Enhancing PSMA-uptake with androgen deprivation therapy - a new way to detect prostate cancer metastases?

PURPOSE: 68Ga-PSMA PET/CT imaging is a promising modality for the staging of recurrent prostate cancer (PCa). Current evidence suggests limited diagnostic value of the 68Ga-PSMA PET/CT in PSA-levels ≤0.3ng/mL. Experimental data have demonstrated na increase in PSMA-expression in PCa metastases by androgen deprivation in vitro. The aim of the current study was to investigate a possible enhancing effect of PSMA with low-dose androgen deprivation in patients with BCR and low PSA-levels. MATERIALS AND METHODS: Five patients with PCa and BCR, following radical prostatectomy, underwent 68Ga-PSMA PET/CT. A consecutive 68Ga-PSMA PET/CT was performed 6 to 11 days after injection of 80mg of Degarelix (Firmagon®). We recorded PSA and testosterone serum-levels and changes of PSMA-uptake in 68Ga-PSMA PET/CT images. RESULTS: Median PSA prior 68Ga-PSMA PET/CT was 0.27ng/mL. All patients had a decrease in testosterone serum levels from median 2.95µg/l to 0.16µg/l following Degarelix injection. We observed an increase in the standardized uptake value (SUV) in PSMA-positive lymphogenous and osseous lesions in two patients following androgen deprivation. In another two patients, no PSMA positive signals were detected in either the fi rst or the second scan. CONCLUSION: Our preliminary results of this feasibility assessment indicate a possible enhancing effect of PSMA-imaging induced by low-dose ADT. Despite several limitations and the small number of patients, this could be a new approach to improve staging by 68Ga-PSMA PET/CT in PCa patients with BCR after primary therapy. Further prospective studies with larger number of patients are needed to validate our findings.

[Incidence and Predictive Factors for Bilaterality in Patients with Papillary Thyroid Carcinoma]. / Inzidenz und prädiktive Faktoren des bilateralen papillären Schilddrüsenkarzinoms.

BACKGROUND: The optimal extent of thyroidectomy for papillary thyroid cancer (PTC) ≥ 10 mm und < 10 mm is still controversial. Therefore, the purpose of this study was to investigate factors predictive for bilaterality in patients with papillary thyroid carcinoma (PTC). MATERIAL AND METHODS: We retrospectively reviewed 123 PTC patients in a single centre study who underwent either completion or total thyroidectomy and analysed the predictive value of tumour size, histological parameters, multifocality, and lymph node metastases with primary tumour size of ≥ 10 mm and < 10 mm as well as for ≥ 7 mm and < 7 mm. RESULTS: Out of 123 patients, 26 exhibited bilateral PTC. This was significantly more frequent in patients with a primary tumour size of ≥ 10 mm (77%) compared to a tumour size of < 10 mm (23%) (p = 0.004). Multifocality was found to be an independent predictive factor for bilaterality (p = 5.022e-18). Metachronous lymph node metastases showed a trend for bilateral PTCs (p = 0.0691). These findings were reproducible for the comparison between the ≥ 7 mm and < 7 mm group. CONCLUSION: The presence of bilateral PTC appears to be related to the size of the primary tumour ≥ 10 mm. Multifocality is a positive predictor for bilaterality. When multifocality, even with a primary tumour size of < 10 mm, is observed in patients with PTC, total thyroidectomy or completion thyroidectomy may be considered. If lobectomy is performed in patients with PTC, meticulous follow-up is needed to detect hidden malignancies in the contralateral lobe.

See the unseen: Mesorectal lymph node metastases in prostate cancer.

