Medical application of rapid prototyping is feasible for specialized surgical planning and prosthetics applications and has significant potential for development of new medical applications.

The recent development of quinoline-based PET tracers that act as fibroblast-activation-protein inhibitors (FAPIs) demonstrated promising preclinical and clinical results. FAP is overexpressed by cancer-associated fibroblasts of several tumor entities. Here, we quantify the tumor uptake on 68 Ga-FAPI PET/CT of various primary and metastatic tumors to identify the most promising indications for future application. Methods: 68 Ga-FAPI PET/CT scans were requested by various referring physicians according to individual clinical indications that were considered insufficiently covered by 18 F-FDG PET/CT or other imaging modalities. All PET/CT was performed 1 h after injection of 122-312 MBq of 68 Ga-FAPI-04. We retrospectively identified 80 patients with histopathologically proven primary tumors or metastases or radiologically unequivocal metastatic lesions of histologically proven primary tumors. Tumor uptake was quantified by SUV max and SUV mean (60% isocontour). Results: Eighty patients with 28 different tumor entities (54 primary tumors and 229 metastases) were evaluated. The highest average SUV max (.12) was found in sarcoma, esophageal, breast, cholangiocarcinoma, and lung cancer. The lowest 68 Ga-FAPI uptake (average SUV max , 6) was observed in pheochromocytoma, renal cell, differentiated thyroid, adenoid cystic, and gastric cancer. The average SUV max of hepatocellular, colorectal, head-neck, ovarian, pancreatic, and prostate cancer was intermediate . SUV varied across and within all tumor entities. Because of low background in muscle and blood pool (SUV max , 2), the tumor-to-background contrast ratios were more than 3-fold in the intermediate and more than 6fold in the high-intensity uptake group. Conclusion: Several highly prevalent cancers presented with remarkably high uptake and image contrast on 68 Ga-FAPI PET/CT. The high and rather selective tumor uptake may open up new applications for noninvasive tumor characterization, staging examinations, or radioligand therapy. ://jnm.snmjournals.org/content/60/6/801 This article and updated information are available at: http://jnm.snmjournals.org/site/subscriptions/online.xhtml Information about subscriptions to JNM can be found at: http://jnm.snmjournals.org/site/misc/permission.xhtml

PurposeSince the introduction of positron emission tomography (PET) imaging with 68Ga-PSMA-HBED-CC (=68Ga-DKFZ-PSMA-11), this method has been regarded as a significant step forward in the diagnosis of recurrent prostate cancer (PCa). However, published data exist for small patient cohorts only. The aim of this evaluation was to analyse the diagnostic value of 68Ga-PSMA-ligand PET/CT in a large cohort and the influence of several possibly interacting variables.MethodsWe performed a retrospective analysis in 319 patients who underwent 68Ga-PSMA-ligand PET/CT from 2011 to 2014. Potential influences of several factors such as prostate-specific antigen (PSA) level and doubling time (DT), Gleason score (GSC), androgen deprivation therapy (ADT), age and amount of injected tracer were evaluated. Histological verification was performed in 42 patients after the 68Ga-PSMA-ligand PET/CT. Tracer uptake was measured in 901 representative tumour lesions.ResultsIn 82.8 % of the patients at least one lesion indicative of PCa was detected. Tumor-detection was positively associated with PSA level and ADT. GSC and PSA-DT were not associated with tumor-detection. The average maximum standardized uptake value (SUVmax) of tumour lesions was 13.3 ± 14.6 (0.7–122.5). Amongst lesions investigated by histology, 30 were false-negative in 4 different patients, and all other lesions (n = 416) were true-positive or true-negative. A lesion-based analysis of sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) revealed values of 76.6 %, 100 %, 91.4 % and 100 %. A patient-based analysis revealed a sensitivity of 88.1 %. Of 116 patients available for follow-up, 50 received local therapy after 68Ga-PSMA-ligand PET/CT.Conclusion68Ga-PSMA-ligand PET/CT can detect recurrent PCa in a high number of patients. In addition, the radiotracer is highly specific for PCa. Tumour detection is positively associated with PSA and ADT. 68Ga-PSMA-ligand PET/CT can help delay systemic therapy of PCa.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-014-2949-6) contains supplementary material, which is available to authorized users.

