Effect of Peptide Dose on Radiation Dosimetry for Peptide Receptor Radionuclide Therapy with 177Lu-DOTATOC: A Pilot Study

Vikas Prasad; Sonal Prasad; Wencke Lehnert; Winfried Brenner; Huang Kai; Marcus Bronzel; Andreas Kluge

doi:10.4103/ijnm.ijnm_15_21

Effect of Peptide Dose on Radiation Dosimetry for Peptide Receptor Radionuclide Therapy with ¹⁷⁷Lu-DOTATOC: A Pilot Study

Indian J Nucl Med. 2021 Oct-Dec;36(4):412-421. doi: 10.4103/ijnm.ijnm_15_21. Epub 2021 Dec 15.

Authors

Vikas Prasad^{1

2

3}, Sonal Prasad^{1

4}, Wencke Lehnert^{5

6}, Winfried Brenner^{1

3

4}, Huang Kai¹, Marcus Bronzel⁵, Andreas Kluge⁵

Affiliations

¹ Department of Nuclear Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.
² Department of Nuclear Medicine, University Hospital Ulm, Ulm, Berlin, Germany.
³ German Cancer Consortium (DKTK), Partner Site Berlin, Berlin, Germany.
⁴ Berlin Experimental Radionuclide Imaging Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.
⁵ ABX - CRO Advanced Pharmaceutical Services, Dresden, Germany.
⁶ Department of Nuclear Medicine, University Hospital Hamburg Eppendorf, Berlin, Germany.

Abstract

Background: Optimal peptide concentration in treatment with ¹⁷⁷Lu-DOTATOC/DOTATATE is a matter of debate. Most of the studies with peptide receptor radionuclide therapy mention peptide dose ranging between 100 and 250 μg. The aim of this is to identify possible differences in radiation-absorbed doses (D/Gy) to tumor and kidney as a function of the peptide mass dose in order to identify the most suitable peptide dose for treatment. The therapeutic index (D_tumor/D_kidneys) was assessed as a key parameter for the treatment response.

Materials and methods: Five patients with metastasized Grade 1 to Grade 2 neuroendocrine tumor were analyzed in this study. Patients (n = 4) received two cycles of treatment with intravenously injected ¹⁷⁷Lu-DOTATOC containing peptide mass doses of 200 μg and 90 μg, alternatively; one patient was treated with 90 μg peptide mass in both the therapy cycles. Whole-body (head to mid-thigh) three-dimensional single-photon emission computerized tomography (3D SPECT)/CT images were acquired at 1, 4, 24, 48, and 72 h following the injection of ¹⁷⁷Lu-DOTATOC. Attenuation correction for 3D SPECT images was performed using CT data acquired and fused with the SPECT data (SPECT/CT).

Results: Overall, 28 target lesions (liver n = 17, lung n = 4, lymph nodes n = 1, and bone n = 2) were analyzed after 1^st and 2^nd therapy cycles. Tumor normalized absorbed doses varied by a factor of 74 between 0.35 and 26 mGy/MBq. Averaged over all patients, a higher normalized mean tumor dose (10.51 mGy/MBq) was achieved for a peptide dose of 200 μg compared to 90 μg (4.58 mGy/MBq). Kidneys doses varied by a factor of up to 4 between patients (0.25-1.0 mGy/MBq) (independent of dose cycle and peptide dose) and by a factor of up to 2 between dose cycles. The mean kidney dose was 13.7% higher for the 90 μg peptide dose compared to 200 μg. Given the higher tumor dose, the mean therapeutic index of a 200 μg mass dose was considerably higher (16.95), compared to a 90 μg mass dose (9.63). This coincided with the observation, that lesion volume reduction was more pronounced after an initial treatment with a 200 μg mass dose. Biologically effective dose was only 5. 1%-19.3% higher than the absorbed dose for individual dose cycles.

Conclusions: Higher peptide dose of 200 μg appears to be more suitable than 90 μg in terms of tumor dose, kidney dose, and therapeutic index for treatment with ¹⁷⁷Lu-DOTATOC.

Keywords: 177Lu-DOTATOC; dosimetry; peptide mass; peptide receptor radionuclide therapy.