Tumor-Avid 3-(1'-Hexyloxy)ethyl-3-devinylpyrpyropheophorbide-a (HPPH)-3Gd(III)tetraxetan (DOTA) Conjugate Defines Primary Tumors and Metastases.

3-(1'-Hexyloxyethyl)-3-devinylpyropheophorbide-a (HPPH or Photochlor), a tumor-avid chlorophyll a derivative currently undergoing human clinical trials, was conjugated with mono-, di-, and tri-Gd(III)tetraxetan (DOTA) moieties. The T1/T2 relaxivity and in vitro PDT efficacy of these conjugates were determined. The tumor specificity of the most promising conjugate was also investigated at various time points in mice and rats bearing colon tumors, as well as rabbits bearing widespread metastases from VX2 systemic arterial disseminated metastases. All the conjugates showed significant T1 and T2 relaxivities. However, the conjugate containing 3-Gd(III)-aminoethylamido-DOTA at position 17 of HPPH demonstrated great potential for tumor imaging by both MR and fluorescence while maintaining its PDT efficacy. At an MR imaging dose (10 µmol/kg), HPPH-3Gd(III)DOTA did not cause any significant organ toxicity in mice, indicating its potential as a cancer imaging (MR and fluorescence) agent with an option to treat cancer by photodynamic therapy (PDT).

Identification and Validation of Radiographic Enhancement for Reliable Differentiation of CD117(+) Benign Renal Oncocytoma and Chromophobe Renal Cell Carcinoma.

Purpose: The diagnostic differential for CD117/KIT(+) oncocytic renal tumor biopsies is limited to benign renal oncocytoma versus chromophobe renal cell carcinoma (ChRCC); however, further differentiation is often challenging and requires surgical resection. We investigated clinical variables that might improve preoperative differentiation of CD117(+) renal oncocytoma versus ChRCC to avoid the need for benign tumor resection.Experimental Design: A total of 124 nephrectomy patients from a single institute with 133 renal oncocytoma or ChRCC tumors were studied. Patients from 2003 to 2012 comprised a retrospective cohort to identify clinical/radiographic variables associated with renal oncocytoma versus ChRCC. Prospective validation was performed among consecutive renal oncocytoma/ChRCC tumors resected from 2013 to 2017.Results: Tumor size and younger age were associated with ChRCC, and multifocality with renal oncocytoma; however, the most reliable variable for ChRCC versus renal oncocytoma differentiation was the tumor:cortex peak early-phase enhancement ratio (PEER) using multiphase CT. Among 54 PEER-evaluable tumors in the retrospective cohort [19 CD117(+), 13 CD117(-), 22 CD117-untested], PEER classified each correctly as renal oncocytoma (PEER >0.50) or ChRCC (PEER ≤0.50), except for four misclassified CD117(-) ChRCC variants. Prospective study of PEER confirmed 100% accuracy of renal oncocytoma/ChRCC classification among 22/22 additional CD117(+) tumors. Prospective interobserver reproducibility was excellent for PEER scoring (intraclass correlation coefficient, ICC = 0.97) and perfect for renal oncocytoma/ChRCC assignment (ICC = 1.0).Conclusions: In the largest clinical comparison of renal oncocytoma versus ChRCC to our knowledge, we identified and prospectively validated a reproducible radiographic measure that differentiates CD117(+) renal oncocytoma from ChRCC with potentially 100% accuracy. PEER may allow reliable biopsy-based diagnosis of CD117(+) renal oncocytoma, avoiding the need for diagnostic nephrectomy. Clin Cancer Res; 24(16); 3898-907. ©2018 AACR.

Sensitivity and specificity of a CAD solution for lung nodule detection on chest radiograph with CTA correlation.

The objective of this research was to determine the sensitivity and specificity of a commercially available computer-aided detection (CAD) system for detection of lung nodule on posterior-anterior (PA) chest radiograph in a varied patient population who are referred to computed tomographic angiogram (CTA) of the chest as a reference standard. Patients who had a PA chest radiograph with concomitant CTA of the chest were included in this retrospective study. The PA chest radiograph was analyzed by a CAD device, and results were recorded. A qualitative assessment of the CAD results was performed using a 5-point Likert scale. The CTA was then reviewed to determine if there were correlative nodules. The presence of a correlative nodule between 0.5 cm and 1.5 cm was considered a positive result. The baseline sensitivity of the system was determined to be 0.707 (95% CI = 0.52-0.86), with a specificity of 0.50 (95% CI = 0.38-0.76). Positive predictive value was 0.30 (95% CI = 0.24-0.49), with a negative predictive value of 0.858 (95% CI = 0.82-0.95), and accuracy of 0.555 (95% CI = 0.40-0.66). When excluding nodules that were qualitatively determined by a thoracic radiologist to be false positives, the specificity was 0.781 (95% CI = 0.764-0.839), the positive predictive value was 0.564 (95% CI = 0.491-0.654), the negative predictive value was 0.829 (95% CI = 0.819-0.878), and the accuracy was 0.737 (95% CI = 0.721-0.801). The use of CAD for lung nodule detection on chest radiograph, when used in conjunction with an experienced radiologist, has a very good sensitivity, specificity, and accuracy.