positive organs like salivary gland presented also equal uptake in counts/MBq (salivary gland median 9.48 [99mTc]Tc-PSMA-GCK01 vs. median 9.11 [99mTc]Tc-EDDA/HYNIC-iPSMA), while liver-to-kidney ratio presented a slight shift to the liver parenchyma using [99mTc]Tc-PSMA-GCK01 (0.83) compared to [99mTc]Tc-EDDA/HYNIC-iPSMA (0.55) with no statistical significance. This is in agreement with the results from the docking study revealing only a minor difference in the docking scores for both ligands. CONCLUSIONS: The novel theranostic tracer [99mTc]Tc/[188Re]Re-PSMA-GCK01 demonstrates comparable general imaging characteristic with the reference compound [99mTc]Tc-EDDA/HYNIC-iPSMA. These results pave the way for the PSMA-targeting imaging and theranostic agents for a broader, rather low-cost, generator applied radio-ligand therapy utilization.

Radiomolecular Theranostics With Fibroblast-Activation-Protein Inhibitors and Peptides.

The advancement of theranostics, which combines therapeutic and diagnostic capabilities in oncology, has significantly impacted cancer management. This review explores fibroblast activation protein (FAP) expression in the tumor microenvironment (TME) and its association with various malignancies, highlighting its potential as a theranostic marker for PET/CT imaging using FAP-targeted tracers and for FAP-targeted radiopharmaceutical therapy. We examine the development and clinical applications of FAP inhibitors (FAPIs) and peptides, providing insights into their diagnostic accuracy, initial therapeutic efficacy, and clinical impact across diverse cancer types, as well as the synthesis of novel FAP-targeted ligands. This review aims to showcase the promising outcomes and challenges in integrating FAP-targeted approaches into cancer management.

PSMA-GCK01: A Generator-Based 99mTc/188Re Theranostic Ligand for the Prostate-Specific Membrane Antigen.

Prostate-specific membrane antigen (PSMA) theranostics have been introduced with 68Ga and 177Lu, the most used radionuclides. However, 188Re is a well-known generator-based therapeutic nuclide that completes a theranostic tandem with 99mTc and may offer an interesting alternative to the currently used radionuclides. In the present work, we aimed at the development of a PSMA-targeted 99mTc/188Re theranostic tandem. Methods: The ligand HYNIC-iPSMA was chosen as the lead structure. Its HYNIC chelator has limitations for 188Re labeling and was replaced by mercaptoacetyltriserine to obtain PSMA-GCK01, a precursor for stable 99mTc and 188Re labeling. 99mTc-PSMA-GCK01 was used for in vitro evaluation of the ligand and comparison with 99mTc-EDDA/HYNIC-iPSMA. Planar imaging using 99mTc-PSMA-GCK01 and organ biodistribution with 188Re-PSMA-GCK01 were performed using LNCaP tumor-bearing mice. Finally, the theranostic tandem was applied for imaging and therapy in 3 prostate cancer patients in compassionate care. Results: Efficient radiolabeling of PSMA-GCK01 with both radionuclides was demonstrated. Cell-based assays with 99mTc-PSMA-GCK01 versus 99mTc-EDDA/HYNIC-iPSMA revealed comparable uptake characteristics. Planar imaging and organ distribution revealed good tumor uptake of both 99mTc-PSMA-GCK01 and 188Re-PSMA-GCK01 at 1 and 3 h after injection, with low uptake in nontarget organs. In patients, similar distribution patterns were observed for 99mTc-PSMA-GCK01 and 188Re-PSMA-GCK01 and in comparison with 177Lu-PSMA-617. Conclusion: The ligand PSMA-GCK01 labels stably with 99mTc and 188Re, both generator-based radionuclides, and thus provides access to on-demand labeling at reasonable costs. Preclinical evaluation of the compounds revealed favorable characteristics of the PSMA-targeted theranostic tandem. This result was confirmed by successful translation into first-in-humans application.

Initial Evaluation of [18F]FAPI-74 PET for Various Histopathologically Confirmed Cancers and Benign Lesions.