BACKGROUND: Our study is the first evaluation of nodal metastatic prostate cancer (PCa) to mesorectal lymph nodes (MLN) detected by (68) Ga-PSMA-PET/CT. METHODS: We retrospectively analyzed 76 consecutive PCa patients who underwent (68) Ga-PSMA-PET/CT: 61 PCa patients with biochemical recurrence (BCR) after curative treatment and 15 high-risk PCa before primary therapy. We assessed PET-positive MLN, which are indicative for PCa. RESULTS: We detected PET-positive lesions for PCa in (68) Ga-PSMA-PET/CT in 66 of 76 (87%) patients. Nodal disease was imaged in 47 of 66 (71%) patients. Indicative mesorectal nodal lesions for PCa were detected in 12 of 76 (15.8%) patients. The median number of PET-positive MLN was one per patient. Seven of twelve patients had recurrent PCa after radical prostatectomy with a median PSA value of 1.84 ng/ml (range 0.31-13). Five of twelve patients had untreated first diagnosed high-risk PCa with median PSA value of 90 ng/ml (range 4.6-93) at PET/CT, respectively. For all PET positive MLN a morphological correlate was found in CT (shortest diameter median 4 mm [range 4-21]; longest diameter median 7.5 mm [range 5-25]). After PET/CT, four patients with recurrent PCa received hormonal therapy, one patient was treated with directed radiation therapy of MLN, one patient received chemotherapy, and one patient was treated with pelvic lymph node dissection. Three high-risk PCa patients received hormonal therapy, and two patients were treated with adjuvant hormonal therapy after radical prostatectomy. CONCLUSIONS: Detection and exact location of nodal metastasis for PCa is crucial for the choice of treatment and the patient's prognosis. (68) Ga-PSMA-PET/CT seems to improve the detection of nodal metastasis in PCa, especially concerning mesorectal lymph nodes.

Biphasic 68Ga-PSMA-HBED-CC-PET/CT in patients with recurrent and high-risk prostate carcinoma.

PURPOSE: Binding of (68)Ga-PSMA-HBED-CC ((68)Ga-PSMA) at prostate cancer (PC) cells increases over time. A biphasic protocol may help separating benign from tumor lesions. The aim of this study was the retrospective evaluation of a diagnostic incremental value of a dual-time point (biphasic) (68)Ga-PSMA-PET/CT in patients with prostate cancer. METHODS: Retrospective analysis of 35 consecutive patients (49-78 years, median 71) with newly diagnosed PC (12/35) or recurrence of PC (23/35). PET/CT (Gemini TF16, Philips) was acquired 1 h and 3 h p. i. of 140-392 MBq (300 MBq median) (68)Ga-PSMA, followed by a diagnostic contrast CT. PET findings were correlated with histology or unequivocal CT findings. Semiquantitative PET data (SUVmax, SUV mean) were acquired and target-to-background-ratios (T/B-ratio) were calculated for benign and malign lesions for both time points. Size of lymph nodes (LN) on diagnostic CT was recorded. Statistical analysis was performed for assessment of significant changes of semiquantitative PET-parameters over time and for correlation of size and uptake of lymph nodes. RESULTS: One hundred and four lesions were evaluated. Sixty lesions were referenced by histology or unequivocal CT findings, including eight (13.3 %) histopathologically benign lymph nodes, 12 (20 %) histopathologically lymph node metastases, 12 (20 %) primary tumors, three (5 %) local recurrences, and 25 (41.7 %) bone metastases. Forty-four lesions were axillary LN with normal CT-appearance. Benign lesions had significantly lower SUVmax and T/B-ratios compared with malignant findings. Malign lesions showed a significant increase of both parameters over time compared to benign findings. There was no correlation between LN size and SUVmax. The sensitivity, specificity, the positive predictive value and negative predictive value of PET/CT regarding pelvic LN was 94 %, 99 %, 89 %, and 99.5 %, respectively. CONCLUSIONS: In contrast to benign tissues, the uptake of proven tumor lesions increases on (68)Ga-PSMA-PET/CT over time. A biphasic PET-study may lead to a better detection of tumor lesions in unequivocal findings.

The impact of nodal tumour burden on lymphoscintigraphic imaging in patients with melanomas.

PURPOSE: To retrospectively study the influence of nodal tumour burden on lymphoscintigraphic imaging in 509 consecutive patients with melanomas. METHODS: Bidirectional lymphatic drainage, the clear depiction of an afferent lymphatic vessel, time to depiction of the first sentinel lymph node (SLN) and number of depicted and excised nodes were recorded. Nodal tumour load was classified as SLN-negative, SLN micrometastases or macrometastases. RESULTS: In the overall population, using multivariate regression analysis, a short SLN depiction time was significantly associated with the depiction of a greater number of radioactive nodes, a short distance between the primary tumour site and the nodal basin, younger age and lower nodal tumour burden. The proportion of patients with clear depiction of an afferent lymphatic vessel depended on the nodal tumour load (46% in SLN-negative patients, 57% in SLN positive patients, and 69% in patients with macrometastases; P = 0.009). Macrometastasis was significantly associated with delayed depiction of the first radioactive node and a greater number of depicted hotspots. In patients with clinically nonsuspicious nodes, i.e. the classical target group for SLN biopsy, clear depiction of an afferent vessel was significantly associated with a higher number of SLNs during dynamic acquisition, SLN micrometastasis and a higher overall number of metastatic lymph nodes after SLN biopsy plus completion lymphadenectomy. The excision of more than two SLNs did not increase the metastasis detection rate. In patients with bidirectional or tridirectional lymphatic drainage, the SLN positivity rates for the first, second and third basin were 25.4%, 11.7% and 0.0 %, respectively (P = 0.002). CONCLUSION: In patients with clinically nonsuspicious lymph nodes, clear depiction of an afferent lymph vessel may be a sign of micrometastasis. Macrometastasis is associated with prominent afferent vessels, delayed depiction of the first radioactive node and a higher number of depicted hotspots.

