A New Era in Imaging with ImmunoPET – Accurate Diagnosis in Kidney Cancer

Kidney Cancer: Diagnostic Challenges and Current Approaches

The most common type of kidney cancer, clear-cell renal cell carcinoma (RCC), accounts for 90% of all kidney cancer deaths but can be difficult to diagnose. It cannot easily be distinguished from other renal masses using standard imaging tools such as computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound. Blood tests such as liquid biopsies are also inadequate for ruling it out. Most patients with suspected RCC are therefore referred directly for surgery without a diagnostic biopsy.

As a result of diagnostic uncertainty, many patients with small but benign or slow-growing tumors undergo unnecessary surgery. This poses more serious risks, particularly for older people and those with comorbidities. Long postoperative recovery periods and complications create major problems for this group. More accurate diagnostic methods could help these patients avoid unnecessary surgery.

ImmunoPET: A New Diagnostic Approach

In recent years, ImmunoPET imaging, used in nuclear medicine, has revolutionized the management of prostate and neuroendocrine cancers in particular. Researchers are investigating its application to kidney cancer diagnosis. Its greatest advantage is the ability to detect cancer cells with high sensitivity and specificity by binding to specific biomarkers on the cell surface.

One of the latest developments is the use of a radioactive antibody targeting a cell-surface marker called carbonic anhydrase 9 (CAIX): [89Zr]Zr-girentuximab is the antibody used in this approach.

The cell-surface molecule CAIX is a biomarker overexpressed in clear-cell RCC. Clinical studies have shown that this method can successfully distinguish kidney cancer from other renal masses.

Findings of the [89Zr]Zr-Girentuximab Study

A research group led by Dr. Brian Shuch conducted a prospective, open-label, multicenter phase 3 clinical trial involving 300 patients with renal masses smaller than 7 cm. The results can be summarized as follows:

• Sensitivity: 85.5% (95% CI: 81.5%–89.6%)
• Specificity: 87.0% (95% CI: 81.0%–93.1%)
• Positive Predictive Value: 93%
• All false-positive tumors were associated with other malignancies (such as papillary carcinoma).

Unnecessary Operations Could Be Avoided

These findings show that ImmunoPET could not only diagnose RCC but also substantially reduce unnecessary biopsies and surgery. Whole-body scanning for CAIX expression has also been proposed as a means of staging RCC and detecting metastatic spread.

Practical Benefits for Patient Management

ImmunoPET may prevent inappropriate treatment decisions, particularly in young patients with small lesions. For example, an ImmunoPET scan in a young woman correctly identified a fat-poor angiomyolipoma, a benign tumor. She avoided unnecessary surgery and could continue her life knowing that treatment would be needed only if the tumor became large.

The images below present four patient examples demonstrating the effectiveness of [89Zr]Zr-girentuximab PET-CT for diagnosing renal lesions. They show each patient's diagnostic CT (left), PET (middle) and fused PET-CT images (right), with arrows indicating the lesions.

Explanation:

1. Case (A):

   • Patient: A 40-year-old man.
   • Lesion: A 12 mm lesion in the upper region of the right kidney.
   • PET Result: Positive [89Zr]Zr-girentuximab PET.
   • Histopathology: Confirmed as clear-cell renal cell carcinoma (RCC).

2. Case (B):

   • Patient: A 53-year-old woman.
   • Lesion: A 62 mm lesion in the middle of the left kidney.
   • PET Result: Negative [89Zr]Zr-girentuximab PET.
   • Histopathology: Confirmed as a benign lesion.

3. Case (C):

   • Patient: A 63-year-old woman.
   • Lesion: A 62 mm lesion in the middle of the right kidney.
   • PET Result: Negative [89Zr]Zr-girentuximab PET.
   • Histopathology: Confirmed as papillary renal cell carcinoma (malignant).

4. Case (D):

   • Patient: A 59-year-old woman.
   • Lesion: A 57.5 mm lesion in the left kidney.
   • PET Result: Negative [89Zr]Zr-girentuximab PET.
   • Histopathology: Confirmed as clear-cell renal cell carcinoma.

These images highlight the ability of [89Zr]Zr-girentuximab PET to characterize renal tumors and its diagnostic limitations. In particular, some malignant lesions (cases C and D) were PET-negative, indicating limitations associated with the CAIX marker. By contrast, the positive PET result in case A enabled a highly accurate diagnosis of RCC.

Future Prospects and Theranostic Approaches

Radioactive antibodies such as [89Zr]Zr-girentuximab open the door to theranostic applications that may serve both diagnostic and therapeutic purposes. Radiotherapies targeting CAIX can destroy cancer cells by delivering a high radiation effect to cells expressing this molecule. This approach may offer new possibilities for treating metastatic RCC.

ImmunoPET and the Future of Standard Care

If this technology receives FDA approval, ImmunoPET is expected to become a new standard for kidney cancer diagnosis. Given the limitations of current imaging and biopsy methods, [89Zr]Zr-girentuximab will improve healthcare efficiency and patient outcomes through early, definitive diagnosis of RCC.