The 18F-labeled fibroblast activation protein inhibitor (FAPI) [18F]FAPI-74 has the benefit of a higher synthetic yield and better image resolution than 68Ga-labeled FAPI. We preliminarily evaluated the diagnostic performance of [18F]FAPI-74 PET in patients with various histopathologically confirmed cancers or suspected malignancies. Methods: We enrolled 31 patients (17 men and 14 women) with lung cancer (n = 7), breast cancer (n = 5), gastric cancer (n = 5), pancreatic cancer (n = 3), other cancers (n = 5), and benign tumors (n = 6). Twenty-seven of the 31 patients were treatment-naïve or preoperative, whereas recurrence was suspected in the remaining 4 patients. Histopathologic confirmation was obtained for the primary lesions of 29 of the 31 patients. In the remaining 2 patients, the final diagnosis was based on the clinical course. [18F]FAPI-74 PET scanning was performed 60 min after the intravenous injection of [18F]FAPI-74 (240 ± 31 MBq). The [18F]FAPI-74 PET images were compared between the primary or local recurrent lesions of malignant tumors (n = 21) and nonmalignant lesions (n = 8: type-B1 thymomas, granuloma, solitary fibrous tumor, and postoperative or posttherapeutic changes). The uptake and number of detected lesions on [18F]FAPI-74 PET were also compared with those on [18F]FDG PET for available patients (n = 19). Results: [18F]FAPI-74 PET showed higher uptake in primary lesions of various cancers than in nonmalignant lesions (median SUVmax, 9.39 [range, 1.83-25.28] vs. 3.49 [range, 2.21-15.58]; P = 0.053), but some of the nonmalignant lesions showed high uptake. [18F]FAPI-74 PET also showed significantly higher uptake than [18F]FDG PET (median SUVmax, 9.44 [range, 2.50-25.28] vs. 5.45 [range, 1.22-15.06] in primary lesions [P = 0.010], 8.86 [range, 3.51-23.33] vs. 3.84 [range, 1.01-9.75] in lymph node metastases [P = 0.002], and 6.39 [range, 0.55-12.78] vs. 1.88 [range, 0.73-8.35] in other metastases [P = 0.046], respectively). In 6 patients, [18F]FAPI-74 PET detected more metastatic lesions than [18F]FDG PET. Conclusion: [18F]FAPI-74 PET showed higher uptake and detection rates in primary and metastatic lesions than did [18F]FDG PET. [18F]FAPI-74 PET is a promising novel diagnostic modality for various tumors, especially for precise staging before treatment, including characterization of tumor lesions before surgery. Moreover, 18F-labeled FAPI ligand might serve a higher demand in clinical care in the future.

Evaluation of a Radiolabeled Macrocyclic Peptide as Potential PET Imaging Probe for PD-L1.

The interaction between the immune checkpoint PD-1 and PD-L1 promotes T-cell deactivation and cancer proliferation. Therefore, immune checkpoint inhibition therapy, which relies on prior assessment of the target, has been widely used for many cancers. As a non-invasive molecular imaging tool, radiotracers bring novel information on the in vivo expression of biomarkers (e. g., PD-L1), enabling a personalized treatment of patients. Our work aimed at the development of a PD-L1-specific, peptide-based PET radiotracer. We synthesized and evaluated a radiolabeled macrocyclic peptide adapted from a patent by Bristol Myers Squibb. Synthesis of [68 Ga]Ga-NJMP1 yielded a product with a radiochemical purity>95 % that was evaluated in vitro. However, experiments on CHO-K1 hPD-L1 cells showed very low cell binding and internalization rates of [68 Ga]Ga-NJMP1 in comparison to a control radiopeptide (WL12). Non-radioactive cellular assays using time-resolved fluorescence energy transfer confirmed the low affinity of the reported parent peptide and the DOTA-derivatives towards PD-L1. The results of our studies indicate that the macrocyclic peptide scaffold reported in the patent literature is not suitable for radiotracer development due to insufficient affinity towards PD-L1 and that C-terminal modifications of the macrocyclic peptide interfere with important ligand/receptor interactions.

Unexpected transformation of n.c.a. [111In]InCl3 in stock solutions into an unreactive [111In]In-species.