Individualized surgery: gamma-probe-guided lymphadenectomy in patients with clinically enlarged lymph node metastases from melanomas.

BACKGROUND: The value of a preoperative lymphoscintigraphy in melanoma patients with clinically evident regional lymph node metastases has not been studied. Therapeutic lymph node dissection (TLND) is regarded as the clinical standard, but the appropriate extent of TLND is controversial in all lymphatic basins. PATIENTS AND METHODS: Of the 115 consecutive patients with surgery on palpable lymph node metastases, 34 received a pre-operative lymphoscintigraphy. Lymphatic drainage to a second nodal basin outside the clinically involved basin was found in 15 cases. In 13 patients, the ectopic tumor-draining lymph nodes were excised as in a sentinel node biopsy. The lymph nodes from the TLND specimens were postoperatively separated and classified as either radioactive or non-radioactive. RESULTS: A total of 493 lymph nodes were examined pathologically. The largest macrometastasis maintained the ability to take up radiotracer in 77% of cases. Radioactively labeled lymph nodes carried a higher risk of being involved with metastasis. The proportions of tumor involvement for radioactive and non-radioactive lymph nodes were 44.5 and 16.9%, respectively (P=0.00002). Of the 13 ectopic nodal basins surgically explored, six harbored clinically occult metastases. CONCLUSION: In patients undergoing TLND for palpable metastases, tumor-draining lymph nodes in a second, ectopic nodal basin should be excised, because they could be affected by occult metastasis. With respect to radioactive lymph nodes situated within the nodal basin of the macrometastasis but beyond the borders of a less-radical lymphadenectomy, further studies are needed.

Brain 18 F-FDG-PET and an optimized cingulate island ratio to differentiate Lewy body dementia and Alzheimer's disease.

BACKGROUND AND PURPOSE: The diagnosis of Dementia with Lewy Bodies (DLB) is challenging due to various clinical presentations and clinical and neuropathological features that overlap with Alzheimer's disease (AD). The use of 18 F-Fluorodeoxyglucose-PET (18 F-FDG-PET) can be limited due to similar patterns in DLB and AD. However, metabolism in the posterior cingulate cortex is known to be relatively preserved in DLB and visual assessment of the "cingulate island sign" became a helpful tool in the analysis of 18F-FDG-PET. The aim of this study was the evaluation of visual and semiquantitative 18F-FDG-PET analyses in the diagnosis of DLB and the differentiation to AD as well as its relation to other dementia biomarkers. METHODS: This retrospective study comprises 81 patients with a clinical diagnosis of DLB or AD that underwent 18 F-FDG-PET/CT. PET scans were analyzed visually and semiquantitatively and results were compared to clinical data, cerebrospinal fluid results, dopamine transporter scintigraphy, and 18F-Florbetaben-PET. Furthermore, different cingulate island ratios were calculated to analyze their diagnostic accuracy. RESULTS: Visual assessment of 18F-FDG-PET showed an accuracy of 62%-77% in differentiating between DLB and AD. Standard uptake values were significantly lower in the primary visual cortex and the lateral occipital cortex of DLB patients compared to AD patients. The cingulate island ratio was significantly higher in the DLB group compared to the AD group and the ratio posterior cingulate cortex to visual cortex plus lateral occipital cortex showed the highest diagnostic accuracy to discriminate between DLB and AD at 81%. CONCLUSIONS: Semiquantitative 18F-FDG-PET imaging and especially the use of an optimized cingulate island ratio are valuable tools to differentiate between DLB and AD.

