Specific Uptake in the Bone Marrow Causes High Absorbed Red Marrow Doses During [

Area of Science:

• Nuclear Medicine
• Radiopharmacology
• Medical Physics

Background:

• Bone marrow suppression is a frequent adverse effect of [177Lu]Lu-DOTATATE therapy for neuroendocrine neoplasms.
• Neuroendocrine neoplasms and CD34-positive hematopoietic progenitor cells share somatostatin receptor type 2 expression, potentially causing [177Lu]Lu-DOTATATE uptake in red marrow.
• Accurate dosimetry is crucial for understanding and mitigating treatment-related toxicities.

Purpose of the Study:

• To identify and quantify specific [177Lu]Lu-DOTATATE uptake in red marrow.
• To determine the absorbed radiation dose to red marrow in patients undergoing [177Lu]Lu-DOTATATE therapy.
• To compare red marrow dosimetry using a compartment model versus standard blood-based methods.

Main Methods:

• Seventeen patients with neuroendocrine neoplasms treated with [177Lu]Lu-DOTATATE underwent serial SPECT/CT imaging post-treatment.
• Activity concentrations were quantified in vertebrae (T9-L5) and hip bones, representing red marrow sites.
• A compartment model, using descending aorta activity as input, differentiated specific red marrow uptake from blood-based contributions for dosimetry.

Main Results:

• All patients showed increased [177Lu]Lu-DOTATATE uptake in vertebrae and hip bones compared to aortic concentrations.
• Specific red marrow uptake averaged 49% higher than non-specific uptake, with significant variability (0%-93%).
• Median absorbed doses to red marrow were 0.056 Gy/GBq (vertebrae) and 0.043 Gy/GBq (hip bones), with higher doses in patients with bone metastases.

Conclusions:

• Specific red marrow uptake of [177Lu]Lu-DOTATATE correlates with somatostatin receptor expression on hematopoietic progenitor cells.
• Standard blood-based dosimetry methods underestimate the absorbed dose to red marrow due to unaddressed prolonged specific uptake.
• Accurate red marrow dosimetry is essential for optimizing [177Lu]Lu-DOTATATE therapy and managing potential hematological toxicities.