While performing multiple indium-111 labeling of DOTA-modified peptides from a single batch of [111In]InCl3, inconsistent radiochemical yields were observed. We found that the formation of a radioactive impurity in the [111In]InCl3 stock solution hampered the reactivity of the indium-111 during radiolabeling reactions. The formation of this unknown 111In-species could be successfully suppressed by increasing the concentration of chloride ions in the stock solution and [111In]InCl3 was "recovered". Radiolabeling of DOTA-peptides with the stabilized [111In]InCl3 resulted again in acceptable radiochemical yields. In addition, we report convenient iTLC systems that allow distinguishing between [111In]InCl3, the formed unknown 111In-species, radiocolloids, and radiolabeled peptides (DOTANOC).

Advancement and Future Perspective of FAPI PET/CT In Gynecological Malignancies.

Fibroblast activation protein (FAP) is ubiquitously present in healthy tissue, and additionally upregulated by cancer associated fibroblasts (CAFs) leading to high levels of FAP. Thus, neoplastic tissue, which is containing CAFs, characterized by a high presence of FAP. Moreover, in more than 90% of all epithelial tumors this phenomenon seems to occur, including many gynecological tumors, providing the foundation for a successful application of FAP-ligands. However, FAP upregulation, can also be initiated by benign conditions such as inflammation, hormonal-influence, and wound healing. Gynecological cancers seem to represent a field of interest for the utilization of FAPI-PET/CT to potentially improve staging, restaging and therapeutic management. First highly promising investigations demand further research in order to validate these preliminary findings.

Positive Multifocal PSMA PET/CT in a Patient With Prostate Cancer and Follicular Lymphoma.

ABSTRACT: Prostate-specific membrane antigen (PSMA) PET/CT is a highly reliable nuclear tracer for diagnostic imaging of prostate cancer. However, PSMA is also expressed by some nonprostatic tissues such as benign tumors, inflammatory processes, and malignant neoplasms. This case presents a patient with prostate cancer and follicular lymphoma undergoing PSMA PET/CT. Remarkably, both tumor entities were clearly detected in the scan. Yet, the 2 malignancies demonstrated rather different ranges in terms of SUVmax uptake values and therefore still enabled precise and accurate discrimination of prostate cancer and follicular lymphoma.

The 5-HT1A receptor antagonist WAY-100635 decreases motor/exploratory behaviors and nigrostriatal and mesolimbocortical dopamine D2/3 receptor binding in adult rats.

Serotonin(5-HT)ergic projections run from the raphe nuclei to dopamin(DA)ergic cells in substantia nigra/ventral tegmental area (SN/VTA) and to the terminal fields of DA neurons in nucleus accumbens, caudateputamen and neocortex. In the present studies, we assessed the effect of the 5-HT1A receptor (R) antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarbox-amide maleate (WAY-100635) on motor and exploratory behaviors and on D2/3R binding in the rat brain with in vivo imaging methods. D2/3R binding was determined in the same animals after systemic application of WAY-100635 (0.4 mg/kg) and 0.9% saline (SAL), respectively, with [123I]IBZM as SPECT ligand. Anatomical information for the delineation of the target regions was obtained with dedicated small animal MRI. Immediately after treatment with WAY-100635 or SAL, motor/exploratory behaviors were assessed for 30 min in two different batches of animals in an open field. WAY-100635 reduced D2/3R binding in caudateputamen, thalamus, frontal cortex, parietal cortex and ventral hippocampus relative to SAL. Network analysis of regional binding data after WAY-100635 yielded positive connections between (1) caudateputamen and substantia nigra/ventral tegmental area, (2) caudateputamen and ventral hippocampus, (3) substantia nigra/ventral tegmental area and parietal cortex, (4) thalamus and dorsal hippocampus and (5) frontal cortex and parietal cortex, which were not present after SAL. Moreover, WAY-100635 decreased parameters of motor activity (overall activity, ambulation duration and frequency) but increased the duration of grooming behavior relative to SAL. The effect on exploration was time-dependent with an early increase and a subsequent decrease of behavioral parameters (rearing duration and frequency, frequency of head-shoulder motility). For WAY-100635, findings imply a region-specificity as well as a time-dependency of DAergic action.