Blastomatoid pulmonary carcinosarcoma: report of a case with a review of the literature.

BACKGROUND: Pulmonary carcinosarcoma is a biphasic tumour with an unfavourable prognosis. The differential diagnosis includes pulmonary blastoma and is often challenging. CASE PRESENTATION: We here describe a case of blastomatoid pulmonary carcinosarcoma in a 58-year-old patient, who underwent surgical resection. Histopathological examination revealed immature glandular epithelium resembling high-grade fetal adenocarcinoma expressing epithelial markers and membranous beta-catenin, and blastomatoid spindle cells with partial rhabdomyosarcoma-like differentiation. Both elements expressed p53, MDM2, and cyclin-dependent kinase 4 (CDK4), but not thyroid-transcription factor 1 (TTF-1). Mutation analysis of KRAS, EGFR, and beta-catenin revealed no mutations. Comparative genomic hybridization detected +1q, +6p, +6q24qter, +8q, +11q12q14, +11q23qter, +12q12q21, +12q24qter, +17q, +20q, -5q14q23, -9p13pter, -13q21q21, and amplifications at 12q14q21, 15q24qter, 20q11q12. CONCLUSION: The observed molecular and cytogenetic findings may provide additional tools for the differential diagnosis of biphasic pulmonary neoplasms. Furthermore, TP53, MDM2, CDK4, and PTPN1 may be involved in tumourigenesis.

The Role of PSMA PET/CT in the Primary Diagnosis and Follow-Up of Prostate Cancer-A Practical Clinical Review.

The importance of PSMA PET/CT in both primary diagnostics and prostate cancer recurrence has grown steadily since its introduction more than a decade ago. Over the past years, a vast amount of data have been published on the diagnostic accuracy and the impact of PSMA PET/CT on patient management. Nevertheless, a large heterogeneity between studies has made reaching a consensus difficult; this review aims to provide a comprehensive clinical review of the available scientific literature, covering the currently known data on physiological and pathological PSMA expression, influencing factors, the differences and pitfalls of various tracers, as well as the clinical implications in initial TNM-staging and in the situation of biochemical recurrence. This review has the objective of providing a practical clinical overview of the advantages and disadvantages of the examination in various clinical situations and the body of knowledge available, as well as open questions still requiring further research.

Development of high-affinity fluorinated ligands for cannabinoid subtype 2 receptor, and in vitro evaluation of a radioactive tracer for imaging.

The development of neurodegenerative diseases is associated with cerebral inflammation, which activates resident immune cells of the central nervous system (CNS), namely microglial cells that show an up-regulation of the cannabinoid subtype 2 receptor (CB2R) expression. Therefore our work aimed to design and synthesize a radiotracer for the detection of CB2R expression by positron emission tomography (PET) allowing an early diagnosis of neurodegenerative diseases. For the development of such a PET tracer, N-alkyl-substituted indole-3-yl-tetramethylcyclopropylketones served as lead structures due to their high CB2R potency and selectivity, allowing radiolabeling on the N-alkyl chain. To this end, eight novel fluorinated N-alkyl-indole-3-yl-tetramethylcyclopropylketones were synthesized, investigated in radioligand binding studies, and structure-activity relationships were evaluated. The most promising candidate was (1-(4-fluoropropyl)-1H-indole-3-yl)(2,2,3,3-tetramethyl-cyclopropyl)methanone (Ki: 7.88 nM at the CB2R, 3430 nM at cannabinoid subtype 1 receptor (CB1R)). A precursor was synthesized, radiofluorinated with no-carrier-added [18F]F- by nucleophilic substitution of a tosyl group, and the resulting PET ligand was purified, all being performed on a fully automated synthesis module. The tracer was produced in 34 ± 6% radiochemical yield within 2 h and with molar activities of up to 1500 GBq/µmol. A first preclinical evaluation was carried out including determination of logP, metabolic stability by liver microsomes, and autoradiography. The novel PET tracer for imaging CB2R showed promising results warranting subsequent clinical evaluation.

Tandem high-dose therapy in relapsed and refractory B-cell lymphoma: results of a prospective phase II trial of myeloablative chemotherapy, followed by escalated radioimmunotherapy with (131)I-anti-CD20 antibody and stem cell rescue.

