Dosimetry in safety assessment of elevated pulmonary doses from radionuclide therapies

Sanchay Jain; Yusuf Menda; Stephen Graves

Introduction: Radionuclide therapies are generally considered safe from the point of view of lung radiation exposure, however, elevated lung absorbed dose may result from pulmonary metastases and in some benign chronic lung diseases. Although external beam radiotherapy-derived lung dose limits are available, extrapolation to multi-cycle therapy may not accurately predict dose-effects. Similarly, lung dosimetry is crucial in the planning of liver-directed transarterial radioembolization (TARE) using Yttrium-90 labeled microspheres. Here we present three patient cases with concern for high lung exposure who underwent systemic radionuclide therapies with dosimetry, and one patient who underwent sequential TARE procedures resulting in cumulative lung dose in excess of the commonly accepted 50 Gy limit. Methods: Retrospective review of the dosimetric analysis and follow up of four patients who underwent therapy with [177Lu] Lu-PSMA-617, [177Lu] Lu-DOTATATE, [131I] NaI, and [90Y] SIR-Spheres was done. In all cases the patients received greater than typical cumulative lung doses for their respective therapeutic agents. The dosimetric analysis was done using manual contouring and time-activity curve integration, followed by dose calculation using commercially-available software. Results: 1. A 73-year-old-male with a history of papillary thyroid cancer treated with thyroidectomy and [131I] NaI therapy 19 years ago (therapeutic activity currently unknown) presented with diffuse iodine avid metastases to the lungs underwent pretreatment imaging and dosimetry with [131I] NaI. Lung uptake was measured to be 45% at 48 hours post-administration. Lung dosimetry indicated a pulmonary dose of 28.6 cGy/mCi, corresponding to a therapeutic [131I] NaI activity limit of 105 mCi to avoid exceeding 30 Gy to the lungs. He subsequently underwent [131I] NaI therapy with 90 mCi, corresponding to a pulmonary dose of 25.7 Gy. The patient did not have significant pulmonary adverse effects following therapy. 2. A 65-year old male with metastatic castration-resistant prostate cancer and a history of occupational lung disease had diffusely increased PSMA uptake in both lungs on the pre-therapy [68Ga] Ga-PSMA-11 PET/CT scan. He underwent 4 cycles of [177Lu] Lu-PSMA-617 therapy (7.4 GBq/cycle) with post-therapy dosimetry performed for cycles 1-3. Dosimetry following cycles 1, 2, and 3 revealed lung doses of 7.5 Gy, 4.2 Gy, and 3.4 Gy, respectively, for an estimated cumulative lung dose of ~18 Gy for all four cycles of therapy. No adverse pulmonary effects were observed within a 5 month follow-up window. 3. A 71-year-old male with hepatic metastases from renal cell carcinoma underwent seven liver directed radioembolization therapies over a period of 4 years. The estimated lung doses (and lung shunt fractions) of 6.9 Gy (13%), 8.0 Gy (10.6%), 9.3 Gy (10.8%), 3.7 Gy (2.3%), 2.8 Gy (3.5%), 30.1 Gy (21%), and 13.8 Gy (18%) were observed for the treatments 1,2,3,4,5,6 and 7, respectively. The estimated cumulative lung dose was ~75 Gy. No significant pulmonary adverse effects were observed during 1.5 years of follow up. 4. An 81-year-old female with well differentiated neuroendocrine tumor of midgut origin with diffuse pulmonary metastases underwent treatment with [177Lu] Lu-DOTATATE and post therapy dosimetry revealed an estimated lung dose (entire lung volume including disease) of 6.7 Gy from the first 7.4 GBq administration of [177Lu] Lu-DOTATATE. For comparison, the average lung dose over four cycles of [177Lu] Lu-DOTATATE is typically ~0.9 Gy per the FDA package insert. Conclusions: Elevated lung exposure from radionuclide therapies can result from metastatic disease (cases 1 and 4) or due to benign chronic lung disease (case 2). Additional data regarding lung dose-effect relationships may help inform optimal management of patients with high radionuclide lung uptake.

Dosimetry in safety assessment of elevated pulmonary doses from radionuclide therapies

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