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The biodistribution of the novel (68)Ga-PSMA tracer and its ability to detect PC lesions was analysed in 37 patients. Within healthy organs, kidneys and salivary glands demonstrated the highest radiotracer uptake. Lesions suspicious for PC presented with excellent contrast as early as 1 h p.i. with high detection rates even at low PSA levels.

Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts and is involved in a variety of tumor-promoting activities such as matrix remodeling, angiogenesis, chemotherapy resistance, and immunosuppression. Because FAP shows low expression in most normal organs, it presents an interesting target for imaging and endoradiotherapy. In this investigation, FAP inhibitors (FAPIs) were modified and optimized for use as theranostic tracers. FAPIs based on a quinoline structure were synthesized and characterized with respect to binding, internalization, and efflux in cells expressing human and murine FAP as well as CD26. Preclinical pharmacokinetics were determined in tumor-bearing animals with biodistribution experiments and small-animal PET. Finally, a proof-of-concept approach toward imaging and therapy was chosen for 2 patients with metastasized breast cancer. Of 15 synthesized FAPIs, FAPI-04 was identified as the most promising tracer for clinical application. Compared with the previously published ligand, FAPI-02, FAPI-04 showed excellent stability in human serum, higher affinity for FAP as opposed to CD26, and slower excretion in vitro. In vivo, a higher SUV was reached in tumor-bearing animals, leading to larger areas under the curve as calculated from biodistribution experiments. Finally, PET/CT scans with Ga-FAPI-04 in 2 patients with metastasized breast cancer revealed high tracer uptake in metastases and a reduction in pain symptoms after therapy with a considerably low dose ofY-FAPI-04. FAPI-04 represents a promising tracer for both diagnostic imaging and, possibly, targeted therapy of malignant tumors with a high content of activated fibroblasts, such as breast cancer.

PurposePositron emission tomography (PET) with choline tracers has found widespread use for the diagnosis of prostate cancer (PC). However, choline metabolism is not increased in a considerable number of cases, whereas prostate-specific membrane antigen (PSMA) is overexpressed in most PCs. Therefore, a 68Ga-labelled PSMA ligand could be superior to choline tracers by obtaining a high contrast. The aim of this study was to compare such a novel tracer with standard choline-based PET/CT.MethodsThirty-seven patients with biochemical relapse of PC [mean prostate-specific antigen (PSA) 11.1 ± 24.1 ng/ml, range 0.01–116] were retrospectively analysed after 18F-fluoromethylcholine and 68Ga-PSMA PET/CT within a time window of 30 days. Radiotracer uptake that was visually considered as PC was semi-quantitatively analysed by measuring the maximum standardized uptake values (SUVmax) of the scans acquired 1 h after injection of 68Ga-PSMA complex solution (median 132 MBq, range 59–263 MBq) and 18F-fluoromethylcholine (median 237 MBq, range 114–374 MBq), respectively. In addition, tumour to background ratios were calculated.ResultsA total of 78 lesions characteristic for PC were detected in 32 patients using 68Ga-PSMA PET/CT and 56 lesions were detected in 26 patients using choline PET/CT. The higher detection rate in 68Ga-PSMA PET/CT was statistically significant (p = 0.04). In five patients no lesion was found with both methods. All lesions detected by 18F-fluoromethylcholine PET/CT were also seen by 68Ga-PSMA PET/CT. In 68Ga-PSMA PET/CT SUVmax was clearly (>10 %) higher in 62 of 78 lesions (79.1 %) and the tumour to background ratio was clearly (>10 %) higher in 74 of 78 lesions (94.9 %) when compared to 18F-fluoromethylcholine PET/CT.Conclusion68Ga-PSMA PET/CT can detect lesions characteristic for PC with improved contrast when compared to standard 18F-fluoromethylcholine PET/CT, especially at low PSA levels.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-013-2525-5) contains supplementary material, which is available to authorized users.

The aim of this guideline is to provide standards for the recommendation, performance, interpretation and reporting of Ga-PSMA PET/CT for prostate cancer imaging. These recommendations will help to improve accuracy, precision, and repeatability ofGa-PSMA PET/CT for prostate cancer essentially needed for implementation of this modality in science and routine clinical practice.