A phase II trial evaluated safety, feasibility and efficacy of a sequential tandem approach combining myeloablative BEAM chemotherapy and autologous stem cell transplantation (ASCT) with myeloablative radioimmunotherapy (HD-RIT), with (131)I-anti-CD20 antibody ((131)I-rituximab), followed by a second ASCT in patients with relapsed or refractory CD20+ B-cell lymphoma. According to protocol, 16 patients with relapsed (n = 14) and refractory (n = 2) CD20+ B-cell lymphoma received salvage therapy with rituximab and Dexa-BEAM, followed by BEAM (HD chemotherapy) and high-dose myeloablative radioimmunotherapy 2-6 months after BEAM. Nine of 16 patients received HD-RIT; seven patients were excluded before HD-RIT because of toxicity or progressive disease. Disease histologies were follicular lymphoma (FL) grades 1 and 2 (n = 4), transformed follicular (FL 3b; n = 6), diffuse large B-cell (DLBCL; n = 4), mantle cell (n = 1) and marginal zone lymphoma (n = 1). After a median follow-up of 50.4 months for OS and 39.7 months for progression-free survival (PFS), estimated 4-year OS and PFS were 67% and 64%, respectively. The estimated 4-year OS and PFS for patients with FL were 80% and 78%, respectively. Toxicity was significant, including one fatal outcome due to pneumonitis. Tandem transplants consisting of HD chemotherapy followed by HD-RIT with (131)I-coupled anti-CD20 are manageable and effective but toxic treatment modalities for relapsed poor prognosis CD20+ B-NHL.

The popliteal fossa - a problem zone for sentinel lymphonodectomy.

BACKGROUND: The impact of lymphatic drainage to popliteal sentinel lymph nodes (SLNs) has yet to be explored in detail. PATIENTS AND METHODS: We performed lymphoscintigraphy on 663 patients with cutaneous melanomas. The following day sentinel lymphonodectomy was performed. SLNs were studied on serial sections with both histology and immunohistochemistry. RESULTS: 166 patients had a melanoma located on the foot, the lower leg or the knee, i. e., the potential of lymphatic drainage to the popliteal lymph nodes. On lymphoscintigraphy, only 16 patients (9.6 %) showed popliteal SLNs. A popliteal SLN was surgically identified in only 6 of the 16 patients. The reason for the poor identification rate was exhausted radioactivity in the small popliteal nodes the day after lymphoscintigraphy. In 3 cases, popliteal SLN metastasis was diagnosed. All but one patient had an additional drainage to the inguinal lymph nodes; inguinal SLN metastasis was diagnosed in 7 patients. Even all 16 patients showed lymphatic drainage to iliac lymph nodes, metastasis in the pelvis was diagnosed in 4 patients. CONCLUSIONS: Popliteal SLNs are observed in less than 10 % of the patients with melanomas of the distal leg. In the case of suspected popliteal drainage, lymphoscintigraphy should be performed on the day of sentinel lymphonodectomy because the radioactivity of the small and deeply situated popliteal nodes diminishes rapidly. With respect to complete lymphadenectomy, decision-making is difficult since three nodal basins (popliteal, inguinal and iliac) may harbor metastases.

Mesorectal Lymph Node Metastases as Index Lesion in 68Ga-PSMA-PET/CT Imaging for Recurrent Prostate Cancer.

Purpose: Several studies have demonstrated an advantage of 68Ga-PSMA-PET/CT as staging modality for detection of prostate cancer (PCa) metastases. Data concerning metastatic manifestation and impact on PCa development of mesorectal lymph nodes (MLN) is limited. Our investigation describes MLN metastases as index lesion in 68Ga-PSMA PET/CT imaging for recurrent PCa. Methods: Twelve PCa patients with biochemical recurrence (BCR) after primary therapy who prospectively underwent a baseline 68Ga-PSMA-PET/CT initially showed MLN metastases. Eight of these patients received a follow-up 68Ga-PSMA-PET/CT to evaluate treatment response and further evolution. Prostate-specific antigen (PSA)-levels, changes in PSMA-uptake of MLN metastases and further 68Ga-PSMA PET/CT findings were recorded. Results: Median PSA at the first 68Ga-PSMA-PET/CT was 5.39 ng/ml. In all patients therapeutic management changed after the first 68Ga-PSMA-PET/CT. Androgen deprivation therapy (ADT) was initiated in seven of eight patients, one patient restarted initial ADT. Three patients additionally received salvage radiation therapy (sRT) including the prostatic lodge and docetaxel chemotherapy was started in one case. At follow-up, a decrease of PSA-level was detected in all patients (median 2.05 ng/ml) after median 10 months. In six of eight patients we observed a decrease or complete regress of PSMA-uptake in MLN in the follow-up 68Ga-PSMA-PET/CT. Conclusion: MLN metastases detected by 68Ga-PSMA-PET/CT seem to be a relevant localization of tumor manifestation and may serve as index lesion in the treatment of recurrent PCa. Besides the known oncological benefits of ADT and sRT, in case of sole MLN metastases individualized therapy like salvage lymphadenectomy or RT with a defined radiation field could be options for these patients.

