The salivary glands as a dose limiting organ of PSMA- targeted radionuclide therapy: A review of the lessons learnt so far

Heynickx, Nathalie; Herrmann, Ken; Vermeulen, Koen; Baatout, Sarah; Aerts, An

doi:10.1016/j.nucmedbio.2021.04.003

Cited by 60 publications

(77 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The reduction in gland function gradually increases at absorbed doses of 20-40 Gy with a strong reduction (usually by >75%) at >40-46 Gy [51,53]. However, a recent review by Heynickx et al [36] discussed the limited knowledge about the damage to the salivary glands by PSMA-targeted therapies and the causative mechanisms. One of the conclusions was that more studies including valid treatment-emergent dosimetry are necessary to obtain reliable dose-response relationships and to define dose limits for the salivary glands.…”

Section: Discussionmentioning

confidence: 99%

“…The parotid glands were used as a surrogate for salivary glands since these are considered to be particularly sensitive to radiation [36]. Delineation of the parotid glands was performed on a combined anterior-posterior calibrated WB image (result of the quantitative correction described above) using a slightly oversized region of interest (ROI) to include all relevant activity.…”

Section: Dosimetric Data Analysismentioning

confidence: 99%

“…In PSMA therapy, the kidneys are considered the main OAR, but the salivary glands should not be neglected either [35,36], whereas other organs such as the spleen and liver may not be considered as OAR. In contrast to previously published dosimetry data [37], lacrimal glands are not considered as OAR in clinical routine, also confirmed by recently published data [38].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Streamlined Schemes for Dosimetry of 177Lu-Labeled PSMA Targeting Radioligands in Therapy of Prostate Cancer

Kurth

Heuschkel

Tonn

et al. 2021

Cancers

View full text Add to dashboard Cite

(Background) Aim of this retrospective analysis was to investigate in mCRPC patients treated with [177Lu]Lu-PSMA-617 whether the absorbed dose (AD) in organs at risk (OAR, i.e., kidneys and parotid glands) can be calculated using simplified methodologies with sufficient accuracy. For this calculation, results and kinetics of the first therapy cycle were used. (Methods) 46 patients treated with 2 to 6 cycles of [177Lu]Lu-PSMA-617 were included. As reference (current clinical standard) full dosimetry of the OAR based on quantitative imaging (whole body scintigraphy and quantitative SPECT/CT at 2, 24, 48 and 72 h p.i.) for every cycle was used. Alternatively, two dosimetry schemes, simplified in terms of image acquisition and dose calculation, were established, both assuming nearly unchanged kinetics of the radiopharmaceutical for subsequent cycles. (Results) In general, for both OAR the simplified methods provided results that were consistent with the dosimetric reference method, both per cycle and in terms of cumulative AD. Best results were obtained when imaging was performed at 48 h p.i. in each of the subsequent cycles. However, both simplified methods tended to underestimate the cumulative AD. (Conclusion) Simplified dosimetry schemes are feasible to tailor multi-cycle [177Lu]Lu-PSMA-targeted therapies.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Dosimetric Data Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Streamlined Schemes for Dosimetry of 177Lu-Labeled PSMA Targeting Radioligands in Therapy of Prostate Cancer

Kurth

Heuschkel

Tonn

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…Uptake in the salivary glands is the dose-limiting factor during endoradiotherapy with small-molecule PSMA inhibitors, resulting in (partially reversible) xerostomia when applied with 177 Lu, and severe to persistent xerostomia when applied with 225 Ac [ 50 , 51 ]. The quality of life for patients can, therefore, be significantly impaired despite preventive strategies, e.g., injection of botulinum toxin, external cooling, or gustatory stimulation have been described [ 99 , 100 , 101 , 102 , 103 ]. The uptake mechanism of PSMA inhibitors in salivary glands has not been thoroughly investigated to date, a more comprehensive review concerning known mechanisms is described by Heynickx et al [ 103 ].…”

Section: Quality and Technical Improvements Of Psma Inhibitorsmentioning

confidence: 99%

Radiolabeled PSMA Inhibitors

Neels

Kopka

Liolios

et al. 2021

Cancers

View full text Add to dashboard Cite

PSMA has shown to be a promising target for diagnosis and therapy (theranostics) of prostate cancer. We have reviewed developments in the field of radio- and fluorescence-guided surgery and targeted photodynamic therapy as well as multitargeting PSMA inhibitors also addressing albumin, GRPr and integrin αvβ3. An overview of the regulatory status of PSMA-targeting radiopharmaceuticals in the USA and Europe is also provided. Technical and quality aspects of PSMA-targeting radiopharmaceuticals are described and new emerging radiolabeling strategies are discussed. Furthermore, insights are given into the production, application and potential of alternatives beyond the commonly used radionuclides for radiolabeling PSMA inhibitors. An additional refinement of radiopharmaceuticals is required in order to further improve dose-limiting factors, such as nephrotoxicity and salivary gland uptake during endoradiotherapy. The improvement of patient treatment achieved by the advantageous combination of radionuclide therapy with alternative therapies is also a special focus of this review.

show abstract

“…The organs at risk in the case of EBRT are those closest to the tumour, whereas MRT toxicity depends on the pharmacokinetics of the radiopharmaceutical and its pattern of accumulation in normal organs. For example, dry mouth is a common side-effect of [ 177 Lu]Lu-PSMA ligands as they concentrate in the salivary glands [15]. In general, normal organs that are vulnerable following MRT are organs of excretion, particularly the kidneys, and the bone marrow, which may be irradiated as the radiopharmaceutical circulates freely post-injection [16,17].…”

Section: Normal Tissue Protectionmentioning

confidence: 99%

Combining External Beam Radiation and Radionuclide Therapies: Rationale, Radiobiology, Results and Roadblocks

et al. 2021

View full text Add to dashboard Cite

The emergence of effective radionuclide therapeutics, such as radium-223 dichloride, [ 177 Lu]Lu-DOTA-TATE and [ 177 Lu]Lu-PSMA ligands, over the last 10 years is driving a rapid expansion in molecular radiotherapy (MRT) research. Clinical trials that are underway will help to define optimal dosing protocols and identify groups of patients who are likely to benefit from this form of treatment. Clinical investigations are also being conducted to combine new MRT agents with other anticancer drugs, with particular emphasis on DNA repair inhibitors and immunotherapeutics. In this review, the case is presented for combining MRT with external beam radiotherapy (EBRT). The technical and dosimetric challenges of combining two radiotherapeutic modalities have impeded progress in the past. However, the need for research into the specific radiobiological effects of radionuclide therapy, which has lagged behind that for EBRT, has been recognised. This, together with innovations in imaging technology, MRT dosimetry tools and EBRT hardware, will facilitate the future use of this important combination of treatments.

show abstract

The salivary glands as a dose limiting organ of PSMA- targeted radionuclide therapy: A review of the lessons learnt so far

Cited by 60 publications

References 99 publications

Streamlined Schemes for Dosimetry of 177Lu-Labeled PSMA Targeting Radioligands in Therapy of Prostate Cancer

Streamlined Schemes for Dosimetry of 177Lu-Labeled PSMA Targeting Radioligands in Therapy of Prostate Cancer

Radiolabeled PSMA Inhibitors

Combining External Beam Radiation and Radionuclide Therapies: Rationale, Radiobiology, Results and Roadblocks

Contact Info

Product

Resources

About