Radiation Dosimetry in 177Lu-PSMA-617 Therapy
Details
Publication Year 2022-03,Volume 52,Issue #2,Page 243-254
Journal Title
Seminars in Nuclear Medicine
Publication Type
Review
Abstract
Radionuclide therapy using the small molecule PSMA bound to the beta-emitting radionuclide, Lutetium-177 ((177)Lu-PSMA) has demonstrated efficacy and survival benefit castrate resistant metastatic disease and represents a novel new line of therapy. Whilst dosimetry was critical for early development, it was not incorporated into either the TheraP or VISION randomized studies, highlighting the difficulty of adopting dosimetry in routine clinical practice. Accumulated clinical experience has also shown that the common (and generally low grade) toxicities such as nausea, xerostomia, and cytopenias are not readily predicted on the basis of dosimetry estimates. The majority of dosimetry and clinical literature deals with the radiopharmaceutical (177)Lu-PSMA-617 which displays relatively consistent patterns of retention among normal tissues and high specificity for metastatic prostate cancer phenotypes. Population dosimetry incorporating estimates to the kidneys, salivary glands, and bone marrow have been widely reported the typical range of doses is becoming well established. There is growing interest on tumor dosimetry in (177)Lu-PSMA-617 therapy as an overall modest side-effect profile from primary organ retention has been observed. A focus away from normal organ dosimetry to whole body tumor dosimetry may enable early prediction of treatment failure. Given the safety of (177)Lu-PSMA there is also potential to escalate administered radioactivity to further improve outcomes. Importantly, the variability of uptake between individuals, both to tumor and normal organs, has also been highlighted which provides some rationale for the utility of personalized radiation analysis to optimize treatment based on potential toxicity thresholds or tumor control. Methods to perform dosimetry using serial post treatment imaging may incorporate planar, 3D SPECT, or hybrid datasets. Reliable measurements may be obtained through either method, however, continued developments in computational analysis are better suited to fully 3D imaging; particularly in conjunction with volumetric CT to assist with alignment and contouring. Dose analysis over sequential treatment cycles is vital to understand the radiobiology of these treatments which is unique compared to external beam therapy due to dose rate, fractionation scheme, and potential for intratumoral nonuniformity.
Keywords
Dipeptides; Heterocyclic Compounds, 1-Ring/therapeutic use; Humans; Male; Prostate-Specific Antigen; *Prostatic Neoplasms, Castration-Resistant/diagnostic; imaging/metabolism/radiotherapy; Radioisotopes; Radiometry; Radiopharmaceuticals/therapeutic use
Department(s)
Cancer Imaging
PubMed ID
34893320
Terms of Use/Rights Notice
Refer to copyright notice on published article.


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