CD70-Targeted Immuno-PET/CT for Detecting Heterogeneous CD70 Expression in Lymphomas: A Pilot Clinical Study

CD70 represents a promising therapeutic target for lymphoma. The expression patterns of CD70 and the diagnostic value of CD70-targeted immuno-PET/CT in lymphomas remain unknown. <b>Methods:</b> We investigated CD70 expression and explored the diagnostic value of CD70-targeted immuno-PET/CT in 154 patients with lymphoma. <b>Results:</b> Analysis of 154 lymphoma specimens showed CD70 positivity in 97 patients (63%), with a trend toward higher expression in older patients (<i>P</i> = 0.0014) and a possible inverse relationship with levels of B-cell lymphoma 6 (<i>P</i> = 0.001). In an ongoing clinical trial (NCT06852638), 20 patients with lymphoma underwent CD70-targeted immuno-PET/CT. The mean SUV_max of the CD70-targeted tracer was 3.4 ± 2.9 in 189 lymphoma lesions, significantly higher than that of the liver, spleen, and blood vessels (<i>P</i> < 0.01 for all). However, tracer uptake showed subtype-dependent variation, with diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue lymphoma exhibiting the highest tracer uptake. No significant difference emerged between nodal and extranodal lesions (<i>P</i> = 0.319). The tracer uptake correlated well with CD70 expression (<i>r</i> = 0.6655, <i>P</i> < 0.0001). Moreover, CD70-targeted immuno-PET/CT showed noninferior diagnostic performance compared with [¹⁸F]FDG across all evaluated categories, achieving detection rates of 100% for extranodal lesions and 97.7% for lymph node lesions and improving the detection of intracranial lesions. CD70-targeted immuno-PET/CT effectively monitored the therapeutic responses in 4 patients. <b>Conclusion:</b> CD70-targeted immuno-PET/CT effectively visualizes CD70 expression in patients with lymphoma, potentially serving as a valuable tool for improving CD70-targeted therapies.