A First-in-Human Study of ⁶⁸Ga-Nanocolloid PET/CT Sentinel Lymph Node Imaging in Prostate Cancer Demonstrates Aberrant Lymphatic Drainage Pathways

Abstract

Our goal was to assess the feasibility, safety, and utility of a novel Ga-nanocolloid radiotracer with PET/CT lymphoscintigraphy for identification of sentinel lymph nodes (SLNs). This was a pilot study of patients from a tertiary cancer hospital who required insertion of gold fiducials for prostate cancer radiation therapy. Participation did not affect cancer management. Ultrasound-guided transperineal intraprostatic injection of a PET tracer (iron oxide nanocolloid labeled with Ga) was performed after placement of the fiducials. PET/CT lymphoscintigraphy imaging took place at approximately 45 and 100 min after injection of the tracer. The study was monitored using a Bayesian design with the assumption that at least 1 SLN could be identified in at least two thirds of cases with more than 80% confidence. SLN identification was successful in all 5 participants, allowing completion of the pilot study as per protocol. No adverse effects were observed. Unexpected potential pathways for transit of malignant cells, as well as the expected regional drainage pathways, were discovered. Rapid tracer drainage to pelvic bone, perivesicular, mesorectal, inguinal, and Virchow nodes was identified. SLN identification usingGa-nanocolloid PET/CT can be successfully performed. Nontraditional pathways of disease spread were identified, including drainage to pelvic bone and to perivesicular, mesorectal, inguinal, and Virchow nodes. The prevalence of both aberrant and nonlymphatic pathways of spread should be further investigated with this technique.

99mTc-68Ga-ICG-Labelled Macroaggregates and Nanocolloids of Human Serum Albumin: Synthesis Procedures of a Trimodal Imaging Agent Using Commercial Kits

“…In addition, the nonquantitative nature of fluorescence emission is an further impediment when using ICG as a single tracer. Furthermore, in other body regions such as head and neck or pelvic area, where lymphatic drainage shows wide interpatient variability, additional problems are involved [27,28].…”

Haute Couture or Ready-To-Wear? Tailored Pelvic Radiotherapy for Prostate Cancer Based on Individualized Sentinel Lymph Node Detection

“…More recently, Doughton et al used intra-prostatic injection of Gallium-68 labeled nanocolloids for PET-CT detection of SLNs outside the usual drainage areas in an attempt to increase the detection sensitivity of the lymph nodes. The authors then showed that while the lymph node drainage pattern was similar to the usual techniques for detecting SLNs, it was faster, making it possible to detect aberrant non-lymphatic pathways, most notably venous [26]. Similarly, Prostate Specific Membrane Antigen (PSMA) PET showed that the common iliac nodes are a frequent site of both occult disease and recurrence following local treatment [27].…”

Utility of Lymphadenectomy in Prostate Cancer: Where do We Stand?

“…Doughton et al investigated the first-in-human usage of 68 Ga-Nanocolloid as the radiotracer for PET/CT lymphoscintigraphy and its results were promising though this technique of SLN imaging requires further research. What's interesting is discovering unexpected lymph drainage patterns including pathways leading to perivesicular, mesorectal, inguinal and Virchow nodes [85]. Another innovative technique engages prostate specific membrane antigen -PSMA-labeled radiotracer (111In-PSMA-I&T).…”