Liver Enzyme Elevation After 177Lu-PSMA Radioligand Therapy for Metastasized Castration-Resistant Prostate Cancer.

177Lu-PSMA radioligand therapy is a promising new option for patients with metastasized castration-resistant prostate cancer, and the spectrum of adverse events with this treatment has to be evaluated. Here, we describe the case of a patient with M1c disease (metastasis to the mediastinum, lungs, bones, and liver) who presented with elevated liver enzyme levels after receiving 177Lu-PSMA radioligand therapy for castration-resistant prostate cancer. Pretreatment 68Ga-PSMA PET/CT showed at least 4 liver lesions with low uptake. Overall, the liver uptake was inhomogeneous. Liver biopsy was performed subsequently.

Impact of rs12917 MGMT Polymorphism on [18F]FDG-PET Response in Pediatric Hodgkin Lymphoma (PHL).

PURPOSE: The enzyme O6-methylguanine-DNA methyltransferase (MGMT) is an important component of the DNA repair machinery. MGMT removes O6-methylguanine from the DNA by transferring the methyl group to a cysteine residue in its active site. Recently, we detected the single nucleotide polymorphism (SNP) rs12917 (C/T) in the MGMT sequence adjacent to the active site in Hodgkin lymphoma (HL) cell line KM-H2. We now investigated whether this SNP is also present in other HL cell lines and patient samples. Furthermore, we asked whether this SNP might have an impact on metabolic response in 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography ([18F]FDG-PET), and on overall treatment outcome based on follow-up intervals of at least 34 months. PROCEDURES: We determined the frequency of this MGMT polymorphism in 5 HL cell lines and in 29 pediatric HL (PHL) patients. The patient cohort included 17 female and 12 male patients aged between 4 and 18 years. After characterization of the sequence, we tested a possible association between rs12917 and age, gender, Ann Arbor stage, treatment group, metabolic response following two courses of OEPA (vincristine, etoposide, prednisone, and doxorubicin) chemotherapy, radiotherapy indication, and relapse status. RESULTS: We detected the minor T allele in four of five HL cell lines. 11/29 patients carried the minor T allele whereas 18/29 patients showed homozygosity for the major C allele. Interestingly, we observed significantly better metabolic response in PHL patients carrying the rs12917 C allele resulting in a lower frequency of radiotherapy indication. CONCLUSION: MGMT polymorphism rs12917 seems to affect chemotherapy response in PHL. The prognostic value of this polymorphism should be investigated in a larger patient cohort.

18F-FDG-PET Detects Drastic Changes in Brain Metabolism in the Tg4-42 Model of Alzheimer's Disease.

The evaluation of new therapeutic strategies in Alzheimer's disease (AD) relies heavily on in vivo imaging and suitable animal models that mimic the pathological changes seen in patients. 18F-Fluorodeoxyglucose (18F-FDG)-positron-emission tomography (PET) is a well-established non-invasive imaging tool for monitoring changes in cerebral brain glucose metabolism in vivo. 18F-FDG-PET is used as a functional biomarker for AD as patients show an early and progressive reduction of cerebral glucose metabolism. However, earlier studies in preclinical models of AD showed conflicting results. The aim of this study was the evaluation of cerebral glucose metabolism in the Tg4-42 mouse model of AD using 18F-FDG-PET/magnetic resonance imaging (MRI). Tg4-42 mice show an age-dependent reduction in glucose metabolism together with severe neuron loss and memory deficits. Similar to AD patients early decrease in 18F-FDG uptake was already detected in young (3 months) Tg4-42 mice. The altered glucose metabolism coupled with age- and disease related cognitive decline of Tg4-42 mice make it a well-suited model for preclinical testing of AD-relevant therapeutics.