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Purpose: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging has impacted the management of patients with prostate cancer (PCa) in many parts of the world. PSMA-targeted endoradiotherapies are also being increasingly utilized and for these applications, the radiopharmaceutical distribution in normal organs is particularly important because it may limit the dose that can be delivered to tumors. In this study, we measured both interpatient and intrapatient variability of [ 18 F]DCFPyL uptake in the most relevant normal organs., Procedures: Baseline and 6-month follow-up PSMA-targeted [ 18 F]DCFPyL PET/computed tomography (CT) scans from 39 patients with PCa were reviewed. Volumes of interest were manually drawn using the best visual approximation of the organ edge for both lacrimal glands, all four major salivary glands, the liver, the spleen, and both kidneys for all patients. The average SUV mean , the COVs, and intraclass correlation coefficients (ICCs) across scans were calculated. Bland-Altman analyses were performed for all organs to derive repeatability coefficients (RCs)., Results: The liver demonstrated the lowest interpatient variability (13.0 and 16.6 % at baseline and follow-up, respectively), while the spleen demonstrated the largest interpatient variability (44.6 and 51.0 % at baseline and follow-up, respectively). The lowest intrapatient variability was found in the spleen (ICC 0.86) while the highest intrapatient variability was in the kidneys (ICCs 0.40-0.50). Bland-Altman analyses showed 95 % repeatability coefficients for mean uptake > 40 % for multiple organs and were highest for the lacrimal glands, kidneys, and spleen., Conclusions: Normal organs demonstrate significant variability in uptake of the PSMA-targeted radiotracer [ 18 F]DCFPyL. Depending on the organ, different contributions of interpatient and intrapatient factors affect the intrinsic variability. The RCs also vary significantly among the different organs were highest for the lacrimal glands, kidneys, and spleen. These findings may have important implications for the design of clinical protocols and personalized dosimetry for PSMA-targeted endoradiotherapies.

The dose-limiting salivary gland toxicity of 225 Ac-labelled PSMA for treatment of metastatic, castration-resistant prostate cancer remains unresolved. Suppressing the metabolism of the gland by intraparenchymal injections of botulinum toxin appears to be a promising method to reduce off-target uptake. A 68 Ga-PSMA PET/CT scan performed 45 days after injection of 80 units of botulinum toxin A into the right parotid gland in a 63-year-old patient showed a decrease in the SUVmean in the right parotid gland of up to 64% as compared with baseline. This approach could be a significant breakthrough for radioprotection of the salivary glands during PSMA radioligand therapy., Competing Interests: Compliance with Ethical StandardsRichard P. Baum, Thomas Langbein, Aviral Singh, Mostafa Shahinfar, Christiane Schuchardt, Gerd Fabian Volk, Harshad Kulkarni declare that they have no conflict of interest.All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the1964 Declaration of Helsinki and its later amendments or comparable ethical standards.Informed consent was obtained from the patient who was the subject of the study.

Purpose: To explore feasibility, tolerability, dosimetry and probable efficacy of intravenous endoradiotherapy with carrier-added 4-[(131)I]iodo-L-phenylalanine (c.a. (131)I-IPA) in refractory high-grade glioma., Methods: Two male patients (45 and 50 years), with long-standing, extensively pre-treated gliomas and evidence of progression underwent single intravenous injections of 2 and 4 GBq of c.a. (131)I-IPA, respectively. Tumour targeting was verified by (131)I-IPA single-photon emission computed tomography (SPECT). Metabolic and morphological changes indicative of tumour response were assessed by sequential [(18)F]fluoroethyltyrosine ((18)F-FET) positron emission tomography (PET) and contrast-enhanced magnetic resonance imaging (MRI) following therapy. Further monitoring included clinical state, safety laboratory, quality of life and dosimetry. Absorbed mean organ and whole-body doses were determined according to the Medical Internal Radiation Dose (MIRD) scheme using OLINDAEXM based on serial planar scintigraphy., Results: Both patients tolerated the treatment well. No evidence of acute or delayed organ toxicity was observed. (131)I-IPA accumulated in the tumour recurrences identified by MRI/(18)F-FET. In patient 1, PET showed progressively decreasing maximum standardised uptake values (SUVmax) over 10 months, indicating metabolic response, paralleled by reduced contrast enhancement and tumour volume on MRI. Progression occurred 18 months after therapy. Treatment was repeated using 6.6 GBq of (131)I-IPA, to which no response was observed. Patient 2, followed-up for 3 months after therapy, showed stable disease on MRI and PET. Mean absorbed whole body doses ranged from 0.13 to 0.17 mSv/MBq, with the highest absorbed organ doses to kidneys, bladder and heart (0.86-1.23; 0.49-0.6 and 0.45-0.56 mSv/MBq)., Conclusion: Systemic endoradiotherapy using up to 6.6 GBq of c.a.(131)I-IPA is not associated with clinically detectable toxicity. Measurable anti-tumour effects in gliomas were observed. (131)I-IPA warrants further evaluation as glioma therapy.